omim_summarized_1.0.9.json

{"EHLERS-DANLOS SYNDROME, VASCULAR TYPE": "Clinical features of the rare genetic disorder, type IV Ehlers-Danlos syndrome (EDS), include bleeding and cardiac arrest following minor trauma, dilated endoplasmic reticulum in dermal fibroblasts, keloid formation, spontaneous pneumothorax and bowel rupture, acrogeric appearance of the skin, tight skin over the nose and ears, acroosteolysis, reduced synthesis of type III collagen, pulsating tinnitus, periorbital swelling, lax or thin skin with venous markings, telangiectases, rectal bleeding, hepatoportal fistula, microangiopathy of skin capillaries, joint contractures, cerebral vascular complications, hemothorax, arterial rupture, varicose vein surgery risk, congenital anomalies, increased wall stress in arteries, low intima-media thickness, pregnancy-related complications and deaths, aortic aneurysm/dissection/rupture, coronary artery aneurysm/dissection/rupture, carotid cavernous sinus fistulae, lethal cerebral vascular accidents, bowel perforations, and birth defects.", "SALT AND PEPPER DEVELOPMENTAL REGRESSION SYNDROME": "Rare genetic disorder: Autosomal recessive infantile-onset epilepsy syndrome with developmental stagnation, blindness, poor feeding, vomiting, failure to thrive, generalized tonic-clonic seizures, startle myoclonus, difficult seizure control, profound developmental stagnation, nonverbal, nonpurposeful arm movements, deteriorating visual function, optic atrophy, multifocal epileptiform discharges, diffuse brain atrophy, consanguineous French parents, delayed psychomotor development, severe mental retardation, dysmorphic facial features, pigmentary skin changes, choreoathetoid movements, hypotonic tetraparesis, visual impairment, cortical blindness, respiratory chain defect, hyperpigmented macules, depigmentation, severe mental retardation, developmental regression, nystagmus, microcephaly, irritability, hand stereotypies, increased serum lactate, constipation, abnormal movements, scoliosis, pneumonia, hearing impairment, epileptic encephalopathy, sleep problems, irritability.", "FRIAS SYNDROME": "Clinical features of the rare genetic disorder include: peculiar facies with downslanting palpebral fissures, epicanthic folds, hypertelorism, and ptosis; slower psychomotor development; low average intelligence; cup-shaped and posteriorly rotated ears; square hands with short stubby fingers, clinodactyly of the fifth fingers, and ulnar deviation of the index fingers; short toes with moderate hallux valgus; shortened middle phalanges of digits 2 to 5 of the hands and feet; retarded bone age; bilateral ptosis requiring surgical repair; mild exophthalmia; micrognathia; pedunculated postminimi; small, broad big toes; delayed bone age; short stature; small proximal syndactyly between fingers 2 and 3; bowed fifth metacarpals; ulnar deviation of the index fingers; variable expressivity; possible X-linked inheritance; diaphragmatic hernia; segmental hypoplasia of the corpus callosum; mild increase in ventricular size; altered eruption of dentition.", "ECTODERMAL DYSPLASIA 1, HYPOHIDROTIC, X-LINKED, Ectodermal dysplasia (select examples)": "Clinical features of this rare genetic disorder include characteristic facies in affected males, with frontal bossing, maxillary hypoplasia, 'saddle' nose, prominent lips, and linear wrinkles around the eyes. Teeth are often missing or misshapen, hair is fine, dry, brittle, and sparse, and skin is thin, glossy, smooth, and dry with hypohidrosis. Females have sparse, thin scalp hair and mosaic patchy distribution of body hair. Many females also have abnormal teeth and mild hypohidrosis. The disorder is highly penetrant and X-linked, with intermediate expression in heterozygous females. Other clinical findings include immunodeficiency, respiratory infections, and dental abnormalities.", "HENNEKAM LYMPHANGIECTASIA-LYMPHEDEMA SYNDROME 2, Hennekam lymphangiectasia-lymphedema syndrome": "Clinical features of the rare genetic disorder, Hennekam syndrome, include intestinal lymphangiectasia, severe lymphedema of the limbs, genitalia, and face, severe mental retardation, hypoproteinemia, hypogammaglobulinemia, lymphocytopenia, flat face, flat nasal bridge, hypertelorism, epicanthal folds, small mouth, tooth anomalies, ear defects, seizures, erysipelas, autosomal recessive inheritance, facial anomalies similar to Van Maldergem syndrome, syndactyly, camptodactyly, craniosynostosis, ectopic kidney, mild cognitive impairment, protein-losing gastroenteropathy, hearing loss, primary hypothyroidism, hypertrophic pyloric stenosis, poor overall growth, microcephaly, hepatosplenomegaly, polyhydramnios, hypogammaglobulinemia, lymphangiomatosis, cardiac anomalies, blood vessel anomalies, glaucoma, dental anomalies, renal anomalies, variable psychomotor development, convulsions, nonimmune hydrops fetalis, chylothorax, pulmonary lymphangiectasia, abnormalities of the middle ear, anomalous pulmonary venous drainage, interrupted inferior vena cava, polysplenia, crossed renal ectopia, median position of the liver, multiple cavernous hemangiomas, altered fluid dynamics, generalized lymphedema, hydrops, pleural effusions, ascites, diarrhea, low serum albumin, dysmorphic facies, and a history of in utero edema.", "CHROMOSOME 1q41-q42 DELETION SYNDROME": "Clinical features of the rare genetic disorder associated with heterozygous deletion of chromosome 1q41-q42 include significant developmental delay, distinct facial dysmorphism (frontal bossing, deep-set eyes, broad nasal tip, depressed nasal bridge, and anteverted nares), coarse facies in infancy, microcephaly, cleft palate, clubfeet, seizures, short stature, and in some cases, diaphragmatic hernia and lung hypoplasia. The disorder can also present with multiple congenital anomalies such as pulmonary hypoplasia, talipes equinovarus, undescended testes, and dysmorphic facial features. Holoprosencephaly, a brain abnormality, can also be observed in some cases.", "OROFACIODIGITAL SYNDROME VI, Orofaciodigital syndrome": "Clinical features of this rare genetic disorder, known as Orofaciodigital Syndrome (OFD), include abnormal oral frenula, alveolar and lingual clefting, asymmetry of the cranial vault, nasal fossae, and mandible, cleft lip/palate, aplasia of alar cartilages, digital malformations, familial tremor, mental retardation, polycystic kidneys, renal failure, agenesis of the corpus callosum, irregular mineralization of bones, central nervous system malformations, heart defects, and phenotypic overlap with other syndromes. OFD has been classified into multiple subtypes, with varying clinical and molecular heterogeneity. Some forms of OFD are associated with specific genetic mutations.", "CRANIOMETAPHYSEAL DYSPLASIA, AUTOSOMAL DOMINANT, Craniometaphyseal dysplasia": "Craniometaphyseal dysplasia is a rare genetic disorder characterized by dysplasia of the metaphyses, sclerosis of the base of the skull, and overgrowth of the craniofacial bones. It differs from Pyle disease in the involvement of craniofacial bones. Symptoms include widening of the bridge of the nose, leonine facies, facial palsy, mixed hearing loss, macrocephaly, hypertelorism, skull hyperostosis, paranasal bossing, teeth crowding, and metaphyseal flaring. The severity and progression of symptoms can vary.", "NOONAN SYNDROME-LIKE DISORDER WITH LOOSE ANAGEN HAIR 1, Noonan syndrome-like disorder with loose anagen hair": "Noonan syndrome-like disorder with loose anagen hair is characterized by facial features similar to Noonan syndrome, short stature, cognitive deficits, cardiac defects (especially mitral valve dysplasia and septal defects), ectodermal abnormalities (including easily pluckable, sparse, thin, slow-growing hair), and other features such as hypertelorism, ptosis, downslanting palpebral fissures, low-set posteriorly angulated ears, overfolded pinnae, relative macrocephaly, small posterior fossa resulting in Chiari I malformation, and hypernasal voice.", "PETERS-PLUS SYNDROME": "Clinical features of Peters anomaly and Peters-plus syndrome include corneal clouding, iridolenticulocorneal adhesions, short stature, brachymorphism, abnormal ears, cleft lip and palate, clinodactyly of the fifth finger, severe mental retardation, thin upper lip, hypoplastic columella, round face, hydrocephalus, and cranial atrophy. Other features include mesomelic brachymelia, macrocephaly, hypoplastic genitalia, anterior chamber cleavage anomalies, communicating hydrocephalus, polyhydramnios, depressed nasal bridge, micrognathia, tapering brachydactyly, and delayed development. Inheritance is autosomal recessive, and the disorder is associated with prenatal growth retardation and mental delay.", "FILIPPI SYNDROME": "Rare genetic disorder with craniodigital syndrome, mental retardation, delayed development, abnormal facies (brachycephaly, small nose, \"startled\" appearance, thick head hair, long eyelashes, thick eyebrows, short mandible), soft-tissue syndactyly between toes and fingers, unusual dermatoglyphic patterns, microcephaly, severe physical and mental retardation, broad-based nose, cutaneous syndactyly of toes and fingers, dysmorphic face, brachymesophalangy, pre- and postnatal short stature, low birth weight, cleft palate, speech involvement, skeletal anomalies, growth retardation, cryptorchidism, learning difficulties, polydactyly, high nasal bridge, peculiar metacarpophalangeal profile, cerebellar atrophy, axial hypotonia, limb hypertonia, typical facial dysmorphism, unusual teeth and hair, neurologic and ectodermal involvement, intrauterine growth retardation, microsomia, delayed psychomotor development, fine hair, synophrys, hypertelorism, bulbous nasal tip, anteverted ears, shallow philtrum, thin lips, generalized hirsutism, Chiari type I malformation, delayed bone age, variable expressivity, dominant inheritance, enlarged subarachnoid spaces and lateral ventricles, megacisterna magna.", "IMMUNODEFICIENCY 23": "Rare genetic disorder: Recurrent bacterial infections, neutrophil chemotactic defect, neutropenia, eosinophilia, high IgA levels, poor antibody response, absent cell-mediated immunity, chronic eczema, autoinflammatory arthritis, severe dermatitis, recurrent respiratory infections, low-average IQ, oral motor deficits, ataxia, sensory impairment, high-arched palate, narrow palpebral fissures, conductive hearing loss, cutaneous vasculitis, increased serum IgE, IgA, and IgG, atopic dermatitis, asthma, allergies, Epstein-Barr virus viremia, autoimmune diseases, neutropenia, leukopenia, decreased CD8-positive T cells, increased cytokines, glycosylation defect, failure to thrive, delayed psychomotor development, dysmorphic facial features, SCID phenotype, low B and T cells, normal NK cells, eczema, gastroesophageal reflux, Desbuquois dysplasia-like skeletal anomalies, short stature, brachydactyly, intellectual disability.", "TRICHORHINOPHALANGEAL SYNDROME, TYPE II": "Langer-Giedion syndrome (LGS) is characterized by dysmorphic facial features, sparse scalp hair, winged scapulae, redundant skin, and mental impairment. It may be inherited in an autosomal dominant manner. Complications include delayed speech development, hearing loss, hydrometrocolpos, hematometra, ureteral reflux, persistent cloaca, prune belly sequence, submucous cleft palate, limb abnormalities (bilateral tibial hemimelia, absence of ulna), and growth hormone deficiency. Cognitive impairment, seizures, scoliosis, and cervical spinal exostoses may occur in adulthood. Hair loss and gynecomastia are common in males, while serious eye, ear, and heart complications are rare.", "ARTHROGRYPOSIS, DISTAL, TYPE 5D": "Distal arthrogryposis (DA) is a rare genetic disorder characterized by joint contractures and limited mobility. Common features include flexion contractures of fingers 3 to 5, limited knee flexion, and talus valgus deformity of the feet. Lower limbs are more affected than upper limbs, with no major elbow or shoulder girdle contractures. Hip involvement, short neck, and lower extremity muscle atrophy are frequent findings. Scoliosis and pulmonary insufficiency may occur. Other features include hyperlaxity of distal joints, spared index finger, central tongue atrophy, ptosis, and muscle abnormalities. In some cases, additional features like cleft palate, hair upsweep, and ophthalmologic abnormalities may be present.", "CHROMOSOME 2q37 DELETION SYNDROME": "Clinical features of the rare genetic disorder include short stature, stocky build, mental retardation, brachymetaphalangia, eczema, dysmorphic facial features (such as midface hypoplasia, broad face and nose, brachycephaly, frontal bossing, downturned lower lip, and upslanted eyes), hyporeflexia, wide-based gait, sensorineural hearing loss, decreased sensitivity to pain, onychotillomania, hyperactivity, decreased attention span, sleep abnormalities, obesity, brachydactyly type E (BDE) with shortened metacarpals and metatarsals, hypotonia, hypermobility, pes planus, and various dysmorphic facial features. Some patients may also have subvalvular aortic stenosis, seizures, and congenital heart malformations. The disorder is associated with deletions or point mutations in the HDAC4 gene on chromosome 2q37. However, the presence of brachydactyly is variable and not always associated with cognitive defects.", "DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 2": "Clinical features of the rare genetic disorder include early-onset severe infantile spasms, profound global developmental arrest, hypsarrhythmia, severe mental retardation, hand-wringing and hand-mouthing stereotypies, breathing dysfunction with hyperventilation and breath-holding episodes, small hands and feet, wheelchair-dependence, mild mental retardation and autistic features, spastic quadriparesis, cortical blindness, marked kyphoscoliosis, delayed psychomotor development, lack of verbal communication skills, scoliosis, acquired microcephaly, hand apraxia, generalized hypotonia, frameshift deletions in CDKL5 gene, early-onset seizures, delayed psychomotor development, pseudoperiodicity and polyspike-wave discharges in EEG, three successive stages of the disorder (early epilepsy, epileptic encephalopathy, late multifocal and myoclonic epilepsy), delayed myelination and cerebellar atrophy in brain MRI, severely impaired gross motor, language, and hand function skills, dysmorphic features, hand stereotypies, gastrointestinal problems, spinal curvature, sleep problems, lack of developmental regression, mild facial dysmorphic features, psychomotor regression, somatic mosaic for a truncating mutation in CDKL5 gene, cerebral atrophy, severe mental retardation, and somatic mosaicism.", "HAO-FOUNTAIN SYNDROME": "Clinical features of the rare genetic disorder include developmental delay, intellectual disability, autism spectrum disorder, seizures, cryptorchidism or micropenis in males, hypotonia, aggressive behavior, poor or absent speech with speech apraxia, global developmental delay, impaired intellectual development, significant speech delay, delayed motor development, abnormal gait, behavioral abnormalities (autism, impulsivity, compulsivity, etc.), seizures, feeding difficulties, sleep disturbances, eye abnormalities, abnormal brain MRI findings (decreased white matter, enlarged ventricles, etc.), and dysmorphic facial features.", "DEVELOPMENTAL DELAY, HYPOTONIA, MUSCULOSKELETAL DEFECTS, AND BEHAVIORAL ABNORMALITIES": "Patients with DEHMBA, a rare neurodevelopmental disorder, exhibit global developmental delay, intellectual disability, behavioral and psychiatric problems, nonspecific facial features, musculoskeletal issues, and hypotonia. They lack the characteristic dysmorphic facial gestalt associated with FLHS and do not have short stature or delayed bone age. Speech and motor delay, as well as mildly impaired intellectual development, are common. Behavioral abnormalities include autism spectrum disorder, challenging behavior, anger, anxiety, ADHD, tics, Tourette syndrome, and psychosis. Skeletal anomalies include joint hypermobility, chronic musculoskeletal pain, scoliosis, and pectus defects. Dysmorphic facial features are variable and nonspecific. Some patients may have seizures, genitourinary abnormalities, or gastroesophageal reflux. Facial recognition algorithms cannot distinguish patients with DEHMBA from controls, indicating a lack of a unifying facial gestalt. The location of the mutation in the SRCAP gene does not significantly affect the phenotype.", "GENITOPATELLAR SYNDROME": "Clinical features of genitopatellar syndrome include absent patellae, genital anomalies (such as scrotal hypoplasia and cryptorchidism in males, and clitoral hypertrophy and prominent labia minora in females), renal anomalies (such as multicystic kidneys or hydronephrosis), dysmorphic features (such as coarse facies, prominent nose with a high nasal bridge, microcephaly, and micrognathia), flexion deformities of the knees and hips with clubfeet, and mental retardation. Other features may include agenesis of the corpus callosum, pulmonary hypoplasia, brachydactyly, and skeletal deformities. Some patients may also have congenital heart defects, anal anomalies, ectodermal dysplasia, and hearing loss. Severe cases may present with osteoporosis, kyphoscoliosis, and delayed puberty.", "OHDO SYNDROME, SBBYS VARIANT": "Clinical features of the rare genetic disorder include congenital heart defects, hypothyroidism, mental retardation, and facial dysmorphism such as blepharophimosis. Additional symptoms reported include macular degeneration, torticollis, talipes equinovarus, and patella dislocation. Brain imaging showed delayed myelination and disrupted white matter integrity. Patients also exhibited developmental delay, impaired intellectual development, and dysmorphic features such as bulbous nose and downslanting palpebral fissures. Familial transmission of the disorder was observed, suggesting underreporting of milder phenotypes.", "ARTHROGRYPOSIS, DISTAL, TYPE 2A": "Craniocarpotarsal dystrophy, also known as Freeman-Sheldon syndrome (FSS), is a rare genetic disorder characterized by skeletal malformations and distinct facial features. Skeletal malformations include camptodactyly with ulnar deviation, talipes equinovarus, and abnormal x-ray appearance of the skull. Facial characteristics include deep-sunken eyes with hypertelorism, increased philtrum length, small nose and nostrils, and a small mouth. FSS can be inherited in an autosomal dominant pattern and may be associated with other conditions such as scoliosis, glaucoma, and hearing loss. Treatment often involves orthodontic and surgical interventions.", "DIGEORGE SYNDROME": "Clinical features of DiGeorge syndrome include neonatal hypocalcemia, susceptibility to infection, hypoplasia or aplasia of the thymus gland, cardiac malformations (such as tetralogy of Fallot), micrognathia, low-set ears, telecanthus, short philtrum, small mouth, learning difficulties, and psychiatric disorders. Other less common features include hypothyroidism, cleft lip, and deafness. The syndrome is associated with a 22q11.2 deletion and can vary in severity and presentation among individuals. Neonatal seizures and hypocalcemia are significant predictors of more severe intellectual disability.", "FRONTOMETAPHYSEAL DYSPLASIA 1, Frontometaphyseal dysplasia": "Clinical features of the rare genetic disorder include:\n- Extraordinarily marked frontal hyperostosis with prominent supraciliary ridges\n- Underdeveloped mandible\n- Cryptorchidism\n- Subluxated radial heads\n- Metaphyseal dysplasia resembling Pyle disease\n- Progressive contracture of fingers and lysis and fusion of carpal bones\n- Progressive osteosclerosis\n- Broad thumbs\n- Lack of molding of long bone shafts\n- Scoliosis\n- Limited joint mobility\n- Dental abnormalities\n- Reduced dorsiflexion of wrists and extension of elbows\n- Flexion deformities of fingers and ulnar deviation of wrists\n- Obstructive uropathy and renal abnormalities in males\n- Congenital stridor and respiratory tract infections\n- Increased bone density, fused skull sutures, and flared metaphyses in neonates\n- Anterior bony spur from mandible\n- Complications such as esophageal atresia, tracheoesophageal fistula, and subglottic stenosis\n- Severe progressive scoliosis, hearing loss, and urogenital anomalies in some cases\n- Prominent supraorbital ridges, hypertelorism, micrognathia, pectus carinatum, kyphoscoliosis, and contractures in affected individuals\n- Thickened and sclerosed skull and facial bones\n- Erlenmeyer flask deformities in femurs\n- No extraskeletal manifestations in carrier mothers.", "3MC syndrome": "Clinical features of Michels syndrome (also known as 3MC syndrome) include blepharophimosis, blepharoptosis, epicanthus inversus, cleft lip/palate, skeletal abnormalities, craniosynostosis, telecanthus, hearing loss, and developmental defects of the eye. Other characteristics may include spina bifida occulta, cranial asymmetry, abnormality of the occipital bone, radioulnar synostosis, short fifth finger, low-set ears, large anterior fontanel, accessory nipples, tuberous angioma, supraumbilical depression, small hands with bilateral short fifth fingers, broad feet, and severe axial hypotonia. Growth hormone deficiency and secondary hypogonadism may also be present in some cases. The disorder is believed to be a single recessive spectrum encompassing Michels, Malpuech, Carnevale, and OSA syndromes.", "GLYCINE ENCEPHALOPATHY WITH NORMAL SERUM GLYCINE": "Clinical features of the rare genetic disorder, glycine encephalopathy, include impaired respiratory function at birth, hyperekplexia, axial hypotonia, weak cry, difficulty swallowing, failure to thrive, microcephaly, dysmorphic features, global developmental delay, hyperreflexia, joint laxity, and clubfeet. Skeletal anomalies such as arthrogryposis multiplex congenita, including clubfeet and clenched fists, are also observed. Other features include prenatal ultrasound abnormalities, severe hypotonia at birth progressing to hypertonia, and dysmorphic features such as trigonocephaly and retrognathia. Delayed psychomotor development, recurrent respiratory failure, and variable brain imaging abnormalities are also seen. Increased glycine levels in CSF and urine, but normal serum glycine, are observed. One patient developed hypertension and increased urinary catecholamines.", "EHLERS-DANLOS SYNDROME, DERMATOSPARAXIS TYPE": "Clinical features of the rare genetic disorder, dermatosparaxis type of Ehlers-Danlos syndrome (EDS), include severe joint hyperextensibility, stretchability, and bruisability of the skin. Other characteristics include short stature, epicanthal folds, depressed nasal bridge, micrognathia, blue sclerae, umbilical hernia, and delayed fontanel closure. Skin fragility is severe, with easy bruising, tearing, and extreme fragility. Collagen abnormalities are observed in skin samples, and there is impaired enzymatic conversion of procollagen to collagen. Dental anomalies, growth retardation, and joint laxity may also be present.", "EHLERS-DANLOS SYNDROME, MUSCULOCONTRACTURAL TYPE, 1": "Clinical features of this rare genetic disorder include muscle weakness at birth, clubfeet, fragile skin, delayed motor development, normal intellectual development, scoliosis, muscular hypotonia, hyperelastic skin, hyperalgesia to pressure, hyperflexibility of joints, high narrow palate, microcornea, mitral valve prolapse, cutaneous and subcutaneous hematomas, prolonged bleeding time, retinal detachments, dysmorphic facies, arachnodactyly, distal arthrogryposis, psychomotor developmental delay, ocular anterior chamber abnormality, and facial dysmorphism. Other features include broad bossed forehead, late-closing fontanel, telecanthus, downslanting palpebral fissures, posteriorly rotated ears, downturned angle of mouth, adducted thumbs, talipes equinovarus, ventricular enlargement, atrial septal defect, coarctation of the aorta, horseshoe kidney, thick eyebrows, blue sclerae, high-arched palate, low-set and slanted ears, cylindrical fingers, joint contractures, hearing impairment, urinary tract infections, constipation, kyphoscoliosis, skin fragility, subcutaneous hematomas, cardiac abnormalities, gastrointestinal complications, ophthalmologic complications, and connective tissue abnormalities.", "PITT-HOPKINS-LIKE SYNDROME 1": "Text 1 (Strauss et al., 2006): Cortical dysplasia-focal epilepsy syndrome (CDFE syndrome) in Amish children. Mild motor delay, normal growth, large heads, absent deep-tendon reflexes. Severe seizures starting at 2-7 years, leading to learning regression, social behavior abnormalities, mental retardation, hyperactivity, inattention, aggression. Focal brain malformations seen in some patients. Poor long-term outcome.\n\nText 2 (Orrico et al., 2001): Pitt-Hopkins syndrome (PTHS) in siblings. Severe mental retardation, coarse facial features, short stature, seizures, hypertrichosis, short great toes, overbreathing. Differences from typical PTHS patients: large noses, lack of curving upper lips, unilateral ptosis, normal motor development, different breathing abnormalities.\n\nText 3 (Smogavec et al., 2016): Intellectual disability with speech impairment, behavioral abnormalities, and early-onset seizures in 8 patients from unrelated families. Poor or absent speech, delayed walking, variable seizure types, EEG abnormalities. Some patients had temporal cortical dysplasia or vermian atrophy on brain imaging. Other neurologic abnormalities included hyporeflexia, hypotonia, ataxia, spasticity. Behavioral anomalies included stereotypic hand movements, aggressivity, autoaggressivity, reduced eye contact. No significant facial dysmorphism.\n\nText 4 (Zweier et al., 2009): Pitt-Hopkins syndrome (PTHS) in siblings and another patient. Short stature, lack of speech development, thick lips, wide mouth. Seizure onset around 2 years. One patient had cerebellar hypoplasia. No autistic features mentioned.\n\nNote: Token count exceeds 30.", "COFFIN-SIRIS SYNDROME 9, Coffin-Siris syndrome": "Coffin-Siris syndrome (CSS) is a rare genetic disorder characterized by dysmorphic facial features, microcephaly, growth deficiency, hypoplastic fifth toenails, and mild intellectual disability. Other common features include hypertrichosis, arched eyebrows, low-set and posteriorly rotated ears, and full cheeks. Patients may also exhibit speech impairment, developmental delay, and skeletal abnormalities. Some individuals with CSS may have additional features such as ocular motor apraxia, abnormal eye morphology, or hypogonadotropic hypogonadism. It is important to note that not all individuals with CSS exhibit the complete spectrum of the phenotype, and there is ongoing debate about the classification of CSS as a single entity.", "MEIER-GORLIN SYNDROME 2, Meier-Gorlin syndrome": "Clinical features of the rare genetic disorder include: intrauterine growth retardation, microcephaly, dolichocephaly, micrognathia, flat philtrum, hypoplasia of nasal alae, microtia, small external auditory meatuses, prominent clitoris, camptodactyly of fingers, hyperextensible joints, high-pitched voices, short stature, absent or hypoplastic patellae, feeding difficulties, tracheomalacia, clubfoot, breast hypoplasia, delayed bone age, and various craniofacial anomalies.", "NOONAN SYNDROME 6, Noonan syndrome": "Clinical features of Noonan syndrome include hypertelorism, low-set ears, short stature, webbed neck, curly hair, thorax deformities, hypotonia, and cryptorchidism in males. Other features may include speech delay, mental retardation, congenital heart defects, macrocephaly, myopia, and hyperkeratosis. The syndrome is genetically heterogeneous and can be caused by mutations in genes such as PTPN11, RIT1, SOS1, RAF1, BRAF, MAP2K1, MAP2K2, and SHOC2. Facial analysis technology can aid in diagnosis, but it is not a substitute for clinical evaluation. Motor performance may be impaired in individuals with Noonan syndrome, with decreased muscle strength and endurance.", "NEURODEVELOPMENTAL DISORDER WITH SPASTIC DIPLEGIA AND VISUAL DEFECTS": "Rare genetic disorder: CTNNB1 mutation\n- Severe intellectual disability, absent or limited speech\n- Microcephaly, short stature, spasticity impairing walking\n- Behavioral problems: aggression, automutilation, fecal smearing\n- Facial dysmorphism: low columella, long philtrum, high and narrow palate, small posteriorly rotated ears\n- Other common features: childhood hypotonia, autistic features, progressive spastic diplegia, hypoplasia of the corpus callosum\n- Additional features: delayed psychomotor development, peripheral spasticity, visual defects, mild dysmorphic facial features", "Cole-Carpenter syndrome": "Rare genetic disorder resembling osteogenesis imperfecta (OI) with additional features of ocular proptosis, craniosynostosis, hydrocephalus, and distinctive facial characteristics. Recurrent diaphyseal fractures occur after the first birthday. Intellectual development is unaffected. Other symptoms include failure to thrive, macrocephaly, micrognathia, high-arched palate, low-set ears, small limbs, and bowing of lower limbs. No obvious fractures, normal serum calcium, phosphorus, and alkaline phosphatase levels. CT scans show ventriculoperitoneal shunt and sutural diastasis. Connective tissue disorder signs include osteopenia, pathologic fractures, discolored teeth, blue sclerae, and easy bruising. Severe progressive type of OI with multisutural craniosynostosis, growth failure, and craniofacial abnormalities. Wheelchair-bound with short stature, severe scoliosis, limb deformities, and low bone mineral density in adulthood. Normal serum levels of calcium, phosphorus, creatinine, alkaline phosphatase, and parathyroid hormone.", "SILVER-RUSSELL SYNDROME 5, Silver-Russell syndrome": "Silver-Russell syndrome (SRS) is characterized by low birth weight, short stature, triangular face, broad forehead, small chin, thin mouth, body asymmetry, hepatocellular carcinoma, clinodactyly, growth deficiency, camptodactyly, genital abnormalities, feeding problems, sweating, pallor, special education needs, uniparental disomy of chromosome 7, gastrointestinal symptoms, ophthalmologic abnormalities, dysmorphisms, macrocephaly, low-set and posteriorly rotated ears, glucose intolerance, hypertension, hypercholesterolemia, impaired quality of life, educational achievement, difficulty in diagnosing adults, IUGR, macrocephaly, hypertelorism, micrognathia, brachydactyly, syndactyly, reduced musculature, cafe au lait spot, clitoral hypertrophy, delayed bone age, metaphyseal irregularity, reactive airway disease, delays in motor development, learning disability, ADHD, OCD, neonatal teeth, hydrocephalus, bicuspid aortic valve, hypothyroidism, rheumatoid arthritis, Crohn disease, and normal psychomotor development.", "DDX23": "The rare genetic disorder is characterized by a mutation in the PRP28 (DDX23) gene. The encoded protein is a 100-kD polypeptide with an N-terminal RS domain and a C-terminal domain containing conserved motifs of RNA-stimulated ATPases and RNA helicases. PRP28 is involved in mammalian pre-mRNA splicing and shares 37% sequence identity with the S. cerevisiae Prp28 protein.", "CK SYNDROME": "X-linked recessive mental retardation syndrome with seizures, delayed psychomotor development, hyperactivity, aggression, and irritability. Other features include hypotonia, hyperextensible joints, thin body habitus, microcephaly, almond-shaped eyes, high nasal bridge, high-arched palate, crowded teeth, and malar hypoplasia. Brain imaging showed polymicrogyria and/or pachygyria. Carrier females unaffected. Normal cholesterol levels in affected individuals and carriers.", "LEOPARD syndrome": "Clinical features of the rare genetic disorder, LEOPARD syndrome, include generalized lentigines, cardiac changes (such as myocardial infarction and pulmonary stenosis), stunted growth, abnormalities in reproductive organs (such as absent or hypoplastic ovaries, hypospadias, and undescended testes), behavioral immaturity, electrocardiographic changes, murmurs, left-sided obstructive cardiomyopathy, mental retardation (uncommon), deafness (uncommon), infantilism (uncommon), thoracic deformities leading to pulmonary hypertension, ocular hypertelorism, hair loss, and multiple granular cell tumors.", "MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 2": "Clinical features of the rare genetic disorder include: \n- Neonatal onset with symptoms such as psychomotor retardation, microcephaly, hypotonia, and growth retardation\n- Hypertrophic cardiomyopathy, dysmorphism, hypospadias, lactic acidosis, and increased urinary 3-methylglutaconic aciduria\n- Oligohydramnios, early delivery, intrauterine growth retardation, and neonatal hypotonia\n- Dysmorphic facial features, respiratory insufficiency, and multiorgan failure in severe cases\n- Gastrointestinal abnormalities, cataracts, and skeletal muscle complex V deficiency\n- Persistent pulmonary arterial hypertension, delayed psychomotor development, and poor overall growth\n- Seizure disorder, facial dysmorphism, cryptorchidism, leukoencephalopathy, and cerebellar atrophy\n- Mild cardiac hypertrophy, mega cisterna, buphthalmos, and hearing impairment\n- Acute episodes of vomiting and encephalopathy, hyperammonemia, and elevated plasma amino acids\n- Developmental delay, atrial septal defect, left ventricular noncompaction, and multivalvular dysplasia\n- Chronic heart failure and developmental delay at later stages.", "SHORT STATURE, MICROCEPHALY, AND ENDOCRINE DYSFUNCTION": "Text 1: 14-year-old girl with short stature, microcephaly, developmental delay, motor difficulties, deep-set eyes, beaked nose, hearing loss, hand weakness, tremors, and thin corpus callosum.\n\nText 2: 23-year-old patient with short stature, microcephaly, developmental delay, neuronal degeneration, hyperopia, diabetes mellitus, hypothyroidism, hearing loss, and low-grade thalamic glioma.\n\nText 3: 4-year-old girl with severe short stature, microcephaly, triangular face, short philtrum, and speech delay.\n\nText 4: 6 patients with biallelic mutations in the XRCC4 gene, resulting in significant reductions in head and body size, fine sparse hair, small chin, broad nasal tip, and some developmental delay.\n\nText 5: 50-year-old twin brothers with short stature, dilated cardiomyopathy, cognitive impairment, nystagmus, dysarthria, ataxia, and axonal sensory neuropathy.\n\nText 6: Brother and sister with severe short stature, microcephaly, gonadal failure, metabolic syndrome, insulin resistance, cataracts, and gastrointestinal stromal tumor.\n\nText 7: 3 Turkish brothers with short stature, microcephaly, psychomotor delay, dysmorphic facial features, thrombocytopenia, undescended testes, and inguinal hernia.\n\nText 8: 14-year-old Swiss girl with short stature, microcephaly, mild developmental delay, dysmorphic facial features, and truncal obesity.", "CARDIOFACIOCUTANEOUS SYNDROME 1, NOONAN SYNDROME 7, Cardiofaciocutaneous syndrome, Noonan syndrome": "Clinical features of the rare genetic disorder, Noonan syndrome-7, include poor neonatal growth, feeding difficulties, short stature, cognitive defects, skeletal anomalies, and hypotonia. Dysmorphic facial features include dolichocephaly, prominent forehead, hypertelorism, and low-set ears with thickened helices. Congenital cardiac defects, pulmonary stenosis, and atrial septal defect are also common. Other features may include hyperpigmented cutaneous lesions, webbing of the neck, coarctation of the aorta, cryptorchidism, pterygium colli, myocardiopathy, and pulmonary valvular dysplasia. The disorder shows similarities to Turner syndrome and Ullrich-Turner syndrome.", "CORNELIA DE LANGE SYNDROME 2, WIEDEMANN-STEINER SYNDROME, Cornelia de Lange syndrome": "Thin vermilion border Bilateral single transverse palmar creases Global developmental delay Intrauterine growth retardation Anteverted nares Hypoplastic labia majora Curly eyelashes Posteriorly rotated ears Thick eyebrow Micromelia Cutis marmorata Micrognathia Hypoplastic nipples Downturned corners of mouth Small hand Brachycephaly Clinodactyly of the 5th finger Oligodactyly Depressed nasal bridge Generalized hirsutism Proximal placement of thumb Short stature Downturned corners of mouth Feeding difficulties in infancy Truncal obesity Conductive hearing impairment Asymmetric growth Long philtrum Toe syndactyly Micromelia Global developmental delay Short nose Hearing impairment Cryptorchidism Thin vermilion border Myopia Low posterior hairline Abnormally low-pitched voice Micrognathia Abnormality of speech or vocalization Short stature Widely spaced teeth Radioulnar synostosis Wide nasal bridge Low-set ears Long eyelashes Limited elbow extension Wide nasal bridge Intestinal malrotation Severe postnatal growth retardation Intellectual disability, severe Proximal placement of thumb Short 1st metacarpal Attention deficit hyperactivity disorder Microcephaly Failure to thrive Hypoplasia of penis Toe syndactyly Gastroesophageal reflux Thick eyebrow Premature birth Abnormal aggressive, impulsive or violent behavior Highly arched eyebrow obsolete Abnormality of the ulna Prenatal movement abnormality Atrial septal defect Abnormality of cardiovascular system morphology Synophrys Synophrys Intellectual disability Short foot Microcephaly Talipes Intellectual disability, severe Ptosis Blepharitis High palate Low-set ears Strabismus Sensorineural hearing impairment Seizure Increased nuchal translucency Thickened helices", "MICROCEPHALY, GROWTH DEFICIENCY, SEIZURES, AND BRAIN MALFORMATIONS": "Patients (14DG1157 and 14DG1160) with a rare genetic disorder had microcephaly, poor growth, and developmental delays. They had intrauterine growth retardation, short stature, and low weight. Dysmorphic features included a high forehead, prominent eyes, depressed nasal bridge, short philtrum, tented upper lip, and bulged alveolar ridge. Neurological evaluation showed hypertonia, spasticity, optic atrophy, and seizures. One patient had contractures of the elbows and hands. Brain imaging showed partial agenesis of the corpus callosum and abnormal gyral pattern. Radiographs showed unossified pubic bones and proportionately short long bones. The patients had no purposeful eye contact or speech and made no developmental progress.", "TONNE-KALSCHEUER SYNDROME": "Clinical features of the rare genetic disorder described in the texts include: \n- Mental retardation, delayed psychomotor development, and mild to moderate intellectual disability with poor speech\n- Autistic features and behavioral abnormalities\n- Dysmorphic facial features such as broad forehead, broad nasal bridge, hypertelorism, and micrognathia\n- Stiff gait, feeding difficulties, and growth retardation with microcephaly\n- Neurologic abnormalities including spasticity, tremor, and drooling\n- Congenital malformations such as congenital diaphragmatic hernia and cardiac defects\n- Genital anomalies in males including small penis, cryptorchidism, and hypospadias\n- Distal skeletal anomalies including short broad thumbs and pes planus\n- Carrier females may have physical features such as short stature and broad thumbs, and may also have premature ovarian insufficiency.", "Trichorhinophalangeal syndrome": "Clinical features of the rare genetic disorder described in the texts include thin and slowly growing hair, pear-shaped nose with high philtrum, brachyphalangy with finger deformation and wedge-shaped epiphyses. Other characteristics include supernumerary incisors, pseudo-pseudohypoparathyroidism, low-set posteriorly rotated ears, prominent malar eminence and orbital ridge, bulbous nose, hypoplastic nasi alae nasi, hypotrichosis, long philtrum, brachydactyly, wide halluces, flat arches, vertebral spondylosis, scoliosis, spondylolisthesis, shortening of phalanges, osteophyte formation, osteopenia, secondary arthritic changes, and cone-shaped epiphyses. Clinical variability is observed, with additional symptoms such as spastic paraplegia, dysarthria, low-normal intellectual capacity, and abnormal metaphyseal-phalangeal pattern profile. The disorder is caused by mutations in the SACS and TRPS1 genes, resulting in autosomal recessive spastic ataxia-6 and type I trichorhinophalangeal syndrome, respectively.", "COFFIN-SIRIS SYNDROME 3, Coffin-Siris syndrome": "Clinical features of the rare genetic disorder include:\n- Mental retardation\n- Absent or hypoplastic nails and terminal phalanx of the fifth finger\n- Hypertrichosis (excessive hair growth)\n- Dysmorphic facial features (low anterior hairline, thick arched eyebrows, broad nose with a broad tip and columella below alae nasi, short philtrum, thick drooping lower lip, simple posteriorly rotated ears)\n- Rough skin with hyperkeratotic plaques\n- Broad feet and fingertips\n- Thick and short corpus callosum on brain MRI\n- Mild short stature\n- Myopia and strabismus\n- Coarse facies\n- Behavioral abnormalities (severe obsessive-compulsive disorder, withdrawal, stubborn and obstinate behavior, autistic features)\n- Limited language and hoarse or high-pitched voice\n- Ventricular septal defect, patent ductus arteriosus, mild coarctation of the aorta, and hip dislocation in one patient\n- Muscular hypotonia\n- Abnormal head shape, low-set and abnormally shaped ears, downslanting palpebral fissures, bulbous nasal tip, thin upper lip, minor teeth anomalies, and brachydactyly or single palmar creases in some patients\n- Developmental delay\n- Hirsutism and coarse facial appearance with flat nasal bridge, broad nose, and thick lips\n- Frequent infections\n- Severe speech delay\n- Agenesis or partial agenesis of the corpus callosum\n- SMARCB1 mutations in some patients\n- Sparse scalp hair, long eyelashes, abnormal delayed dentition, nonfunctioning or absent tear duct, and short stature in some patients\n- Spinal anomalies, feeding problems, and delayed bone age in some patients\n- Poor overall growth, microcephaly, congenital heart defects, hearing impairment, small cerebellum, and abnormal corpus callosum in patients with CSS3", "NABLUS MASK-LIKE FACIAL SYNDROME": "Rare genetic disorder: Nablus mask-like facial syndrome (NMLFS)\n- Striking facial appearance: upswept frontal hairline, tight glistening facial skin, high-arched and sparse eyebrows, absent/scant eyelashes, hypertelorism, blepharophimosis, bulbous nasal tip, prominent smooth philtrum, maxillary hypoplasia with bilateral longitudinal cheek dimples, everted lower lip, small chin, abnormal ear configuration\n- Other characteristics: camptodactyly, contractures, unusual dentition, cryptorchidism, developmental delay\n- Happy demeanor observed in affected individuals\n- Parental consanguinity likely in some cases\n- Normal psychomotor development in some individuals\n- Abnormal head circumference, ear length, and unfolded helix observed in some cases\n- 'Sandal gap' between first and second toes in some cases\n- Fourth case reported with broad neck, contractures of large joints, and small testicular scrotum", "PLXND1": "Rare genetic disorder: Mutation in PLXND1 gene\nClinical features:\n- Congenital heart defects: Truncus arteriosus, tetralogy of Fallot, transposition of the great arteries, double-outlet right ventricle\n- Other cardiovascular defects: Common arterial trunk, interrupted aortic arch, bicuspid/quadricuspid aortic valve, right aortic arch\n- Additional anomalies: Neuroblastoma, Hirschsprung disease, developmental delay, dysmorphic features, intrauterine growth retardation, cystic hygroma\n- Ethnicities affected: Iranian Jewish, North African, African American, Caucasian, Hispanic, Mandinka, Chinese, Irish\n- Associated malformations: Persistent left superior vena cava, interrupted aortic arch, hypoplastic ventricle, dilated ventricle, single ventricle, single outlet artery, mitral atresia, aberrant right subclavian artery", "REV3L": "The yeast gene encodes DNA polymerase zeta, responsible for DNA damage-induced and spontaneous mutagenesis. The human gene encodes a larger protein with 3,130 residues, compared to the yeast protein with 1,504 amino acids. The two proteins share 29% identity in the amino-terminal region, 39% identity in the carboxy-terminal region, and 29% identity in a middle region of 55 residues.", "NOONAN SYNDROME 9, Noonan syndrome": "Noonan syndrome is characterized by various clinical features including short stature, webbed neck, dysmorphic facial features (such as downslanting palpebral fissures, hypertelorism, and ptosis), cardiac defects (such as septal defects, coarctation of the aorta, and pulmonary valve stenosis), ectodermal abnormalities (such as curly hair, sparse eyebrows, hyperkeratosis pilaris, and ulerythema ophryogenes), developmental delay and/or learning disabilities, and coagulation defects. Tumors are not typically associated with Noonan syndrome.", "A2ML1": "This text describes the clinical features of a rare genetic disorder related to otitis media. It suggests a genetic contribution to susceptibility, with higher frequency in American Indians and Australian aborigines. Family studies show familial aggregation for otitis media, mastoid size, and cholesteatoma. A study on Apache Indians estimated the heritability of otitis media, finding a strong genetic component. Primary care clinicians should closely observe siblings of otitis media-prone children.", "MENTAL RETARDATION, AUTOSOMAL RECESSIVE 7": "Rare genetic disorder: \n- Nonsyndromic moderately to severely impaired intellectual development\n- Consanguineous Iranian kindred, French parents, and Omani family affected\n- Variable developmental delay with intellectual disability (IQ range 40-50) and language delay\n- Autism spectrum disorder in one patient\n- Poor overall growth with short stature and small head circumference\n- Mild dysmorphic features including hypertelorism, long face, deep-set eyes, thin philtrum, and pointed chin\n- Distal anomalies of fingers and toes (camptodactyly and syndactyly)\n- Normal brain imaging in one patient\n- Difficulties in school, poor fine motor skills, limited speech, and difficulty chewing and swallowing", "HEMIFACIAL MICROSOMIA; HFM": "Hemifacial microsomia is characterized by unilateral deformity of the external ear and small ipsilateral half of the face. Other features include epibulbar dermoid, vertebral anomalies, coloboma of the upper eyelid, and ear deformities ranging from preauricular tags to atresia of the external auditory canal. The disorder is part of the oculoauriculovertebral dysplasia spectrum and is associated with Goldenhar syndrome. Phenotypic variability is observed, with some individuals having mild involvement and others having severe manifestations such as microtia, preauricular skin tags, macrostomia, and hypoplasia of the ramus and condyle. Other associated anomalies include cardiac, ocular, and vertebral abnormalities. The condition may be more common in infants of diabetic mothers and may be associated with genetic factors such as del22q11 and SF3B2 gene mutations.", "INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC, SNYDER-ROBINSON TYPE": "Clinical features of Snyder-Robinson syndrome include: X-linked mental retardation, hypotonia, unsteady gait, asthenic body build, diminished muscle bulk, osteoporosis, kyphoscoliosis, long thin face, facial asymmetry, nasal voice, high narrow or cleft palate, long thin fingers and toes, seizures, abnormal EEG, short stature, facial dysmorphism, hypertelorism, exophthalmia, short philtrum, thickened lower lip, high-arched palate, mandibular prognathism, prominent antihelices and hypoplastic lobules, high myopia, pectus carinatum, cryptorchidism, camptodactyly, muscular hypotonia, dysmorphic facial features, myoclonic seizures, decreased cerebellar volume, decreased hippocampal and red nucleus volumes, mental retardation, childhood fractures, decreased bone density, thin body habitus, pectus excavatum, widely-spaced nipples, brachycephaly, asymmetric facies, slanted upper palpebral fissures, sparse eyebrows, synophrys, right palpebral ptosis, high nasal bridge, bulbous nasal tip, anteverted nares, smooth philtrum, prominent lower lip, high palate, overcrowded teeth, asymmetric ears, short webbed neck, patchy skin hyperpigmentation, delayed psychomotor development, delayed language, thin build, low-set ears, small mouth, good social interaction, cognitive impairment, nasal speech, ectopic right kidney, early onset of epilepsy, and myoclonus.", "JAWAD SYNDROME": "Clinical features of the rare genetic disorder include congenital microcephaly, moderately severe mental retardation, and digital anomalies such as hallux valgus, syndactyly, short fifth fingers, and lack of distal interphalangeal crease. Other characteristics may include a sharply sloping forehead, anonychia congenita, polydactyly, synpolydactyly, and white spots on the skin. The disorder is distinct from Filippi syndrome due to the absence of cryptorchidism, striking physical retardation, and striking facial changes. A similar syndromic form of congenital microcephaly has been reported in a consanguineous Pakistani family.", "KABUKI SYNDROME 1, CHARGE SYNDROME, Kabuki syndrome": "Clinical features of the rare genetic disorder, CHARGE syndrome, include choanal atresia, coloboma of the eye, heart anomalies, mental and somatic development retardation, microphallus, ear abnormalities and/or deafness. Facial palsy, cleft palate, and dysphagia are commonly associated. Other features may include low-set and dysplastic ears, retrogenia, antimongoloid slant of palpebral fissures, and anteverted nares. Additional malformations such as orofacial clefts and esophageal atresia may also be present. Infants with bilateral choanal atresia plus cardiac defects and those with choanal atresia plus renal malformations have a high mortality rate. The syndrome is a recognizable pattern of malformations and a true syndrome rather than an association. Other associated features include feeding difficulties, genital hypoplasia, abnormal ears, cleft lip and palate, pectus carinatum, and growth retardation. The syndrome is characterized by a wide range of clinical manifestations and variable expressivity.", "NOONAN SYNDROME-LIKE DISORDER WITH LOOSE ANAGEN HAIR 1, Moyamoya disease, Noonan syndrome-like disorder with loose anagen hair": "Juvenile moyamoya disease: Transient motor disturbances due to narrowing/occlusion of circle of Willis. Adult moyamoya disease: Intracranial hemorrhage due to collapse of collateral circulation. 10% cases familial, 76% sibs, 24% parent-offspring. Asymptomatic family members identified. Antiplatelet-aggregating and calcium-antagonist drugs effective. Childhood onset, maternal grandmother also affected. Moyamoya disease in 3 sibs. Recurrent cerebrovascular events in sickle cell patients with moyamoya collaterals. Multigenic origin of phenotype in monogenic disorder. Noonan syndrome-like disorder: Facial features similar to Noonan syndrome, short stature, cognitive deficits, cardiac defects, hair anomaly.", "CRANIOSYNOSTOSIS 1, Craniosynostosis": "Rare genetic disorder: Multiple cases in South African families, scaphocephaly, craniostenosis, dolichocephaly, oxycephaly, coronal craniosynostosis. Male-to-male transmission, affected children of unaffected mothers, deletion of short arm of G chromosome, normal intelligence. Familial involvement, bilateral coronal involvement, multiple or total synostosis. Holocalvarial craniosynostosis with minimal dysmorphic features, normal psychomotor development. Autosomal dominant transmission, self-limited disorder.", "ROBINOW-SORAUF SYNDROME": "Distinct acrocephalosyndactyly syndrome described as Robinow-Sorauf syndrome, characterized by Saethre-Chotzen-like facies and broad big toes due to duplication of distal phalanx. Different from Pfeiffer syndrome, which resembles Crouzon syndrome and has abnormal proximal phalanx of big toe. Male-to-male transmission observed. Reardon and Winter suggest merging Robinow-Sorauf syndrome with Saethre-Chotzen syndrome.", "SWEENEY-COX SYNDROME": "Severe facial dysmorphism with marked hypertelorism, upper eyelid colobomas, deficient bony orbits, and hypoplastic alae nasi. Other features include high-arched palate, micrognathia, dysplastic cupped ears, and flattening of the occiput. Additional findings include small frontal bones, hypoplastic midface, broad neck, narrow shoulders, and syndactyly. Other symptoms include talipes equinovarus, undescended testes, imperforate anus, hirsutism, learning disability, and hearing loss. A girl with the same disorder had a brachycephalic skull, open metopic suture, hypertelorism, colobomas, cleft palate, and syndactyly. She also had abnormal hair patches, absent spleen, and developmental delay. The disorder is named 'Sweeney-Cox syndrome' after the clinicians who recognized its common features.", "DUANE-RADIAL RAY SYNDROME": "Clinical features of the rare genetic disorder include:\n- Radial defects (ranging from hypoplasia of thenar musculature to absence of thumb and first metacarpal)\n- Duane anomaly (limited eye movement)\n- Atrial septal defect (in some cases)\n- Kidney anomalies (malrotation, horseshoe anomaly, crossed renal ectopia)\n- Limb anomalies (pectoral and upper limb hypoplasia, club hand deformity)\n- Ocular abnormalities (coloboma, ptosis, optic nerve abnormalities)\n- Hearing loss (sensorineural, bilateral)\n- Dermatoglyphic abnormalities\n- Anal stenosis (in some cases)\n- Microphthalmia, microcornea, cataract\n- Urologic abnormalities (vesicoureteral reflux, bladder diverticula)\n- Epicanthic folds, hypertelorism\n- Flat feet and large sandal gaps", "ANGELMAN SYNDROME": "Clinical features of Angelman syndrome include abnormal cranial shape, severe motor and intellectual retardation, ataxia, hypotonia, epilepsy, absence of speech, unusual facies with large mandible and open-mouthed expression, excessive laughter, protruding tongue, abnormal choroidal pigmentation, characteristic EEG discharges, optic atrophy, jerky movements, poor balance, major convulsions, flapping of arms, high amplitude bilateral spike-and-wave EEG activity, unilateral cerebellar atrophy, deficiency of choroidal pigment, light blue irides, global developmental delay, tongue thrusting, microcephaly, seizures, hypopigmentation, hyperreflexia, hyperkinesis, absent speech, hypopigmentation, large mouth, ataxic gait, kyphosis, absence of speech, brachycephaly, hearing loss, enlarged foramen magnum, happy affect with excessive laughter, generalized and partial seizures, refractive errors, strabismus, ocular hypopigmentation, active seizures, sleep dysfunction, constipation, obesity, scoliosis, self-injurious behavior, and impaired communication.", "PONTOCEREBELLAR HYPOPLASIA, TYPE 1B": "Clinical features of the rare genetic disorder include: severe hypotonia, respiratory insufficiency, poor feeding, joint contractures, foot deformities, visual inattention, muscle weakness, dysmorphic facies, psychomotor delay, nystagmus, microcephaly, pontocerebellar hypoplasia, cerebellar atrophy, spinal cord anterior horn cell degeneration, neurogenic atrophy, and global developmental delay.", "PBX1": "Clinical features of the rare genetic disorder include:\n- Kidney defects such as renal hypoplasia, dysplasia, ectopia, and horseshoe kidney\n- Urinary tract abnormalities including bifid ureter, small urethral valve, renal pelvis dilatation, and vesicoureteral reflux\n- Chronic kidney disease and end-stage renal disease requiring dialysis\n- Cryptorchidism in males\n- Global developmental delay, speech delay, motor delay, hearing impairment, hypotonia, and autism spectrum disorder\n- Dysmorphic facial features such as broad nasal bridge, anteverted nares, hypertelorism, strabismus, prominent philtrum, and thin upper lip\n- Abnormal outer ears that are low-set, hypoplastic, abnormally hemmed, and anteverted or crumpled\n- Other organ malformations including heart defects, neurologic abnormalities, and anal malposition\n- Deletions of several contiguous genes contributing to extrarenal symptoms\n- Truncating point mutations in the PBX1 gene leading to renal hypoplasia, deafness, scoliosis, developmental delay, growth retardation, and dysmorphic facial features\n- Pleiotropic developmental disorder associated with de novo heterozygous point mutations in the PBX1 gene, resulting in delayed development, poor growth, short stature, hypotonia, craniofacial anomalies, renal anomalies, and genital abnormalities.", "TRIP12": "Clinical features of the rare genetic disorder include impaired intellectual development, macrocephaly, square forehead, prominent supraorbital ridges, broad nasal tip, prominent lower lip, large ears, obesity, macroorchidism, tall stature, large hands, a gap between central incisors, normal eye spacing, behavior problems, dysmorphic facial features (such as hypertelorism, epicanthal folds, short nose, depressed nasal bridge, low columella, long philtrum, wide mouth, high-arched palate, and large ear lobes), and mild abnormalities of the hands or feet (such as clinodactyly and sandal gap).", "FOXA2": "Genes encode polypeptides of different lengths. Hnf3a and Hnf3b expressed in endodermal tissues like stomach, intestines, liver, and lung. Hnf3g expressed in more tissues including ovary, testis, heart, and adipose tissue, but not in lung.", "NOONAN SYNDROME 4, Noonan syndrome": "Noonan syndrome is characterized by various clinical features including webbed neck, coarctation of the aorta, cryptorchidism, pterygium colli, deformed sternum, pulmonary stenosis, patent ductus arteriosus, elevated alkaline phosphatase levels, myocardiopathy, seizures, anomalous upper lateral incisors, lymphedema, posterior cervical hygroma, cutaneous lymphangioma, craniofacial anomalies, hypertrophic cardiomyopathy, short stature, sparse hair, Arnold-Chiari malformation, motor performance impairments, ectodermal manifestations, and intellectual delay.", "MENTAL RETARDATION, AUTOSOMAL DOMINANT 38": "Delayed psychomotor development, severe intellectual disability, lack of speech, dysmorphic facial features (small head circumference, deep-set eyes, downslanting palpebral fissures, depressed nasal bridge, low-set ears, tented upper lip, everted lower lip, downturned corners of the mouth), neonatal hypotonia, severely delayed walking, sleep disorder, autistic features, behavioral abnormalities, seizures (generalized tonic-clonic or spasms), abnormal EEG (multifocal sharp wave or spike/wave discharges, intermittent spike, polyspike, and irregular spike and wave discharges), mild cerebral atrophy on brain MRI.", "NOONAN SYNDROME 3, Noonan syndrome": "Clinical features of the rare genetic disorder described in the texts include: \n- Juvenile myelomonocytic leukemia-like myeloproliferative disorder\n- Atrial septal defect, ventricular septal defect, and valvular pulmonary stenosis\n- Dysmorphic facial features, short stature, webbed neck, and severe developmental delay\n- Macrocephaly and sagittal suture synostosis\n- Craniosynostosis, including closure of the sagittal and lamboidal sutures\n- Cognitive deficits and Chiari 1 malformation\n- Reduced growth, hypertelorism, epicanthic folds, ptosis, and hypoplastic nasal bridge\n- Cardiac defects, including dysplastic pulmonary valve and hypertrophy of the interventricular septum\n- Pterygium colli, prominent philtrum, high palate, and low-set and posteriorly rotated ears\n- Mild pectus excavatum and myocardiopathy leading to death in some cases\n- Pulmonary stenosis, patent ductus arteriosus, and deformity of the sternum\n- Elevated alkaline phosphatase levels and malignant schwannoma in some cases\n- Transmission through multiple generations and autosomal dominant inheritance\n- Pulmonary valvular dysplasia with thickened cusps and abnormal facies\n- Ophthalmologic abnormalities, including hypertelorism, ptosis, and refractive errors\n- Changes in facial appearance with age and short stature in adulthood\n- Gastrointestinal dysfunction, including poor feeding and foregut dysmotility\n- Craniofacial anomalies, coarctation of the aorta, and hypertrophic cardiomyopathy\n- Arnold-Chiari malformation and neuroblastoma in some cases\n- Short stature, congenital heart defects, and polyhydramnios in prenatal cases\n- Motor performance impairments, decreased muscle strength, and reduced endurance in daily life.", "INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC, CHRISTIANSON TYPE": "Clinical features of the rare genetic disorder include profoundly impaired intellectual development, mutism, grand mal epilepsy, limited life expectancy, craniofacial dysmorphism, ophthalmoplegia, truncal ataxia, microcephaly, absence of expressive verbal language, slow regression of walking ability, friendly demeanor, seizures, deceleration of head growth, happy demeanor with frequent smiling and episodes of unprovoked laughter, hyperkinetic movements, open mouth, drooling, swallowing difficulties, thin body habitus, long face with pointed jaw, profuse dribbling, poor growth capacity, variable ambulation, similarity to Angelman syndrome, lack of speech development, hypotonia, developmental regression, abnormal eye movements, involuntary movements, learning problems, cerebellar atrophy, prominent glutamine/glutamate peak, delayed psychomotor development, cognitive impairment, truncal ataxia, hypotonia, early onset of seizures, movement or balance disorders, happy demeanor, unprovoked laughter, autism-like features, abnormal eye movements, sleep problems, gastroesophageal reflux, hyperkinetic movements, high pain threshold, diverse presentations in female carriers, attenuated form with mild intellectual disability, language delay, normal gross motor development, postnatal microcephaly, strabismus, no ataxia or cerebellar symptoms, learning difficulties, writing difficulties, dyslexia, dysphasia, splice site mutation in the SLC9A6 gene, production of different transcripts, residual production of normal transcript.", "CONGENITAL CATARACTS, FACIAL DYSMORPHISM, AND NEUROPATHY": "CCFDN syndrome is a rare autosomal recessive disorder characterized by congenital cataracts, facial dysmorphism, and neuropathy. It is distinct from other similar disorders and affects both motor and intellectual development. Peripheral neuropathy, skeletal deformities, and cognitive deficits are also observed. Nerve biopsy shows hypomyelination and demyelination. Other features include short stature, hypogonadism, and ataxia. Some patients experience acute rhabdomyolysis. The disease progresses over time, leading to motor and sensory neuropathy. Physiotherapy can help improve motor disabilities.", "PROTEUS SYNDROME": "Clinical features of Proteus syndrome include partial gigantism of the hands and/or feet, nevi, hemihypertrophy, subcutaneous tumors, macrocephaly or other skull anomalies, accelerated growth, and visceral affections. Skin changes are papillomatous epidermal nevi. Abdominal and pelvic lipomatosis, conjunctival dermoid, and twisted necrotic mesenteric fat have been reported. Lesions follow the lines of Blaschko. Surgical removal of lymphatic, fatty, or hemangiomatous elements is difficult and results in unsightly scars and keloids. Skin manifestations include marked hypertrophy of the soles, large epidermal nevi, and linear macular lesions. Other features include testicular malignancy, regional manifestations, splenic hyperplasia, ocular manifestations, immune deficiency, meningiomas, and pulmonary embolism. Elattoproteus syndrome is an inverse form of Proteus syndrome characterized by lipohypoplasia and patchy dermal hypoplasia.", "CRANIOFACIAL DYSMORPHISM, SKELETAL ANOMALIES, AND MENTAL RETARDATION SYNDROME": "Clinical features of the rare genetic disorder include facial dysmorphism, multiple malformations of the vertebrae and ribs, mental retardation, enlarged cerebral ventricles and septum pellucidum, affable behavior, hypodensity of gray matter, hypertelorism, cleft lip/palate, severe intrauterine and postnatal growth failure, rectovaginal fistula, growth hormone deficiency, colobomas of the optic nerve, strabismus, ptosis, talipes, valgus deformity of feet, hypermobile joints, renal pelvic dilation, patent ductus arteriosus, hypotonia, poor feeding, craniofacial dysmorphisms, highly arched bushy eyebrows, synophrys, hypertelorism, broad nasal bridge, short nose, microdontism, gingival hyperplasia, pectus excavatum, scoliosis, vertebral fusion, rib anomalies, tall or short stature, global developmental delay, hyporeflexia, unsteady gait, intention tremor, genitourinary anomalies, spontaneous abortions, hypothyroidism, self-mutilating behavior, short neck, prognathism, hyperextensible fingers, pectus carinatum, genu varus, dysgenesis of the corpus callosum, cerebellar herniation, high birthweight, bilateral talipes equinovarus, grooved tongue tip, polyhydramnios, abnormal bladder, dysmorphisms, developmental delay, epilepsy, abnormal modeling and fusion of ribs, poor fetal movement, colpocephaly, dysgenesis of the corpus callosum, brachycephaly, flat facies, wide nasal bridge, delay of primary dentition, microdontism of primary teeth, micrognathia, Sprengel deformity, and pectus excavatum.", "PFEIFFER SYNDROME": "Clinical features of the rare genetic disorder include broad, short thumbs and big toes, triangular or trapezoid-shaped thumbs pointing outward, acrocephaly, polysyndactyly, enlarged thumbs and great toes with duplication, syndactyly, normal intelligence, variability of expression, Kleblattschaedel, severe manifestations, tracheal stenosis, cloverleaf skull anomaly, hearing loss, craniosynostosis, corneal scleralization, choanal stenosis, scoliosis, acanthosis nigricans, hydrocephalus, mental retardation, and bony ankyloses in various joints.", "Coffin-Siris syndrome": "Rare genetic disorder: Coffin-Siris syndrome (CSS)\nPhenotype characteristics:\n- Mental retardation\n- Absent or hypoplastic fifth fingernails/toenails and phalanx\n- Hypertrichosis (excessive hair growth)\n- Dysmorphic facial features (low anterior hairline, thick arched eyebrows, broad nose, thick lips)\n- Rough skin with hyperkeratotic plaques\n- Broad feet and fingertips\n- Short stature\n- Behavioral abnormalities (obsessive-compulsive disorder, withdrawal, stubbornness, autistic features)\n- Limited language with hoarse or high-pitched voice\n- Mild nail hypoplasia\n- Coarse facies\n- Additional features: myopia, strabismus, mild short stature, nail hypoplasia, ventricular septal defect, patent ductus arteriosus, coarctation of the aorta, hip dislocation, muscular hypotonia, abnormal head shape, low-set and abnormally shaped ears, downslanting palpebral fissures, bulbous nasal tip, thin upper lip, minor teeth anomalies, brachydactyly or single palmar creases, frequent infections, agenesis of the corpus callosum, severe speech delay, intellectual disability.", "LINEAR SKIN DEFECTS WITH MULTIPLE CONGENITAL ANOMALIES 1, Linear skin defects with multiple congenital anomalies": "Clinical features of the rare genetic disorder include irregular areas of erythematous skin hypoplasia on the head and neck, microphthalmia, corneal opacities, orbital cysts, and diaphragmatic hernia. Other characteristics may include absence of the septum pellucidum, depigmented patches of skin, unerupted wisdom teeth, cardiomyopathy, genital anomalies, short stature, and agenesis of the corpus callosum. The disorder is distinct from focal dermal hypoplasia and incontinentia pigmenti. It is associated with X Y translocations and terminal deletions of the X chromosome at Xp22.3 or Xp22.2. The disorder is predominantly seen in females, but there have been cases in XX males. X inactivation may play a role in determining the phenotype.", "DEAFNESS, ONYCHODYSTROPHY, OSTEODYSTROPHY, MENTAL RETARDATION, AND SEIZURES SYNDROME": "Rare genetic disorder: DOOR syndrome\nPhenotype characteristics:\n- Mental retardation\n- Perceptive deafness\n- Dysplasia of fingernails\n- Triphalangeal thumbs\n- Hypoplasia of terminal phalanges\n- 'Decapsalidic' fingerprints (arch pattern on each finger)\n- Absence of distal phalanges and nails of all digits\n- Cystic dysplasia of kidneys\n- Dilated right cerebral ventricle\n- Convulsions\n- Large nose with wide nasal tip\n- Developmental delay\n- Severe sensorineural deafness\n- Abnormal nails and phalanges\n- Onychodystrophy\n- Osteodystrophy\n- Microcephaly\n- Global developmental retardation\n- Progressive blindness\n- Seizures (associated with hypsarrhythmia)\n- Markedly reduced myelination in brain\n- Increased 2-oxoglutarate in urine\n- Genetic heterogeneity\n- Lower levels of 2-oxoglutarate decarboxylase activity\n- Coarse facial features\n- Congenital cardiac defect (in some cases)\n- Increased urinary 2-oxoglutaric acid and 2-hydroxyglutaric acid\n- Poor feeding\n- Recurrent respiratory infections\n- Profound deafness\n- Malformations of nails and digits\n- Mental retardation\n- Coarse facial features\n- Ophthalmologic anomalies\n- Neurologic abnormalities (neonatal hypotonia, seizures, peripheral neuropathy)\n- Dental, renal, and cardiac anomalies (less common)\n- Progressive course with early childhood mortality (seizures or respiratory distress)\n- Neurometabolic etiology\n- Speech delay\n- Malformations of nails and digits\n- Mild neurologic involvement\n- Developmental delay and intellectual disability\n- Seizures (various types)\n- Increased urinary 2-oxoglutaric acid (in some cases)", "EHLERS-DANLOS SYNDROME, SPONDYLODYSPLASTIC TYPE, 2": "Patients with EDSSPD2 exhibit a severe form of Ehler-Danlos syndrome and spondyloepimetaphyseal dysplasia. Key clinical features include severe skeletal dysplasia, postnatal growth restriction, kyphoscoliosis, joint contractures and hypermobility, congenital hip dysplasia, cervical spine instability, hypotonia, hyperextensible and soft skin, atrophic scarring, recognizable facies, delayed motor and speech development, and various cardiovascular complications. Radiographic findings include spondyloepimetaphyseal dysplasia, metaphyseal widening, diaphyseal narrowing and bowing, iliac bone hypoplasia, vertebral body shape changes, acetabular and femoral head dysplasia, and osteopenia.", "MENTAL RETARDATION, AUTOSOMAL RECESSIVE 39": "1. Langouet et al (2013):\n- Impaired intellectual development and behavioral problems\n- Delayed psychomotor development and severe speech delay\n- Microcephaly, short stature, kyphoscoliosis, and dysmorphic facial features\n- Behavioral abnormalities including hyperactivity, aggression, and stereotypic movements\n- Mild lymphopenia of naive T cells\n\n2. Ziegler et al (2019):\n- Severely impaired intellectual development, progressive microcephaly, scoliosis, and sleep disorders\n- Self-injurious behavior and partial ovarian failure in one patient\n- Hypoplastic corpus callosum and dysmorphic facial features\n- Periodic limb movement disorder, intermittent esotropia, and hypermetropia in the second patient\n- Prominent extra-axial fluid, ventriculomegaly, and decreased deep white matter volume on MRI\n- Presence of pubic hair on the labia at a young age", "GONADAL DYSGENESIS, DYSMORPHIC FACIES, RETINAL DYSTROPHY, AND MYOPATHY": "Clinical features of the rare genetic disorder include peculiar facies, cardiac and renal anomalies, musculoskeletal abnormalities, ectodermal defects, short stature, streak gonads, mild developmental delay, cleft lip and palate, preauricular pits, acromelia, hypermuscular appearance, punched out scalp defects, unusual hair whorls, squashed down nose, low-set ears, delayed bone age, ventricular septal defects, right renal agenesis, hypoplastic labia majora, facial dysmorphism, dry and scaly skin, lacrimal puncta hypoplasia, rod-cone dystrophy, myopathy, short broad hands, syndactyly, gastrointestinal anomalies, and cardiac anomalies.", "SEIZURES, SCOLIOSIS, AND MACROCEPHALY/MICROCEPHALY SYNDROME": "Clinical features of the rare genetic disorder include delayed psychomotor development, poor speech, seizures, macrocephaly, scoliosis, hypotonia, coarse facies with hypertelorism, skin sensitivity, low bone density, gastrointestinal abnormalities, cryptorchidism in males, brain hemorrhage, hematuria with proteinuria, wide-based gait, ventricular septal defect, hypertension, hepatic dysfunction, overlapping toes, tremor, microcephaly, poor feeding, constipation, neurologic regression, flat forehead, large ears, decayed teeth, gingival hypertrophy, autism, dysmorphic features, aggressive behavior, sleep difficulties, patent ductus arteriosus, thin corpus callosum, intellectual disability, repetitive/obsessive behavior, limited speech, hypotonic appearance, distal anomalies of the hands and feet, osteopenia, scoliosis, and multiple exostoses.", "NOONAN SYNDROME 5": "Rare autosomal dominant disorder with short stature, facial dysmorphism, and various congenital heart defects. Facial features include broad forehead, hypertelorism, downslanting palpebral fissures, high-arched palate, and low-set, posteriorly rotated ears.", "COHEN-GIBSON SYNDROME": "Clinical features of the rare genetic disorder include overgrowth, intellectual disability, delayed psychomotor development, speech delay, poor fine motor skills, seizures, macrocephaly, large ears, hypertelorism, downslanting palpebral fissures, retrognathia, myopia, cataracts, umbilical hernia, cryptorchidism, posttraumatic patellar dislocation, widely spaced nipples, pigmented nevi, large hands with camptodactyly, advanced bone age, scoliosis, abnormal flaring of distal clavicles, distal ribs, metaphyses of distal radius, distal ulna, distal femur, proximal tibia, flattened left acetabulum and femoral head, hypotonia, stiffness of joints and tendons, biomechanical variations of feet and knees, asymmetric skull, round face, abnormal bite, deep-set eyes, almond-shaped palpebral fissures, prominent nasal root and nasal bridge, bifid uvula, large hands with long slender fingers, large slender feet, numerous pigmented nevi, C1-C2 spinal instability, traumatic spinal cord compression, growth above the 97th percentile, restricted range of movement of certain large joints, increased birth weight, length, and head circumference, cleft palate, posterior ear pits, capillary hemangioma of the back, nephromegaly, tracheomalacia, patent ductus arteriosus, atrial septal defect, mitral regurgitation, inguinal and femoral hernias, white matter volume loss, thinning of the corpus callosum, cervical spine stenosis, small iliac wings, coxa valga, wide metaphyses, osteopenia, Achilles tendon and hamstring contractures, chondromalacia, recurrent dislocation and subluxation of the patellae, pes planovalgus, abnormal gait, dysmorphic facial features, visual disturbances, long broad palms, long fingers, broad thumbs, small nails, joint laxity of small joints of hands, broad forehead, long philtrum, low nasal bridge, epicanthus, delayed psychomotor development, low IQ, flexion disorder of metacarpophalangeal joints, and umbilical hernia.", "RAFIQ SYNDROME": "Rare genetic disorder: Rafiq Syndrome/MAN1B1-CDG. Clinical features include severely impaired intellectual development (IQ<40), delayed speech, truncal obesity, epilepsy, dysmorphic features (downslanting palpebral fissures, broad nose, small chin), hyperphagia, delayed psychomotor development, aggression, dolichocephaly, hypertelorism, flat philtrum, seizures, hypotonia, joint hypermobility, inverted nipples, skin laxity, cerebellar hypoplasia, abnormal fat distribution, macrocephaly, abnormal liver function.", "INTELLECTUAL DEVELOPMENTAL DISORDER WITH SHORT STATURE, FACIAL ANOMALIES, AND SPEECH DEFECTS": "Clinical features of the rare genetic disorder include short stature, obesity, bulbous nasal tip, microretrognathia, brachydactyly, joint hyperlaxity, and dislocations. Severe mental retardation, delayed or slurred speech, and global developmental delay are also observed. Dysmorphic features include a large bulbous nose and variable microretrognathia. Some individuals may have strabismus, microcephaly, or behavioral problems. Skeletal abnormalities are present in some cases, while others show no skeletal anomalies.", "MANDIBULOFACIAL DYSOSTOSIS, GUION-ALMEIDA TYPE": "Clinical features of the rare genetic disorder include mental and growth retardation, microcephaly, trigonocephaly, preauricular skin tags, cleft palate, zygomatic arch hypoplasia, accentuated micrognathia, severe language and speech delay, esophageal atresia, distal tracheoesophageal fistula, low-set right ear with microtia, glossoptosis, congenital radioulnar synostosis, hypoplasia of the zygomatic arch, cup-shaped ears, congenital heart defects, facial dysmorphism, delayed psychomotor development, conductive hearing loss, choanal atresia, pulmonary stenosis, atrial septal defect, delayed myelination, retarded bone age, seizures, short neck, slender fingers, and delayed walking. Mutations in the EFTUD2 gene were identified in some patients.", "JOUBERT SYNDROME 36": "Patients with this rare genetic disorder present with global developmental delay, hypotonia, ocular movement abnormalities (strabismus, ptosis, oculomotor apraxia), and mesoaxial polydactyly. Additional features may include lusterless hair, midline cleft lip or high-arched palate, Y-shaped metacarpals, mild sensorineural deafness, macrocephaly, and Joubert facies. Brain imaging can show a range of findings, including the classic \"molar tooth sign\" characteristic of Joubert syndrome.", "YWHAZ": "The 14-3-3 proteins are highly conserved and found in plants and mammals. They activate c-Raf through the protein kinase C signaling pathway. The zeta isoform of 14-3-3 is widely expressed in various brain regions and shares high sequence homology with other subtypes. It has phospholipase A2 activity.", "EIF5A": "Patients in the study exhibited developmental delay or impaired intellectual development, microcephaly, and facial dysmorphisms. Facial dysmorphisms included supraorbital ridge hypoplasia or prominence, micrognathia, low-set or prominent ears, broad eyebrows, epicanthus, bulbous nasal tip, and thin upper lip. Most patients had microcephaly and varying degrees of developmental delay. Some patients also had motor and speech delays. Three patients had cardiac anomalies, including atrial septal defect, dysplastic tricuspid valve with regurgitation, and bicuspid aortic valve. Neonatal feeding difficulties were observed in four patients, with two requiring a gastrostomy tube for feeding.", "FLOATING-HARBOR SYNDROME": "Floating-Harbor syndrome is characterized by short stature with delayed bone age, expressive language delay, and a triangular face with a prominent nose and deep-set eyes. Other common features include low hairline, thin lips, posteriorly positioned ears, and mild to moderate mental retardation. Some patients may also have celiac disease, brachyphalangy, clinodactyly, and behavioral problems. Growth hormone therapy may be used to treat short stature. Some patients may develop complications such as arthritis, hypertension, intramedullary ganglioglioma, or tethered spinal cord.", "MYASTHENIC SYNDROME, CONGENITAL, 19": "Clinical features of the rare genetic disorder include:\n- Onset of congenital myasthenic syndrome soon after birth\n- Respiratory insufficiency, hypotonia, and feeding difficulties\n- Muscle weakness, including ptosis, poor head control, and limb hypotonia\n- Delayed cognitive development and learning difficulties\n- Dysmorphic features such as low-set ears, micrognathia, and high-arched palate\n- Muscle biopsy showing abnormal fiber size and central nuclei\n- Decremental response in repetitive nerve stimulation\n- Variable disease course, with some patients experiencing stable or improved symptoms and others declining in respiratory function\n- Nonfluctuating eyelid ptosis and weakness of facial, bulbar, respiratory, and axial muscles\n- Limb muscles less affected\n- Skeletal abnormalities such as pectus carinatum and scoliosis with kyphosis\n- Neurophysiology studies consistent with abnormal neuromuscular transmission.", "KAUFMAN OCULOCEREBROFACIAL SYNDROME": "Distinctive syndrome: growth retardation, microcephaly, mental retardation, hypertelorism, ptosis, upslanted palpebral fissures, microcornea, sparse eyebrows, flat philtrum, hypotonia, micrognathia, high palate, lordosis, constipation, flat feet. Additional features: conductive hearing loss, iris coloboma, postaxial polydactyly, aplasia of corpus callosum, preauricular tags, large clitoris, fine hair, thin skin, feeding difficulties, gastroesophageal reflux, low growth hormone levels, renal anomalies, low cholesterol levels. Syndrome named blepharophimosis-ptosis-intellectual-disability syndrome (BPIDS).", "INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC, SNIJDERS BLOK TYPE": "Clinical features of the rare genetic disorder include impaired intellectual development, variable neurologic features (such as hypotonia, movement disorders, and microcephaly), behavioral problems (including autism spectrum disorder, hyperactivity, and aggression), epilepsy, joint hyperlaxity, skin pigmentary abnormalities, cleft lip and/or palate, hearing and visual impairment, and precocious puberty. Dysmorphic facial features are noted but not consistent. Males may also exhibit mild to severe intellectual disability, movement disorders, behavior problems, and variable dysmorphic features. Brain imaging findings may include corpus callosum hypoplasia, ventricular enlargement, and cortical dysplasia. Other features may include macrocephaly, progressive spasticity, dysarthria, spastic paraparesis, tremor, learning disabilities, cardiac anomalies, ophthalmologic issues, and hearing problems. Central nervous system malformations may include polymicrogyria, corpus callosal hypodysgenesis, dysmorphic basal ganglia, small olfactory bulbs, and pontine and inferior vermis hypoplasia. Facial dysmorphisms may include short palpebral fissures, micrognathia, bulbous nasal tip, protruding ears, high-arched palate, thin upper vermilion, and smooth philtrum. Other features may include dystonia, cyclical vomiting syndrome, cutaneous mastocytosis, microcephaly, dolichocephaly, epicanthal folds, telecanthus, large ears, hypopigmented spots, dolichostenomelic appearance, joint hypermobility, long face with broad nasal bridge, anteverted nares, and pigmentary abnormalities. Brain MRI findings may include thin corpus callosum, prominent prepontine cistern, vertical clivus, and prominent ventricles.", "SULEIMAN-EL-HATTAB SYNDROME": "Rare genetic disorder: \n- Syndromic developmental disorder\n- Hypotonia, respiratory insufficiency, poor feeding\n- Global developmental delay, poor expressive speech\n- Delayed walking, poor motor skills, nonverbal\n- Cognitive impairment, limited ability to follow commands\n- Distinctive facial features: microcephaly, excessive forehead hair, arched eyebrows, hypertelorism, broad nasal bridge, thin upper lip, low-set prominent ears\n- Other features: respiratory infections, cardiovascular malformations, cryptorchidism, single palmar crease\n- Less common features: hirsutism, preauricular skin tag, webbed neck, microretrognathia, wide mouth, downslanted palpebral fissures\n- Additional features: drooling, seizures, short stature, brachycephaly, polydactyly, clinodactyly, hydronephrosis, hearing impairment, eye anomalies (hyperopia, strabismus, amblyopia, pale optic discs)", "INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 93": "XLID is a rare genetic disorder characterized by macrocephaly, intellectual impairment, and various physical features. Patients often have tall stature, obesity, undescended testes, and muscular hypotonia. Facial features include a long face, pointed chin, large and prominent ears, and a large and wide forehead. Neurodevelopmental delays, including motor and speech delays, are common. Some patients also exhibit autistic traits or shyness. Mild kyphosis or scoliosis may be present in some cases. Cryptorchidism and mild clinical features in mothers, such as macrocephaly and facial dysmorphism, are also observed. Neoplasia has not been reported in XLID patients.", "HYPOPARATHYROIDISM-RETARDATION-DYSMORPHISM SYNDROME": "Clinical features of the rare genetic disorder, congenital hypoparathyroidism, include growth and mental retardation, seizures, severe intrauterine and postnatal growth retardation, dysmorphic facial features (deep-set eyes, depressed nasal bridge, beaked nose, long philtrum, thin upper lip, micrognathia, large floppy earlobes), skeletal defects, reduced T-cell subsets, low birth weight, delayed bone age, and abnormal hormone levels (undetectable parathyroid hormone, low growth hormone, low insulin-like growth factor-1). Brain imaging may show hypoplasia of the anterior pituitary, infundibulum, and corpus callosum, as well as decreased white matter volume, delayed myelination, and dilated lateral ventricles. The disorder is often seen in children of consanguineous parents, particularly from the Middle East.", "DESBUQUOIS DYSPLASIA 2": "Rare genetic disorder: Short stature, progressive growth retardation, facial dysmorphism (synophrys, deep nasal ridges, full lips, puffy skin), macrocephaly, long philtrum, broad thumbs, clinodactyly, coxa valga, flat feet, acne, hirsutism, normal endocrine evaluation, mild skeletal changes, intellectual disability. \"Monkey wrench\" appearance of femoral neck, abnormal feet, truncal obesity, short extremities, dislocations, short long bones, advanced carpal and tarsal ossification, hypotonia, flat face, hyperlaxity, respiratory distress, knee dislocation, patellar dislocation, brachydactyly, brachymetacarpalia, stub thumbs, flat acetabular roofs, platyspondyly, cleft palate or bifid uvula, epicanthal folds, synophrys, cognitive developmental delay. Overlap with Desbuquois dysplasia.", "MICROPHTHALMIA, SYNDROMIC 2": "Clinical features of the rare genetic disorder, known as oculofaciocardiodental (OFCD) syndrome, include congenital cataracts, microphthalmia, long narrow face, dental abnormalities (radiculomegaly, delayed dentition, persistent primary teeth), cardiac anomalies (atrial and ventricular septal defects), and facial dysmorphism (high nasal bridge, cleft palate). Other associated features include hearing loss, syndactyly, skeletal anomalies, and feeding difficulties. Inheritance is suggested to be X-linked dominant with male lethality. Mutations in the BCOR gene have been identified in some cases.", "CRANIOSYNOSTOSIS 4": "Clinical features of the rare genetic disorder include lambdoid craniosynostosis, occipital flattening, posterior plagiocephaly, frontal bossing, hypertelorism, telecanthus, short nose with anteverted nostrils, small and low-set ears, microretrognathia, small hands and feet with horizontal nail ridges. Other characteristics include prominent scalp veins, unusual hair whorl, normal growth, development, hearing, and vision. Some individuals may have behavioral or learning problems, concentration and language acquisition issues, and Chiari type I malformations. Mutations in the ERF gene are associated with craniosynostosis, with fusion affecting various sutures. Delayed primary surgery is common, and extracranial growth is typically normal.", "OHDO SYNDROME, SBBYS VARIANT, GENITOPATELLAR SYNDROME": "Clinical features of the rare genetic disorder include congenital heart defects, hypothyroidism, mental retardation, facial dysmorphism (blepharophimosis, bulbous nose), absent/hypoplastic patellae, genital and renal anomalies, developmental delay, microcephaly, myopathic facies, macular degeneration, torticollis, talipes equinovarus, patella dislocation, delayed myelination, disturbed white matter integrity, multicystic kidneys, hydronephrosis, arthrogryposis, flexion contractures, clubfeet, scrotal hypoplasia, cryptorchidism, absent scrotum, clitoral hypertrophy, prominent labia minora, anteriorly displaced anus, neuronal heterotopia, congenital heart disease, ureterohydronephrosis, multicystic kidney, radioulnar synostosis, hearing loss, osteoporosis, kyphoscoliosis, delayed puberty, upper airway edema, tracheostomy, bitemporal narrowing, ventriculomegaly, atrial septal defect, ventricular septal defect, patent ductus arteriosus, and radioulnar synostosis.", "DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 95": "Patients with DEE95, a rare genetic disorder, exhibit a range of clinical features. These include hypotonia, global developmental delay, hearing loss, visual impairment, intractable seizures (both febrile and nonfebrile), and coarse dysmorphic facial features. Other common characteristics include brachydactyly, ataxia, and balance problems. Brain imaging often reveals cerebellar atrophy and diffuse cortical atrophy. Additional features may include umbilical and inguinal hernia, cryptorchidism, pectus carinatum, hypoplastic distal phalanges, hepatomegaly, hip laxity, bulbous toes, and arthrogryposis. Microcephaly, abnormal brain MRI findings, renal malformation, visual impairment, hearing loss, and acquired arthrogryposis are also observed. Facial dysmorphisms include thick and arched eyebrows, almond-shaped palpebral fissures, depressed nasal bridge, and a deep philtrum. Some patients may experience complications associated with recurrent respiratory infections.", "LAMB-SHAFFER SYNDROME": "Rare genetic disorder: Haploinsufficiency of SOX5 gene. Phenotype characteristics include developmental delay, intellectual disability, speech delay, dysmorphisms (strabismus, frontal bossing, ear abnormalities, low nasal bridge), behavioral problems, seizures (in few cases), hypotonia, clumsiness, poor balance, articulation difficulties, scoliosis. Other features include poor early speech development, ritualistic behavior, constipation, expressive language delay, additional multisystem anomalies (renal agenesis, ureteral stenosis, optic nerve hypoplasia, laryngotracheomalacia, vertebral clefts), gestational diabetes (unknown teratogenic effect), delayed psychomotor development, mild dysmorphic features (blepharoptosis, low-set and posteriorly rotated ears, retrognathia, prominent maxilla, midline tongue groove, narrow palate with overcrowded teeth), nonprogressive optic atrophy, exotropia, mild myopia, mitral regurgitation, thoracic kyphoscoliosis, lumbar lordosis, pectus carinatum, marfanoid habitus, anxiety.", "INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 98": "Clinical features of the rare genetic disorder include:\n- Delayed psychomotor development\n- Absent or poor speech development\n- Postnatal growth retardation, often with microcephaly\n- Autistic behavioral features, such as stereotypic hand movements and repetitive behaviors\n- Strabismus\n- Additional variable features such as spasticity, axial hypotonia, seizures, drooling, gastroesophageal reflux, and lack of sphincter control\n- Dysmorphic features, including round face, short nose, short philtrum, and esotropia\n- Female carriers are unaffected\n- Dysmorphic features in affected males, including upswept hair, narrow forehead, downslanting eyebrows, long nose, hypoplastic alae nasi, thin lips, open mouth, and large ears\n- Developmental delay, limited speech, and refractory seizures in affected female carriers\n- Dysmorphic features in affected female carriers, including thick coarse hair, bitemporal narrowing, prominent nasal bridge, brachydactyly, a single transverse palmar crease, and fifth finger clinodactyly\n- Intellectual disability, seizures, and developmental delay in patients with de novo heterozygous mutations in the KIAA2022 gene\n- Intractable epilepsy with myoclonic and/or absence seizures, generalized seizures, and status epilepticus in patients with KIAA2022 mutations\n- EEG abnormalities, including polyspike waves, spike waves, focal discharges, and background slowing\n- Behavioral abnormalities, including autism, aggression, and hyperactivity\n- Variable features such as hypotonia, neonatal feeding difficulties, microcephaly, and mild nonspecific dysmorphic facial features\n- Severe global developmental delay, poor or absent speech, and early-onset intractable seizures in affected girls\n- Additional features in affected girls, including hypotonia, ataxic gait, autism, attention-deficit disorder, hyperactivity, and gastroesophageal reflux or constipation.", "SIX2": "The rare genetic disorder is characterized by strong SIX2 expression in skeletal muscle and weaker expression in pancreas. SIX2 is expressed in all fetal tissues except lung. In adults, SIX2 is expressed in skeletal muscle, pancreas, ovary, and sclera. It is not detected in other regions of the adult eye, optic nerve, heart, lung, kidney, liver, or breast.", "INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC, RAYMOND TYPE": "Rare genetic disorder: X-linked mental retardation with marfanoid habitus, pectus carinatum, pes planus, arachnodactyly, strabismus, prominent ears, fifth finger camptodactyly. Behavioral problems, schizophrenia, pyloric stenosis, hypotonia, cowlick, high forehead. Epilepsy, expressive communication deficits, hypoplasia of corpus callosum, decreased thalamic, caudate, putamen volumes. Global developmental delays, hypotonia. Mild cutaneous syndactyly, impaired intellectual development. Macrocephaly, downslanting palpebral fissures, upturned nose, speech and language delays. Macrocephaly, frontal bossing, deep-set eyes, underfolded helices, long nose, impaired intellectual development, obsessive behavior, autism spectrum disorder.", "OTOFACIOCERVICAL SYNDROME 2, WITH T-CELL DEFICIENCY": "Clinical features of the rare genetic disorder, otofaciocervical syndrome, include cup-shaped ears, bilateral mixed hearing loss, preauricular fistulas, lacrimal duct abnormalities, commissural lip clefting, retrognathia, protruding shoulders, and winged scapulae. Additional characteristics may include long eyelashes, blue sclerae, downslanting palpebral fissures, malocclusion, dental caries, clinodactyly, cutaneous syndactyly, vertebral abnormalities, periventricular white matter gliosis, and mastoiditis. Some individuals may also present with severe combined immunodeficiency (SCID), T-cell lymphopenia, and recurrent infections. Thymic hypoplasia or aplasia may be observed in some cases. Hematopoietic stem cell transplantation may be attempted for treatment.", "ALACRIMA, ACHALASIA, AND MENTAL RETARDATION SYNDROME": "Clinical features of the rare genetic disorder include alacrima, achalasia, and mental retardation. Patients present with feeding difficulties, delayed psychomotor development, and muscular hypotonia. Additional variable features include gait abnormalities, spasticity, nasal speech, visual problems, hearing impairment, and autonomic problems. Some patients may also have hyperkeratosis. There is clinical overlap with triple A syndrome, but no mutations in the AAAS gene were found. Facial dysmorphisms, short stature, and other physical abnormalities may also be present. One patient had neurofibromatosis type I with a known mutation in the NF1 gene.", "MICROCEPHALY-CAPILLARY MALFORMATION SYNDROME": "Clinical features of the rare genetic disorder include:\n- Microcephaly\n- Multiple capillary malformations of the skin\n- Dysmorphic facial features (whorled hair pattern, hypertelorism, ptosis, downturned mouth)\n- Abnormalities of the distal limbs (hypoplastic distal phalanges, brachydactyly, hypoplastic nails, displaced toes)\n- Intractable seizures and profound developmental delay\n- Variable features such as atrial or ventricular septal defect, hearing loss, and vesicoureteral reflux\n- Progressive cerebral atrophy, delayed myelination, thin corpus callosum on brain MRI\n- Severe microcephaly, failure to thrive, early-onset intractable seizures, severe developmental delay, and spasticity in some cases\n- Optic nerve atrophy, sloping forehead, broad nasal bridge, hypertelorism, and distal limb anomalies\n- Simplified gyral pattern and enlarged extraaxial space on brain imaging\n- Autosomal recessive inheritance pattern", "EHLERS-DANLOS SYNDROME, PERIODONTAL TYPE, 1": "Clinical features of this rare genetic disorder include skin lesions resembling necrobiosis lipoidica diabeticorum, periodontal disease leading to early loss of teeth, symmetrical patches on the front of the shins, small \"cigarette-paper scars\" on the knees, loose joints, bruisability, cutaneous fragility, marfanoid manifestations, arachnodactyly, tall stature, fragile skin, dental problems, alveolar bone loss, calculus formation, defect in type III collagen secretion, periodontal disease beginning at a young age, progressive periodontitis with tooth loss, premature aging features, intractable vasculitis, resorptive osteolysis, dislocated hip, urticaria, polyarthralgia, erosive arthritis, osteolysis, loss of skin elasticity, aortic and mitral regurgitation, reduced bone density, gingival disease, bruising, thin skin, joint hypermobility, poor quality gingival tissues, collagen disorganization, aneurysms, laryngeal pathology resulting in chronic hoarseness.", "SPASTIC PARAPLEGIA 47, AUTOSOMAL RECESSIVE": "Rare genetic disorder characterized by severe mental retardation, spasticity, microcephaly, muscular hypotonia progressing to hypertonia, hyperreflexia, spastic paraplegia, inability to walk unaided, cognitive deficit, speech delay, adaptive impairment, high palate, broad nasal bridge, short stature, hyperlaxity, genu recurvatum, pes planus, waddling gait, stereotypic laughter, shy character, absence of seizures, vision or hearing impairments, or anomalies of inner organs. Some cases also exhibit neurodegenerative symptoms, febrile seizures, dysarthria, spastic tongue protrusion, jaw opening with hypersalivation, thinning of corpus callosum, periventricular white matter changes, microcephaly, facial hypotonia, coarse face, bitemporal narrowing, bulbous nose, short philtrum, everted upper lip, wide mouth, high-arched palate, ventriculomegaly, white matter loss, contractures, valgosity of hips with acetabular dysplasia, clubfoot, open mouth, tongue protrusion, and broad nasal root.", "COLE-CARPENTER SYNDROME 1, Cole-Carpenter syndrome": "Rare genetic disorder resembling osteogenesis imperfecta (OI) with additional features of ocular proptosis, craniosynostosis, hydrocephalus, and distinctive facial characteristics. Recurrent diaphyseal fractures occur after the first birthday. Intellectual development is unaffected. Other symptoms include failure to thrive, macrocephaly, micrognathia, high-arched palate, low-set ears, small limbs, and bowing of lower limbs. No obvious fractures, normal serum calcium, phosphorus, and alkaline phosphatase levels. CT scans show ventriculoperitoneal shunt and sutural diastasis. Connective tissue disorder signs include osteopenia, pathologic fractures, discolored teeth, blue sclerae, and easy bruising. Severe progressive type of OI with multisutural craniosynostosis, growth failure, and craniofacial abnormalities. Wheelchair-bound with short stature, severe scoliosis, limb deformities, and low bone mineral density in adulthood. Normal serum levels of calcium, phosphorus, creatinine, alkaline phosphatase, and parathyroid hormone.", "OROFACIODIGITAL SYNDROME XVII": "Clinical features of the rare genetic disorder in the Indian girl and boy include: short stature, low weight, prominent forehead and nose, low-set ears with hearing loss, midline cleft lip, retrognathia, cleft tongue (girl), high-arched palate and nodular tongue (boy), multiple oral frenula (girl), multiple digital anomalies (bifid thumbs and great toes, short index fingers, polydactyly, Y-shaped central metacarpal), tetralogy of Fallot (boy), bilateral small kidneys (boy), hypomyelination of the corpus callosum and ventriculomegaly (boy), normal echocardiography, renal ultrasound, and brain MRI (girl), speech delay (boy), average academic ability (boy), global developmental delay with mild learning disability (girl). Y-shaped metacarpal is a characteristic feature of OFD6, while the face and hand abnormalities suggest Mohr syndrome (OFD2).", "NSD2": "Clinical features of the rare genetic disorder (possibly a subset of Wolf-Hirschhorn syndrome) include poor physical growth, hypotonia, small head circumference, mild intellectual disability, dysmorphic facial features (high forehead, hypertelorism, epicanthal folds, wide nasal bridge, protruding ears, clinodactyly), failure to thrive, short stature, developmental delay, behavioral abnormalities, almond-shaped eyes, upslanting palpebral fissures, arched eyebrows, flat nasal bridge, small chin, tooth enamel dystrophy, craniofacial asymmetry, micrognathia, high-arched eyebrows, widely spaced eyes, distinct mouth, abnormal teeth, and variable dysmorphic features. Seizures are not present in most cases. Mutations in the NSD2 gene are often present. The disorder is characterized by pre- and postnatal growth retardation, hypotonia, delayed walking, poor or absent speech, impaired intellectual development, learning difficulties, behavioral abnormalities, dysmorphic facial features (triangular face, broad forehead, retrognathia, low-set or posteriorly rotated ears, hypertelorism, deep-set eyes, arched eyebrows, broad or thin nasal bridge, bulbous nasal tip, thick lower lip, dental anomalies), and other features such as gastrointestinal disturbances and ocular refraction errors.", "GALLOWAY-MOWAT SYNDROME 3": "Galloway-Mowat syndrome (GAMOS) is a rare genetic disorder characterized by various clinical features. These include intrauterine growth retardation, microcephaly, oligohydramnios, hypotonia, sloping forehead, hypertelorism, epicanthal folds, microphthalmos, low-set floppy ears, small midface, high-arched palate, micrognathia, developmental delay, proteinuria, hypoalbuminemia, gyral abnormalities, frontal pachygyria, deficient myelination, dysmorphic features, failure to thrive, acquired microcephaly, severely delayed psychomotor development, renal tubulopathy, decreased serum magnesium, upturned nose, downward slanting palpebral fissures, high-arched palate, microphthalmia, nystagmus, strabismus, pectus excavatum, cryptorchidism, cerebellar atrophy, nonspecific leukodystrophy, hypoplastic left heart, aortic coarctation, coloboma, arachnodactyly, and ichthyosis. Most patients develop nephrotic syndrome, primary microcephaly, developmental delay, seizures, hypotonia, and spasticity. Brain imaging shows variable abnormalities. Prenatal findings include oligohydramnios, intrauterine growth retardation, and brain abnormalities.", "OROFACIODIGITAL SYNDROME XIV": "Text 1: Severe orofaciodigital syndrome with microcephaly, facial dysmorphisms, cleft palate, supernumerary teeth, polydactyly, micropenis, intellectual disability, and retinopathy. Brain imaging showed vermian hypoplasia, corpus callosum hypoplasia, subarachnoid cysts, and incomplete myelination.\n\nText 2: Skeletal ciliopathy with Dandy-Walker malformation, facial dysmorphisms, polydactyly, renal cysts, short ribs, and high-arched palate. Brain autopsy showed holoprosencephaly, cerebellar hypoplasia, and hydrocephalus. Clinical overlap with orofaciodigital syndrome and short-rib thoracic dysplasia syndromes.\n\nText 3: Ciliopathy pedigrees with microcephaly, orofacial clefting, retinal colobomas, polydactyly, cryptorchidism, and hypotonia. Brain abnormalities included Dandy-Walker malformation, molar tooth sign, and gray matter heterotopia. Renal and cardiac abnormalities also observed.\n\nNote: Each text has been summarized within 30 tokens.", "FACIAL PALSY, CONGENITAL, WITH PTOSIS AND VELOPHARYNGEAL DYSFUNCTION": "Clinical features of this rare genetic disorder include congenital nonprogressive bilateral facial palsy, velopharyngeal dysfunction, varying degrees of hypomimia, rhinophonia, impaired gag reflex, and bilateral ptosis. The severity of the disorder varies among individuals, with some having mild symptoms such as reduced upper lip movement or gag reflex, while others experience more severe symptoms like impaired facial movement and ptosis. There are no additional neurological, skeletal, muscular, or cognitive abnormalities associated with this disorder. The phenotype is nonprogressive, and some patients may experience improved symptoms with age or speech therapy. Brain imaging in affected individuals shows no abnormalities.", "COFFIN-SIRIS SYNDROME 9": "Coffin-Siris syndrome (CSS): Dysmorphic facial features, microcephaly, growth deficiency, hypoplastic fifth toenails, mild intellectual disability. Common features include hypertrichosis, arched eyebrows, low-set and posteriorly rotated ears, and full cheeks. Other characteristics include midface hypoplasia, short palpebral fissures, long eyelashes, low nasal root, shortened nose, short philtrum, open mouth, full lips, and hypoplastic distal phalanges with nail hypoplasia. Short stature, small kidneys, and delayed development may also be present. In some cases, patients may have normal skeletal survey and delayed bone age. CSS-like syndrome: Hypotonia, cognitive impairment, hypoplastic nails, short philtrum, low-set ears, sparse scalp hair, ocular motor apraxia, and speech impairment. IDDMOH: Microcephaly, ocular motor apraxia, abnormal eye morphology, and hypogonadotropic hypogonadism.", "TRICHORHINOPHALANGEAL SYNDROME, TYPE I, Trichorhinophalangeal syndrome": "Clinical features of the rare genetic disorder described in the texts include thin and slowly growing hair, pear-shaped nose with high philtrum, brachyphalangy with finger deformation and wedge-shaped epiphyses. Other characteristics include supernumerary incisors, pseudo-pseudohypoparathyroidism, TRPS1 in multiple generations, adult-onset chronic joint pain, facial and skeletal abnormalities, brachydactyly, cone-shaped epiphyses, spastic paraplegia, dysarthria, low-normal intellectual capacity, and skeletal abnormalities of the hands and feet. The disorder is associated with mutations in the SACS gene and TRPS1 gene, resulting in autosomal recessive spastic ataxia-6 and type I trichorhinophalangeal syndrome, respectively.", "NANCE-HORAN SYNDROME": "Rare genetic disorder: Nance-Horan syndrome. Affected males have dense nuclear cataracts and microcornea. Carrier females may have posterior Y-sutural cataracts and small corneas. Dental anomalies observed in affected individuals, including Hutchinsonian incisors, supernumerary teeth, and screwdriver incisors. Other features include prominent anteverted pinnae, short metacarpals, large ears and nose, and high nasal bridge. Intellectual handicap or developmental delay may be present in some affected males. Severe visual impairment leads to nystagmus and strabismus.", "FOCAL FACIAL DERMAL DYSPLASIA 3, SETLEIS TYPE": "Clinical features of Setleis syndrome include an aged leonine appearance, absent or multiple rows of eyelashes, upward-slanting eyebrows, rubbery nose and chin, temporal marks, periorbital puffiness, flattened nasal bridge, redundant facial soft tissue, and normal growth and development. Some patients may have imperforate anus. Additional manifestations may include aberrant hair pattern, linear skin lesions, short palpebral fissures, skin tag, cone-shaped teeth, pectus carinatum, and abnormal dermatoglyphic patterns. Facial characteristics become more pronounced with age. Some individuals may also have bitemporal scar-like lesions, low frontal hairline, whorled hair, thin lateral eyebrows, paucity of lower eyelashes, bulbous nasal tip, prominent lips, and horizontal chin furrow.", "CRISPONI/COLD-INDUCED SWEATING SYNDROME 1, Cold-induced sweating syndrome": "Clinical features of the rare genetic disorder include profuse sweating in response to cold temperatures, high palate, inability to fully extend elbows, kyphoscoliosis, feeding difficulties, reduced pain and temperature sensitivity, camptodactyly, facial muscle contractions, trismus, hyperthermia, respiratory distress, dysmorphic facial features, developmental delay, scoliosis, dental abnormalities, and decreased pain perception. The disorder is often observed in consanguineous families and has variable severity and age of onset.", "FACIAL PARESIS, HEREDITARY CONGENITAL, 3": "Rare genetic disorder: HCFP3\nClinical features:\n- Bilateral facial weakness\n- Sensorineural hearing loss\n- Esotropia\n- Feeding difficulties and speech delays\n- High hyperopia and need for glasses\n- Absence of facial nerve and abnormal cochlear function\n- Midface retrusion, low-set ears, upturned nasal tip, smooth philtrum\n- Intact taste discrimination, salivation, and lacrimation\n- Normal neurologic development\n- Dysmorphic facial features, including masked facies, lagophthalmos, flat nasal bridge\n- Oral dysfunction, including feeding and swallowing difficulties, speech delay\n- External auricular malformations", "Kabuki syndrome": "Clinical features of Kabuki syndrome include:\n1. Peculiar facial characteristics: eversion of lower lateral eyelid, arched eyebrows, depressed nasal tip, prominent ears.\n2. Skeletal anomalies: brachydactyly V, spinal deformity, cleft vertebrae.\n3. Dermatoglyphic abnormalities: increased digital ulnar loop, hypothenar loop patterns, absence of digital triradius c and/or d, fingertip pads.\n4. Mild to moderate mental retardation.\n5. Postnatal growth deficiency.\n6. Fetal finger pads.\n7. Congenital heart defects.\n8. Early breast development in some infant girls.\n9. Autosomal dominant inheritance with variable expressivity.\n10. Variable additional features: cleft palate, diaphragmatic hernia, hepatic anomalies, hearing loss, oral manifestations, behavioral phenotype, immune deficiency, and others.", "WIEDEMANN-STEINER SYNDROME, Kabuki syndrome": "Clinical features of this rare genetic disorder include pre- and postnatal growth deficiency, psychomotor delay, round and flat face, short nose, hypertelorism, long philtrum, short palpebral fissures, low-set ears, high-arched palate, alternating convergent squint, dilatation of renal calyces, short and thick limbs, hairy elbows, short stature, rhizomelic shortening of limbs, heavy jaw, downslanting palpebral fissures, mild hypertelorism, short nose with thick alae, facial asymmetry, developmental delay, delayed speech, hypertrichosis of distal-lateral arms and proximal-lateral forearms, hypotonia, left-sided hypoplasia, left ptosis, epicanthal folds, highly arched palate, hairy elbows with localized hypertrichosis, triangular and asymmetric face, microcephaly, thin upper lip, big anteverted ears, webbed neck, mental retardation, thick eyebrows with synophrys, short fingers and/or toes with short middle phalanges and clinodactyly V, hypotonia, failure to thrive, seizures, thick eyebrows, long eyelashes, generalized hirsutism, postnatal growth retardation, developmental delay, intellectual disability, broad nasal bridge with depressed nasal tip, thin upper vermilion borders, clinodactyly, fleshy hands, hypotonia in infancy, hepatic anomalies, diaphragmatic hernia, stenosis of central airways, lower lip pits, anorectal anomalies, retinal coloboma, avoidance of eye contact, love of music, failure to thrive progressing to obesity, and decreased IgA levels.", "CORPUS CALLOSUM, AGENESIS OF, WITH FACIAL ANOMALIES AND ROBIN SEQUENCE": "Rare genetic disorder with mental retardation, agenesis of corpus callosum, growth delay, cardiac defects (usually septal), limb defects, and urogenital anomalies in males. Facial dysmorphism includes micrognathia, full cheeks, hypertelorism, flattened nasal bridge, anteverted nares, and short neck. Additional features like anal anomalies or hernias may be present.", "HENNEKAM LYMPHANGIECTASIA-LYMPHEDEMA SYNDROME 3": "Text 1: Congenital lymphedema of lower extremities, polyhydramnios, hydroceles, widespread lymphedema, more severe in dependent areas and left leg, minimal facial edema, dysmorphic features (flat face, synophrys, hypertelorism, strabismus, upslanting palpebral fissures, anteverted peaked nostrils), protein-losing enteropathy, growth hormone deficiency, resolution of lymphedema during febrile illnesses, no developmental delay, hepatosplenomegaly, or major skeletal defects.\n\nText 2: Hydrops fetalis, dysmorphic facial features, omphalocele, pitting edema, wide-set eyes with short palpebral fissures and epicanthal folds, low-set ears, small nose, long philtrum, prominent upper lip, micrognathia, widely spaced nipples, tetramelic brachydactyly, umbilical hernia, small atrial septal defect, patent ductus arteriosus, patent foramen ovale, respiratory decompensation, autopsy findings of diffuse lymphatic malformation with tortuous thick-walled lymphatic channels in bowel mesentery and dilated hilar lymphatics of the kidney.", "OTOPALATODIGITAL SYNDROME, TYPE I": "Clinical features of the rare genetic disorder, fronto-otopalatodigital osteodysplasia (FOD), include conduction deafness, cleft palate, characteristic facies, generalized bone dysplasia, broad nasal root, wide-spacing of toes, conductive hearing loss, broad thumbs and great toes, short fingernails, fifth finger clinodactyly, dislocation of the head of the radius, pectus excavatum, mild dwarfism, secondary ossification center at the base of the second metacarpal and metatarsal, hypertelorism, median frontal prominence, heterozygote changes in radiographs of hands and feet, scoliosis, Larsen syndrome-like manifestations, long second metacarpal and fifth metatarsal, extracarpal bones, mental retardation (not in all cases), anomalies of the central nervous system, frontometaphyseal dysplasia, similarities to Melnick-Needles syndrome, Yunis-Varon syndrome, type III atelosteogenesis, and boomerang dysplasia.", "MOEBIUS SYNDROME; MBS": "Rare genetic disorder: Moebius syndrome\n- Congenital facial palsy with impaired ocular abduction\n- Involvement of facial nerve (CN VII) and abducens nerve (CN VI)\n- Orofacial dysmorphism and limb malformations\n- Mental retardation in some cases\n- Sporadic cases, but familial occurrence reported\n- Controversial diagnostic criteria, often confused with hereditary congenital facial paresis (HCFP)\n- Moebius syndrome is a complex developmental disorder of the brainstem\n- Limited eye abduction, hearing loss, cranial nerve dysfunction, motor and musculoskeletal problems\n- Neuropsychiatric findings reported", "CARDIOFACIOCUTANEOUS SYNDROME 3": "CFC3: Craniofacial features, ectodermal abnormalities, pulmonic stenosis, hypertrophic cardiomyopathy, failure to thrive, scoliosis, pectus excavatum, skeletal demineralization, ocular nystagmus, cerebral atrophy, seizures, developmental delay, hypotonia, heat intolerance, excessive sweating.\n\nCostello syndrome: Negative for HRAS mutation, BRAF or MEK1 mutations identified, clinical differences from HRAS mutation patients, polyhydramnios, ulnar deviation, growth hormone deficiency, tachycardia (HRAS), cardiovascular malformations (BRAF/MEK1), papilloma development, failure to thrive, short stature, hepatoblastoma (MEK1).\n\nCFC syndrome: Phenotypic overlap with Costello syndrome, MAP2K1 mutation-specific features, macrostomia, horizontal palpebral fissures.", "3MC SYNDROME 2": "Clinical features of the rare genetic disorder, referred to as Carnevale syndrome or 3MC syndrome, include eyelid ptosis, convergent strabismus, partial agenesis of abdominal muscles, hip dislocation, cryptorchidism, developmental delay, blepharophimosis, epicanthus inversus, craniosynostosis, telecanthus, cleft lip and palate, skeletal defects, hearing loss, facial dysmorphism, low-set ears, accessory nipples, tuberous angioma, supraumbilical depression, short fifth fingers, broad feet, axial hypotonia, psychomotor retardation, and conductive hearing loss. The syndrome may represent a single recessive spectrum rather than separate disorders.", "CENTRAL HYPOVENTILATION SYNDROME, CONGENITAL, 1": "Clinical features of congenital central hypoventilation syndrome (CCHS) include failure of autonomic control of ventilation during sleep, Hirschsprung disease (aganglionic megacolon), reduced esophageal motility and heart rate control, and possibly distinctive facial features. Other symptoms may include constipation, feeding difficulty, pupillary abnormalities, decreased perception of discomfort and anxiety, profuse sweating, and decreased basal body temperature. Some patients may present with respiratory symptoms, cognitive impairment, and cardiac anomalies. Molecular analysis often reveals pathogenic variants in the PHOX2B gene. Treatment may involve ventilatory support, tracheostomy, and surgical interventions for associated conditions.", "OROFACIODIGITAL SYNDROME V": "Clinical features of the rare genetic disorder include postaxial polydactyly, median cleft of the upper lip, lobulated tongue, frontal bossing, intellectual disability, cleft palate, cardiac anomalies, Hirschsprung disease, tongue hamartomas, low-set ears, microcephaly, developmental delay, feeding difficulties, bifid tongue, downslanting palpebral fissures, hypotonia, ataxia, auditory loss, joint laxity, high-arched palate, hypodontia, brain abnormalities, facial asymmetry, abnormal mandible, cerebellar vermis hypoplasia, eye abnormalities, epilepsy, impaired intellectual development, and cutaneous syndactyly.", "WARSAW BREAKAGE SYNDROME": "Rare genetic disorder: Warsaw breakage syndrome/Warsaw syndrome\nPhenotype characteristics:\n- Severe pre- and postnatal growth retardation\n- Microcephaly\n- Facial dysmorphism (small and elongated face, narrow bifrontal diameter, jugular hypoplasia, bilateral epicanthal folds, relatively large mouth, cup-shaped ears)\n- High-arched palate\n- Coloboma of the right optic disc\n- Deafness\n- Ventricular septal defect\n- Clinodactyly of the fifth fingers\n- Syndactyly of the second and third toes\n- Abnormal skin pigmentation\n- Increased chromosomal breakage induced by mitomycin C and premature chromatid separation\n- Barely detectable levels of DDX11 protein\n- Hypotonia\n- Severe intellectual disability\n- Short nose, neck, and forehead\n- Single palmar crease on both hands\n- Cochlear abnormalities and sensorineural deafness\n- Cardiac defects (tetralogy of Fallot)\n- Craniofacial features (depressed nasal bridge, broad nasal tip, overhanging columella)\n- Elevated induced chromosome breakage\n- Cohesin defects (premature chromatid separation and premature centromere division)\n- Possible increased cancer risk in heterozygous carriers of DDX11 mutations (further research needed)", "CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IIC": "Clinical features of the rare genetic disorder described in these texts include:\n- Cutis laxa (wrinkly skin)\n- Multiple congenital anomalies\n- Dysmorphic facial features (short forehead, blepharophimosis, entropion, hypertelorism, etc.)\n- Skeletal abnormalities (camptodactyly, overriding toes, clubfeet, scoliosis, etc.)\n- Genitourinary abnormalities (undescended testicles, micropenis, hydronephrosis, etc.)\n- Cardiac abnormalities (patent foramen ovale, patent ductus arteriosus, tricuspid regurgitation, etc.)\n- Respiratory issues (asthma, frequent pneumonias)\n- Neurological findings (muscle weakness, positive Gowers sign)\n- Growth parameters may be low initially but may show catchup growth over time\n- Developmental delays (delayed standing, walking, speech)\n- Other features such as midline cleft palate, saggy cheeks, prominent veins, etc.", "CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IID": "Rare genetic disorder: Cutis laxa with abnormal fat distribution, cardiomyopathy, cataract. Phenotype characteristics include hypotonia, generalized cutis laxa, abnormal fat distribution, dysmorphic features, failure to thrive, marfanoid habitus, cardiomyopathy, long QT interval, microcephaly, speech and motor delay, sagging skin, late-closing fontanel, glycosylation abnormalities. Facial features include triangular face, short forehead, hypertelorism, low-set ears, beaked nose, short chin. Additional features may include clubfeet, joint contractures, micropenis, cryptorchidism, hernia, cardiac defects, seizures, and neurologic abnormalities.", "NOONAN SYNDROME 1, Noonan syndrome": "Noonan syndrome is characterized by various clinical features including webbing of the neck, coarctation of the aorta, cryptorchidism, pterygium colli, deformed sternum, myocardiopathy, pulmonary stenosis, patent ductus arteriosus, elevated alkaline phosphatase levels, seizures, anomalous upper lateral incisors, lymphedema, posterior cervical hygroma, cutaneous lymphangioma, craniofacial anomalies, hypertrophic cardiomyopathy, short stature, headache, Arnold-Chiari malformation, ECG abnormalities, congenital heart defects, and motor performance impairments.", "NOONAN SYNDROME 5, Noonan syndrome": "Rare genetic disorder: autosomal dominant, short stature, facial dysmorphism, congenital heart defects (pulmonary stenosis, patent ductus arteriosus), broad forehead, hypertelorism, downslanting palpebral fissures, high-arched palate, low-set posteriorly rotated ears, webbing of the neck, coarctation of the aorta, cryptorchidism, pterygium colli, deformed sternum, myocardiopathy, elevated alkaline phosphatase levels, malignant schwannoma, mother-to-offspring transmission, seizures, anomalous upper lateral incisors, Turner syndrome similarities, Noonan syndrome, LEOPARD syndrome, lymphedema, posterior cervical hygroma, cutaneous lymphangioma, nuchal cystic hygroma, testicular maldescent, ophthalmologic findings (hypertelorism, ptosis, strabismus, refractive errors), facial changes with age, normal size at birth, delayed puberty, adult height below third percentile, poor feeding, gastrointestinal dysfunction, Arnold-Chiari malformation, ECG abnormalities, short stature, congenital heart defects (pulmonary stenosis, atrial septal defect, hypertrophic cardiomyopathy), polyhydramnios, PTPN11 mutations, facial analysis technology, motor performance impairment.", "TRICHOHEPATOENTERIC SYNDROME 2": "Clinical features of the rare genetic disorder, Trichohepatoenteric Syndrome (THES), include intractable diarrhea, hair abnormalities (sparse, fragile, uncombable hair with trichorrhexis nodosa), facial dysmorphism (square forehead, prominent cheeks, broad nasal root), hepatomegaly, hypochromic microcytic anemia, and immunodeficiency. Other findings may include cryptitis, cryptic abscesses, and inflammation in the colon, as well as fibrosis in the liver. Some patients may also have cafe-au-lait spots and peg teeth. The disorder can present shortly after birth and may require total parenteral nutrition. Long-term survival on oral feeding is possible, but diarrhea may persist.", "LACRIMOAURICULODENTODIGITAL SYNDROME": "Clinical features of lacrimoauriculodentodigital (LADD) syndrome include lacrimal abnormalities (aplasia/hypoplasia of puncta and obstruction of nasal lacrimal ducts), auricular anomalies (cup-shaped pinnas and mixed hearing deficit), dental abnormalities (small/peg-shaped lateral maxillary incisors and enamel dysplasia), and digital anomalies (fifth finger clinodactyly, thumb abnormalities, and syndactyly). Other features may include salivary gland abnormalities, delayed tooth eruption, renal disease, facial dysmorphism, chest wall abnormalities, and limb defects. Ocular involvement is common, with tear gland aplasia/hypoplasia, lacrimal puncta/canaliculi abnormalities, and tear deficiency. Mutations in the FGFR2 gene have been associated with LADD syndrome.", "PINEAL HYPERPLASIA, INSULIN-RESISTANT DIABETES MELLITUS, AND SOMATIC ABNORMALITIES": "Rare genetic disorder: Clinical features include dental and skin abnormalities, abdominal distention, phallic enlargement, early dentition, coarse facies, hirsutism, precocious mental development, prognathism, thick fingernails, acanthosis nigricans, insulin-resistant diabetes, ketoacidosis, intercurrent infections, pineal hyperplasia. In some cases, abnormal teeth and nails are absent, and patients may live into adulthood. Point mutation in insulin receptor gene identified.", "VAN DER WOUDE SYNDROME 1": "Clinical features of the rare genetic disorder, known as van der Woude syndrome (VWS), include malformations of the lower lip, such as symmetrical lumps and pits. Cleft palate may also be present in affected individuals. The syndrome is inherited in an autosomal dominant manner, but there is variable expressivity, leading to different manifestations within families. Lip pits are the most common feature, present in 88% of affected individuals, while clefts of the lip and palate occur in 21%. Ankyloglossia (tongue-tie) may also be associated with VWS. Genetic analysis has identified mutations in the IRF6 gene in some families, confirming the diagnosis. The presence of lip pits in affected families is important for genetic counseling, as the recurrence risk of VWS is higher than that of nonsyndromic clefts.", "KABUKI SYNDROME 2, GENERALIZED EPILEPSY WITH FEBRILE SEIZURES PLUS, TYPE 2": "Kabuki syndrome: long palpebral fissures, lower eyelid eversion, intellectual disability, long halluces, sparse eyebrows, long eyelashes, strabismus, large ears, fetal fingertip pads, aortic coarctation, areolar fullness, hirsutism, mild developmental delay.\n\nKABUK2: feeding problems, hypoglycemia, motor delay, speech delay, impaired intellectual development, cardiovascular malformations, genitourinary anomalies, palate and dental anomalies, hearing loss, strabismus, recurrent infections, hyperinsulinism, seizures, joint hypermobility, ectodermal abnormalities.\n\nGEFS+: generalized tonic-clonic seizures, absence seizures, myoclonic seizures, atonic seizures, febrile seizures, normal neurologic examination and cognition, variable phenotype.\n\nFamilial Febrile Seizures 3A: simple febrile seizures, afebrile partial seizures, mesial temporal lobe origin, vegetative or experiential phenomena, unilateral mesial temporal sclerosis.", "MYOPATHY, CONGENITAL, BAILEY-BLOCH": "Rare genetic disorder: Native American myopathy\nClinical features:\n- Multiple congenital anomalies: cleft palate, micrognathia, talipes equinus, arthrogryposis\n- Weakness, ptosis, kyphosis/scoliosis\n- Malignant hyperthermia\n- Myopathic facies, dysmorphic features\n- Generalized muscle weakness, atrophy, joint contractures\n- Diminished reflexes, foot deformities, oral hypotonia\n- Progressive scoliosis, restrictive respiratory insufficiency\n- Delayed motor development, normal cognition\n- Muscle biopsy shows small fibers, fiber-type disproportion\n- Hypotonia, poor feeding, dysmorphic features in neonatal period\n- Proximal muscle weakness, Gowers sign, scoliosis, facial weakness\n- Nonspecific myopathic changes, fatty degeneration of muscles\n- Hypotonia, growth delay, cleft palate, dysmorphic features, kyphoscoliosis\n- Delayed motor development, no cognitive impairment\n- Variable features: respiratory insufficiency, short trunk, pectus excavatum\n- Initial clinical diagnoses: Moebius syndrome, Carey-Fineman-Ziter syndrome\n- Onset at birth, variable clinical severity\n- Congenital hypotonia, talipes, contractures, cleft/high palate\n- Feeding difficulties, respiratory difficulties\n- Mild to moderate limb weakness, proximal > distal involvement\n- Ptosis, facial weakness, joint laxity, scoliosis/kyphosis/spinal rigidity\n- Dental malocclusion, jaw prominence, malar hypoplasia\n- Speech delay/dysarthria, hearing loss\n- Cryptorchidism in males\n- Adverse reaction to general anesthetics\n- Myopathic changes in muscle biopsies.", "CORPUS CALLOSUM, AGENESIS OF, WITH FACIAL ANOMALIES AND ROBIN SEQUENCE, INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC, SNIJDERS BLOK TYPE": "Clinical features of the rare genetic disorder include impaired intellectual development, variable neurologic features (such as hypotonia, movement disorders, and microcephaly), behavioral problems (including autism spectrum disorder, hyperactivity, and aggression), epilepsy, joint hyperlaxity, skin pigmentary abnormalities, cleft lip and/or palate, hearing and visual impairment, precocious puberty, abnormal brain imaging findings, dysmorphic facial features, macrocephaly, progressive spasticity, dysarthria, spastic paraparesis, learning disabilities, brain MRI findings (such as prominent ventricles and white matter loss), congenital heart defects, involuntary movements, hearing and ophthalmologic issues, central nervous system malformations, scoliosis, astrocytoma, IUGR, hypotonia, sensorineural hearing loss, akinetic seizures, hand stereotypies, dystonia, cyclical vomiting syndrome, cutaneous mastocytosis, microcephaly, dolichocephaly, epicanthal folds, telecanthus, large ears, hypopigmented spots, joint hypermobility, and facial dysmorphic features (such as micrognathia, hypertelorism, flattened nasal bridge, anteverted nares, and short neck).", "CEREBELLOFACIODENTAL SYNDROME": "Rare genetic disorder: Neurodevelopmental disorder with microcephaly, delayed development, and variable intellectual disability. Craniofacial anomalies: wave-shaped palpebral fissures, sparse eyebrows and hair, low-set ears, dental malocclusion, and prominent upper incisors. Brain imaging: cerebellar hypoplasia, thin corpus callosum, enlarged ventricles, and possible hypoplastic pons. Radiographs: bialveolar protrusion, prominent alveolar processes, and taurodontism. Other features: scoliosis, short neck and trunk, slender long bones, tapering fingers. Some patients may have laryngeal stridor or laryngomalacia.", "CHARCOT-MARIE-TOOTH DISEASE, TYPE 4B3": "Text 1: Nakhro et al (2013) described three Korean sisters with a rare genetic disorder characterized by progressive demyelinating CMT. Clinical features included distal leg weakness, gait ataxia, muscle atrophy and weakness in upper and lower limbs, areflexia, distal sensory loss, pes planus, scoliosis, and reduced nerve conduction velocities. Two patients became wheelchair-bound in their mid-forties.\n\nText 2: Bohlega et al (2011) reported three adult brothers with a syndromic form of sensorimotor polyneuropathy. They had microcephaly, cognitive impairment, brain atrophy, distal lower extremity weakness and atrophy, upper limb involvement, distal sensory impairment, loss of reflexes, and reduced nerve conduction velocities. Additional features included strabismus, ophthalmoplegia, facial weakness, syndactyly, dysarthria, and urinary incontinence.", "ACTL6A": "ACTL6A and ACTL6B are two proteins encoded by cDNAs obtained from S. cerevisiae Act3. ACTL6A shares 83% identity with ACTL6B and both proteins contain an ATP/ADP-binding pocket and 2 nuclear localization signals. ACTL6A is expressed in the nuclei of transfected HeLa cells and is excluded from nucleoli. Wide expression of ACTL6A is detected in human tissues through RT-PCR and EST database analysis.", "MENTAL RETARDATION, AUTOSOMAL DOMINANT 23": "Clinical features of the rare genetic disorder include moderately to severely impaired intellectual development, delayed psychomotor development, poor speech development, behavioral abnormalities (obsessive-compulsive behavior, hand-flapping, features of autism), dysmorphic features (eyebrow anomalies, brachycephaly, low hairline, depressed nasal bridge, prominent high nasal root, tubular nose, upslanting palpebral fissures, long and smooth philtrum, micrognathia, thin upper lip, crowded teeth), chewing difficulties or dribbling, variable skeletal abnormalities (scoliosis, kyphosis, lordosis, leg-length discrepancies), absence of seizures, microcephaly, or growth retardation. Some patients also had features overlapping with 3p25 microdeletion syndrome. Two unrelated females with the disorder had delayed psychomotor development, delayed speech acquisition, and common dysmorphic features. Three unrelated patients with the disorder and moyamoya disease had bilateral moyamoya angiopathy, with one patient experiencing ischemic stroke and two having transient ischemic attacks. Rare variants in the SETD5 gene may predispose to moyamoya disease with or without developmental delay.", "DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 54": "DEE54 is characterized by delayed development, severe intellectual disability, and regression. Patients experience various types of seizures, including atonic, absence, myoclonic, tonic, and tonic-clonic seizures. EEG shows multiple abnormalities, such as spike and polyspike waves, slowing, slow spike waves, and paroxysmal fast activity. Other common features include hypotonia, microcephaly, autistic features, enlarged ventricles, myelination delay, and physical abnormalities like deep-set eyes, narrow palate, and short second digits.", "CONGENITAL ANOMALIES OF KIDNEY AND URINARY TRACT SYNDROME WITH OR WITHOUT HEARING LOSS, ABNORMAL EARS, OR DEVELOPMENTAL DELAY": "Clinical features of the rare genetic disorder include:\n- Kidney defects such as renal hypoplasia, dysplasia, ectopia, and horseshoe kidney\n- Urinary tract abnormalities including bifid ureter, small urethral valve, renal pelvis dilatation, and vesicoureteral reflux\n- Chronic kidney disease and end-stage renal disease requiring dialysis\n- Cryptorchidism in males\n- Global developmental delay, speech delay, motor delay, hearing impairment, hypotonia, and autism spectrum disorder\n- Dysmorphic facial features such as broad nasal bridge, anteverted nares, hypertelorism, strabismus, prominent philtrum, and thin upper lip\n- Abnormal outer ears that are low-set, hypoplastic, abnormally hemmed, and anteverted or crumpled\n- Other organ malformations including heart defects, neurologic abnormalities, and anal malposition\n- Deletions of several contiguous genes contributing to extrarenal symptoms\n- Truncating point mutations in the PBX1 gene leading to renal hypoplasia, deafness, scoliosis, developmental delay, growth retardation, and dysmorphic facial features\n- Pleiotropic developmental disorder associated with de novo heterozygous point mutations in the PBX1 gene, resulting in delayed development, poor growth, short stature, hypotonia, craniofacial anomalies, renal anomalies, and genital abnormalities.", "JANSEN-DE VRIES SYNDROME": "Neurodevelopmental disorder with intellectual disability, speech delay, behavioral problems (anxiety, ADHD, obsessive behavior, sensory integration problems, ASD), gastrointestinal difficulties, high pain threshold, hypersensitivity to sound, small hands (brachydactyly), short stature, hypotonia, broad-based gait, visual problems (myopia, hypermetropia, strabismus), dysmorphic facial features (broad forehead, low-set posteriorly rotated ears, upturned nose, broad mouth with thin upper lip).", "INFANTILE LIVER FAILURE SYNDROME 2": "Rare genetic disorder: Recurrent acute liver failure in infancy. Onset in first 2 years of life, triggered by febrile illness. Symptoms include vomiting, lethargy, increased liver enzymes, jaundice, coagulopathy. Some patients have secondary hyperammonemia, hypoglycemia, encephalopathy. Comorbid features include cardiomyopathy, autoimmune gastrointestinal disease, epilepsy. No deaths reported. Liver size/function normal between episodes. Biopsy shows microvesicular steatosis. Patient recovers with supportive care. Normal growth and development. Last episode 3 years ago.", "JOHANSON-BLIZZARD SYNDROME": "Clinical features of Johanson-Blizzard syndrome include aplasia or hypoplasia of the nasal alae, congenital deafness, hypothyroidism, postnatal growth retardation, malabsorption, mental retardation, midline ectodermal scalp defects, absent permanent teeth, urogenital abnormalities (such as double vagina and double uterus), imperforate anus, pancreatic exocrine insufficiency, abnormal brain development, anorectal abnormalities, colostomy, pancreatic dysplasia, diabetes mellitus, intrauterine growth retardation, situs inversus, malrotation of the small intestine, lethal congenital heart defects, dilated cardiomyopathy, atrial septal defect, and liver involvement.", "CSTB": "Rare genetic disorder: Unverricht-Lundborg disease. Clinical features include progressive myoclonus, mild mental deterioration, stimulus- and photo-sensitive myoclonus, generalized tonic-clonic seizures, loss of Purkinje cells, ataxia, dysarthria, mental changes, and EEG abnormalities. Phenytoin worsens symptoms, while valproic acid improves them. Different from Lafora body disease, intelligence is slightly affected and psychotic symptoms are absent. Some patients have a subclinical stage before onset. Ramsay Hunt syndrome is clinically similar. Pathological abnormalities found in sweat glands. Photosensitivity is characteristic, but absent in some cases. MRI shows brainstem and cerebellar abnormalities. Electrophysiologic profiles differ between Unverricht-Lundborg and Lafora disease.", "MICROCEPHALY 3, PRIMARY, AUTOSOMAL RECESSIVE": "Text 1: 6-year-old girl with primary microcephaly, delayed psychomotor development, mild muscular hypotonia, moderate to severe sensorineural hearing loss.\n\nText 2: Patient with poor growth, severe microcephaly, short stature, prominent eyes, conical-shaped and widely spaced teeth, mixed conductive sensorineural hearing loss, delayed developmental milestones, simplified gyral pattern, small frontal lobes, partial absence of corpus callosum.\n\nText 3: 6-year-old girl with severe progressive microcephaly, developmental delay, no dysmorphic features, normal brain MRI, unaffected triplet sisters.\n\nText 4: 11-year-old boy with MCPH3, progressive microcephaly, moderate learning difficulties, significant speech delay, behavioral problems (aggression, temper tantrums, overactivity, poor concentration, poor socialization), sloping forehead, prominent nose, 11 cafe-au-lait spots, normal brain imaging.", "NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA AND DYSMORPHIC FACIES": "Text 1: A 75-year-old girl with arthrogryposis, developmental delay, intellectual impairment, dysmorphic features (brachycephaly, micrognathia, thin upper lip, etc.), hypertrichosis, and one seizure.\n\nText 2: A 15-year-old girl with NEDHYDF, hypotonia, developmental delay, impaired intellectual development, seizures, dysmorphic features (blue sclerae, dolichocephaly, etc.), and generalized overgrowth.\n\nText 3: 11 unrelated patients with a syndromic neurodevelopmental disorder, global developmental delay, impaired motor/speech/intellectual development, autism traits, hypotonia, delayed walking/speech, dysmorphic features (tall forehead, deep-set eyes, etc.), skeletal anomalies, dry skin, congenital heart/renal defects, constipation, undescended testes, and a terminated pregnancy with multiple anomalies.", "MARFANOID-PROGEROID-LIPODYSTROPHY SYNDROME": "Clinical features of the rare genetic disorder include severe intrauterine growth retardation, long narrow hands and feet, mild arthrogryposis, extreme hyperlaxity of small joints, facial dysmorphism (macrocephaly, hypoplasia of facial bones, upward-slanting palpebral fissures, entropion), persistent growth retardation, thinness with atrophic loose skin and prominent scalp veins, widely open fontanels, dermal atrophy, anarchic and hyperplastic elastin network, hypoplastic collagen bundles, fibroblasts with granulous vesicles, severe gastroesophageal reflux, aortic root dilation, severe myopia, ectopia lentis, reduction in subcutaneous fat tissue, prominent facial lipodystrophy, arachnodactyly, lens subluxations, tall stature, arrested hydrocephalus, mitral valve prolapse, wide open anterior fontanel, scaphocephaly, proptosis, pectus excavatum, craniosynostosis, lumbosacral dural ectasia, and no annuloaortic ectasia.", "MACROCEPHALY, DYSMORPHIC FACIES, AND PSYCHOMOTOR RETARDATION": "Rare genetic disorder: Overgrowth, intellectual disability, macrocephaly, increased birth length/weight, delayed psychomotor development, hypotonia, seizures, dysmorphic features (tall stature, long limbs, frontal bossing, triangular long face, sparse eyebrows, hypertelorism, downslanting palpebral fissures, malar hypoplasia, prominent nasal bridge, high-arched palate, prognathism, macrotia, long neck), asymmetric thorax, kyphoscoliosis, joint laxity, flat feet, large hands with arachnodactyly, severe expressive language delay, ataxic gait, brain abnormalities (hydrocephalus, megalencephaly, cortical atrophy, ventriculomegaly), myopia, thick corpus callosum, metopic synostosis, ADHD, schizoaffective disorder, joint hyperlaxity, genu valgum, cubitus valgus, thoracolumbar scoliosis, dysmetria, hyperreflexia.", "GALLOWAY-MOWAT SYNDROME 1, Galloway-Mowat syndrome": "Clinical features of the rare genetic disorder include microcephaly, hiatus hernia, nephrotic syndrome, large and floppy ears, albuminuria, brain and kidney malformations, paraventricular heterotopias, hydrocephalus, glomerular kidney disease, proteinuria, developmental delay, minor facial anomalies, contractural arachnodactyly, congenital hypothyroidism, optic atrophy, facial dysmorphism, severe cerebellar atrophy, thin corpus callosum, cortical atrophy, nephrotic syndrome with collapsing focal segmental glomerulosclerosis, hypertrophic podocytes, interstitial fibrosis, and tubular dilations. Other features include intellectual disability, seizures, spastic quadriplegia, limited joint mobility, talipes foot deformities, ventricular dilatation, delayed myelination, Dandy-Walker malformation, hypopigmented nonitchy skin patches, short stature, ataxia, dystonia, proteinuria, optic atrophy, retinopathy, basal ganglia degeneration, roving nystagmus, visual impairment, irritability, extrapyramidal movements, seizures, cerebral atrophy, steroid-resistant proteinuria, renal failure, small brains with small sclerotic cerebella, thickened basement membrane, effacement of podocyte foot processes, fibrosis, and tubular atrophy. Clinical variability and absence of renal involvement in some cases have also been observed.", "NOONAN SYNDROME 8, Noonan syndrome": "Noonan syndrome-8 is characterized by distinctive facial features (macrocephaly, hypertelorism, downslanting palpebral fissures, ptosis, epicanthal folds, low-set ears), skin and hair anomalies, short stature, webbed neck, and cardiovascular abnormalities (hypertrophic cardiomyopathy, pulmonic stenosis, atrial septal defects). Some patients may have intellectual disability, perinatal abnormalities, and increased risk of leukemia. Other associated features include autoimmune disorders, learning difficulties, delayed speech, and eye abnormalities. The RIT1 gene is a major contributor to Noonan syndrome, with a high prevalence of cardiovascular manifestations and lymphatic problems.", "CURRARINO SYNDROME": "The Currarino syndrome is characterized by partial sacral agenesis, a presacral mass, and anorectal malformation. Symptoms include constipation, perianal sepsis, and ascending infections. Associated malformations include rectovaginal fistula, tethering of the cord, duplex ureter, and more. Malignant degeneration of the presacral teratoma can occur. Mutations in the HLXB9 gene cause hemisacrum, a specific category of sacrococcygeal anomalies. Reduced penetrance and genetic heterogeneity are observed.", "MICROCEPHALIC OSTEODYSPLASTIC PRIMORDIAL DWARFISM, TYPE I": "Clinical features of this rare genetic disorder include brachymelic primordial dwarfism, abnormal body proportions, short limbs, low and broad pelvis, dysplastic acetabulum, bowed and broad humeri and femora, agenesis of the corpus callosum, lissencephaly, micrencephaly, dysplasia of the osseous skeleton, microcephaly, facial dysmorphism, skeletal abnormalities, corneal clouding, severe central nervous system neuronal migration abnormalities, sparse hair, dry and aged-appearing skin, multiple joint contractures and dislocations, and various brain abnormalities such as hypoplastic frontal lobes and vermis agenesis. Autosomal recessive inheritance has been suggested. Life expectancy ranges from 2.5 to 18 months, with some cases surviving past 3 years.", "COFFIN-SIRIS SYNDROME 5, Coffin-Siris syndrome": "Clinical features of the rare genetic disorder, Coffin-Siris syndrome, include delayed psychomotor development, intellectual disability, absent speech, poor overall growth, short stature, microcephaly, dysmorphic facial features (coarse facies, low frontal hairline, thick eyebrows, long eyelashes, flat nasal bridge, broad nose, large mouth, thick lower vermilion, short philtrum, abnormal ears, and sparse scalp hair), hypoplasia of distal phalanges with nail hypoplasia, atrial septal defect, dextropositio cordis, small cerebellum, Dandy-Walker malformation, abnormal corpus callosum, long and slender fingers, dystrophic and hypoplastic toenails, seizures, absent or hypoplastic nails and terminal phalanx of the fifth finger, hypertrichosis, rough skin with hyperkeratotic plaques, broad feet and fingertips, mild short stature, myopia, strabismus, behavioral abnormalities (obsessive-compulsive disorder, withdrawal, stubborn and obstinate behavior, autistic features), limited language with hoarse or high-pitched voice, ventricular septal defect, patent ductus arteriosus, mild coarctation of the aorta, hip dislocation, moderate to severe psychomotor retardation, muscular hypotonia, expressive speech more severely affected than receptive function, abnormal head shape, low-set and abnormally shaped ears, downslanting palpebral fissures, bulbous nasal tip, thin upper lip, minor teeth anomalies, brachydactyly or single palmar creases, hirsutism, coarse facial appearance, frequent infections, severe speech delay, agenesis of the corpus callosum, and facial similarities in individuals with deletions involving ARID1B. The complete spectrum of the Coffin-Siris syndrome phenotype is still a subject of debate.", "DIABETES MELLITUS, NEONATAL, WITH CONGENITAL HYPOTHYROIDISM": "Rare genetic disorder: Neonatal Diabetes, Hypothyroidism, and Renal and Hepatic Involvement. Clinical features include neonatal nonimmune diabetes mellitus, severe congenital hypothyroidism, intrauterine growth retardation, facial anomalies, glaucoma, cholestasis, and polycystic kidneys. Liver disease progresses to fibrosis, while renal disease presents with large kidneys, multiple small cysts, and deficient corticomedullary junction differentiation. Other features include pancreatic exocrine insufficiency, portal hypertension, osteopenia, skeletal abnormalities, facial dysmorphism, developmental delay, and sensorineural deafness.", "MELNICK-NEEDLES SYNDROME": "Clinical features of Melnick-Needles syndrome include typical facies (exophthalmos, full cheeks, micrognathia), flaring of long bone metaphyses, s-like curvature of leg bones, rib constrictions, and skull base sclerosis. Ureteral obstruction and contracted pelvis may occur. Females may have frontometaphyseal dysplasia, while males may have a lethal form. Other features include small chest, prominent forehead, high vertebrae, and various congenital anomalies. X-inactivation does not explain the variable phenotype. Males born to affected mothers may have omphalocele, hypoplastic kidneys, or other anomalies. Melnick-Needles syndrome may not always be lethal in males. There are similarities with other related disorders.", "NEURODEVELOPMENTAL DISORDER WITH HEARING LOSS, SEIZURES, AND BRAIN ABNORMALITIES": "Severe neurodevelopmental disorder with delayed psychomotor and intellectual development, microcephaly, seizures, abnormal EEGs, hypotonia/hypertonia/spasticity, nonambulatory/nonverbal, impaired vision/hearing, abnormal brain MRI, thrombocytopenia/immunodeficiency, dysmorphic facial features, elevated blood copper levels.", "KAGAMI-OGATA SYNDROME": "Phenotype characteristics of paternal uniparental disomy for chromosome 14 (UPD14(pat)) include skeletal abnormalities, joint contractures, dysmorphic facial features, developmental delay/mental retardation, narrow bell-shaped thorax, cranial and caudal bowing of ribs, flaring of iliac wings, predominantly axial skeleton involvement, inheritance of Robertsonian translocation or de novo paternal isochromosome, severe phenotype often associated with spontaneous miscarriage, hairy forehead, protruding philtrum, micrognathia, small thorax, abdominal wall defects, coat-hanger appearance of ribs, amelioration of thoracic deformity with age, mosaicism for supernumerary marker chromosome 14, kyphoscoliosis, hypoplasia of maxilla and mandible, broad nasal bridge, contractures of wrists, diastasis recti, muscle hypotonia, vertical skin creases under the chin, stippled epiphyses of humeri, respiratory infection leading to death, polyhydramnios, macrosomia, placentomegaly, respiratory distress, feeding difficulties, postnatal growth retardation, cardiac anomalies, omphalocele, inguinal hernias, hepatoblastoma, frontal bossing, depressed nasal bridge, anteverted nares, short neck, hypotonia, speech and/or motor delays, and normal to mildly impaired intellectual development.", "WILLIAMS-BEUREN SYNDROME": "Clinical features of this rare genetic disorder, known as Williams syndrome, include supravalvular aortic stenosis (SVAS), mental retardation, distinctive facial features, dental anomalies, peripheral pulmonary artery stenosis, infantile hypercalcemia, statural deficiency, characteristic dental malformation, and a hoarse voice. Other features may include renal abnormalities, cardiovascular disease, joint limitations, hypotonia, delayed growth, cataracts, stroke, and cognitive deficits. Patients with Williams syndrome often have musical and verbal abilities, but struggle with visual-motor integration and attention deficit disorder. They may also exhibit hypersensitivity to sounds and have urinary abnormalities.", "CORNELIA DE LANGE SYNDROME 1": "Thin vermilion border Bilateral single transverse palmar creases Global developmental delay Intrauterine growth retardation Anteverted nares Hypoplastic labia majora Curly eyelashes Posteriorly rotated ears Thick eyebrow Micromelia Cutis marmorata Micrognathia Hypoplastic nipples Downturned corners of mouth Small hand Brachycephaly Clinodactyly of the 5th finger Oligodactyly Depressed nasal bridge Generalized hirsutism Proximal placement of thumb Short stature Downturned corners of mouth Feeding difficulties in infancy Truncal obesity Conductive hearing impairment Asymmetric growth Long philtrum Toe syndactyly Micromelia Global developmental delay Short nose Hearing impairment Cryptorchidism Thin vermilion border Myopia Low posterior hairline Abnormally low-pitched voice Micrognathia Abnormality of speech or vocalization Short stature Widely spaced teeth Radioulnar synostosis Wide nasal bridge Low-set ears Long eyelashes Limited elbow extension Wide nasal bridge Intestinal malrotation Severe postnatal growth retardation Intellectual disability, severe Proximal placement of thumb Short 1st metacarpal Attention deficit hyperactivity disorder Microcephaly Failure to thrive Hypoplasia of penis Toe syndactyly Gastroesophageal reflux Thick eyebrow Premature birth Abnormal aggressive, impulsive or violent behavior Highly arched eyebrow obsolete Abnormality of the ulna Prenatal movement abnormality Atrial septal defect Abnormality of cardiovascular system morphology Synophrys Synophrys Intellectual disability Short foot Microcephaly Talipes Intellectual disability, severe Ptosis Blepharitis High palate Low-set ears Strabismus Sensorineural hearing impairment Seizure Increased nuchal translucency Thickened helices", "CORNELIA DE LANGE SYNDROME 2": "Thin vermilion border Bilateral single transverse palmar creases Global developmental delay Intrauterine growth retardation Anteverted nares Hypoplastic labia majora Curly eyelashes Posteriorly rotated ears Thick eyebrow Micromelia Cutis marmorata Micrognathia Hypoplastic nipples Downturned corners of mouth Small hand Brachycephaly Clinodactyly of the 5th finger Oligodactyly Depressed nasal bridge Generalized hirsutism Proximal placement of thumb Short stature Downturned corners of mouth Feeding difficulties in infancy Truncal obesity Conductive hearing impairment Asymmetric growth Long philtrum Toe syndactyly Micromelia Global developmental delay Short nose Hearing impairment Cryptorchidism Thin vermilion border Myopia Low posterior hairline Abnormally low-pitched voice Micrognathia Abnormality of speech or vocalization Short stature Widely spaced teeth Radioulnar synostosis Wide nasal bridge Low-set ears Long eyelashes Limited elbow extension Wide nasal bridge Intestinal malrotation Severe postnatal growth retardation Intellectual disability, severe Proximal placement of thumb Short 1st metacarpal Attention deficit hyperactivity disorder Microcephaly Failure to thrive Hypoplasia of penis Toe syndactyly Gastroesophageal reflux Thick eyebrow Premature birth Abnormal aggressive, impulsive or violent behavior Highly arched eyebrow obsolete Abnormality of the ulna Prenatal movement abnormality Atrial septal defect Abnormality of cardiovascular system morphology Synophrys Synophrys Intellectual disability Short foot Microcephaly Talipes Intellectual disability, severe Ptosis Blepharitis High palate Low-set ears Strabismus Sensorineural hearing impairment Seizure Increased nuchal translucency Thickened helices", "CORNELIA DE LANGE SYNDROME 4 WITH OR WITHOUT MIDLINE BRAIN DEFECTS": "Thin vermilion border Bilateral single transverse palmar creases Global developmental delay Intrauterine growth retardation Anteverted nares Hypoplastic labia majora Curly eyelashes Posteriorly rotated ears Thick eyebrow Micromelia Cutis marmorata Micrognathia Hypoplastic nipples Downturned corners of mouth Small hand Brachycephaly Clinodactyly of the 5th finger Oligodactyly Depressed nasal bridge Generalized hirsutism Proximal placement of thumb Short stature Downturned corners of mouth Feeding difficulties in infancy Truncal obesity Conductive hearing impairment Asymmetric growth Long philtrum Toe syndactyly Micromelia Global developmental delay Short nose Hearing impairment Cryptorchidism Thin vermilion border Myopia Low posterior hairline Abnormally low-pitched voice Micrognathia Abnormality of speech or vocalization Short stature Widely spaced teeth Radioulnar synostosis Wide nasal bridge Low-set ears Long eyelashes Limited elbow extension Wide nasal bridge Intestinal malrotation Severe postnatal growth retardation Intellectual disability, severe Proximal placement of thumb Short 1st metacarpal Attention deficit hyperactivity disorder Microcephaly Failure to thrive Hypoplasia of penis Toe syndactyly Gastroesophageal reflux Thick eyebrow Premature birth Abnormal aggressive, impulsive or violent behavior Highly arched eyebrow obsolete Abnormality of the ulna Prenatal movement abnormality Atrial septal defect Abnormality of cardiovascular system morphology Synophrys Synophrys Intellectual disability Short foot Microcephaly Talipes Intellectual disability, severe Ptosis Blepharitis High palate Low-set ears Strabismus Sensorineural hearing impairment Seizure Increased nuchal translucency Thickened helices", "CORNELIA DE LANGE SYNDROME 5": "Thin vermilion border Bilateral single transverse palmar creases Global developmental delay Intrauterine growth retardation Anteverted nares Hypoplastic labia majora Curly eyelashes Posteriorly rotated ears Thick eyebrow Micromelia Cutis marmorata Micrognathia Hypoplastic nipples Downturned corners of mouth Small hand Brachycephaly Clinodactyly of the 5th finger Oligodactyly Depressed nasal bridge Generalized hirsutism Proximal placement of thumb Short stature Downturned corners of mouth Feeding difficulties in infancy Truncal obesity Conductive hearing impairment Asymmetric growth Long philtrum Toe syndactyly Micromelia Global developmental delay Short nose Hearing impairment Cryptorchidism Thin vermilion border Myopia Low posterior hairline Abnormally low-pitched voice Micrognathia Abnormality of speech or vocalization Short stature Widely spaced teeth Radioulnar synostosis Wide nasal bridge Low-set ears Long eyelashes Limited elbow extension Wide nasal bridge Intestinal malrotation Severe postnatal growth retardation Intellectual disability, severe Proximal placement of thumb Short 1st metacarpal Attention deficit hyperactivity disorder Microcephaly Failure to thrive Hypoplasia of penis Toe syndactyly Gastroesophageal reflux Thick eyebrow Premature birth Abnormal aggressive, impulsive or violent behavior Highly arched eyebrow obsolete Abnormality of the ulna Prenatal movement abnormality Atrial septal defect Abnormality of cardiovascular system morphology Synophrys Synophrys Intellectual disability Short foot Microcephaly Talipes Intellectual disability, severe Ptosis Blepharitis High palate Low-set ears Strabismus Sensorineural hearing impairment Seizure Increased nuchal translucency Thickened helices", "KABUKI SYNDROME 1": "Clinical features of Kabuki syndrome include:\n1. Peculiar facial characteristics: eversion of lower lateral eyelid, arched eyebrows, depressed nasal tip, prominent ears.\n2. Skeletal anomalies: brachydactyly V, spinal deformity, cleft vertebrae.\n3. Dermatoglyphic abnormalities: increased digital ulnar loop, hypothenar loop patterns, absence of digital triradius c and/or d, fingertip pads.\n4. Mild to moderate mental retardation.\n5. Postnatal growth deficiency.\n6. Fetal finger pads.\n7. Congenital heart defects.\n8. Early breast development in some infant girls.\n9. Autosomal dominant inheritance with variable expressivity.\n10. Variable additional features: heart abnormalities, hair abnormalities, oral manifestations, hearing loss, behavior phenotype, gastrointestinal issues, immune deficiencies, ocular abnormalities, growth abnormalities.", "POIKILODERMA, HEREDITARY FIBROSING, WITH TENDON CONTRACTURES, MYOPATHY, AND PULMONARY FIBROSIS": "Clinical features of the rare genetic disorder include heat intolerance, facial skin lesions, Achilles tendon contractures, telangiectasia, mottled hyper- and hypopigmentation, papules, epidermal atrophy, fine scalp hair, thin eyebrows, limited hair on arms and legs, bilateral atrophy of hand muscles, limited finger extension, hypohidrosis, restrictive lung function, truncal obesity, scleroderma-like skin changes, elastic tissue degeneration, interstitial fibrosis of lungs, fibrosis of esophagus and lymph nodes, arterial degeneration, fatty infiltration of pancreas and skeletal muscle, poikiloderma, alopecia, muscle weakness, tendinous contractures, and heat intolerance.", "PIGV": "Rare genetic disorder characterized by severe mental retardation, seizures, and elevated alkaline phosphatase. Other features include neurologic abnormalities, delayed motor and speech development, hypoplastic terminal phalanges, hypoplastic nails, hypotonia, delayed myelinization in the brain, distinct facial features (hypertelorism, downturned corners of the mouth), and various congenital anomalies (anteriorly displaced anus, clefting of the palate, anovestibular fistula, ventricular septal defect). Patients may have intracellular inclusions in some tissues. The disorder is associated with hyperphosphatasia and is distinct from Coffin-Siris syndrome.", "XIA-GIBBS SYNDROME": "Rare genetic disorder: Xia-Gibbs syndrome\nPhenotype characteristics:\n- Impaired intellectual development\n- Failure to thrive\n- Hypotonia\n- Delayed psychomotor development\n- Absent or poor expressive language\n- Mild dysmorphic features (low-set or protuberant ears, flat nasal bridge, esotropia, hypertelorism, up- or downslanting palpebral fissures, micrognathia)\n- Obstructive sleep apnea\n- Laryngomalacia or tracheomalacia\n- Brain abnormalities (hypoplasia of the corpus callosum, simplified gyral pattern, delayed myelination, retrocerebellar cyst)\n- Developmental delay\n- Dysmorphisms\n- Growth or feeding issues\n- Cognitive delay\n- Ataxia\n- Autism\n- Brain abnormalities (corpus callosum abnormalities, subependymal cysts, hypomyelination)\n- Other features (omphalocele, left central macular dystrophy, clubfoot with pes cavus, sagittal craniosynostosis, cochlear nerve dysfunction, hypermobile joints)\n- Hypotonia\n- Developmental delay\n- Dysmorphic features (midface hypoplasia, hypertelorism, micrognathia, upslanting palpebral fissures)\n- Laryngomalacia\n- Brain abnormalities (frontal and temporal cortical atrophy, loss of posterior ventricular white matter)\n- Speech and motor developmental delay\n- Hypotonia (hypertonia in one patient)\n- Impaired intellectual development\n- Growth or feeding issues\n- Anatomic upper airway obstruction\n- Joint laxity\n- Scoliosis and lumbar lordosis in some patients\n- Structural brain abnormalities (corpus callosum abnormalities, cerebral atrophy, ventriculomegaly, diffuse cerebral atrophy, small pituitary)\n- Craniosynostosis\n- Broad clinical spectrum with multisystemic involvement\n- Bilateral coronal craniosynostosis\n- Seizures\n- Abnormal EEG findings\n- Brain abnormalities (cystic encephalomalacia, T2A and FLAIR enhancement, thin corpus callosum)\n- Microcephaly\n- Brachycephaly\n- Lack of speech\n- Hairy forehead\n- Thin upper lip\n- Strabismus\n- Almond-shaped eyes\n- Laryngomalacia", "BICRA": "Patients with this rare genetic disorder exhibit global developmental delay, impaired motor and intellectual development, speech and language delay, hypotonia, feeding difficulties, failure to thrive, autistic features, seizures, sensorineural hearing loss, dysmorphic facial features, microcephaly, macrocephaly, frontal bossing, bitemporal narrowing, high or low anterior hairline, arched eyebrows, synophrys, long eyelashes, epicanthal folds, small or slanted palpebral fissures, deep-set eyes, low-set ears, posteriorly rotated ears, prominent nasal bridge, bulbous or rounded nasal tip, low columella, thin upper lip, long or short philtrum, high-arched palate, micrognathia, square or pointed chin, scoliosis, joint laxity, fifth digit/nail hypoplasia (in some cases), constipation, gastroesophageal reflux, myopia, and hyperopia. The phenotype overlaps with Coffin-Siris syndrome and other SWI/SNF-related intellectual disability disorders, but has distinct features.", "HYPERPHOSPHATASIA WITH MENTAL RETARDATION SYNDROME 4": "Clinical features of HPMRS4 include severely delayed psychomotor development, hypotonia, inability to speak or walk independently, seizures, dysmorphic facial features (hypertelorism, upslanting palpebral fissures, broad nasal bridge, short nose, long philtrum, tented upper lip, full cheeks, large fleshy earlobes), postnatal microcephaly, cleft palate, thin corpus callosum, dilated lateral ventricles, increased serum alkaline phosphatase, bulbous nose, epicanthal folds, megalocornea, overlapping toes, abnormal dentition, hypoplastic cerebellum, communication between third ventricle and posterior fossa, brain atrophy, hearing loss, characteristic facies, abnormal teeth, megalocornea, congenital heart defects, impaired intellectual development, hypotonia, epilepsy, abnormal MRI findings, microretrognathia, wide anterior fontanel, left ear pit, pectus carinatum, hypoplastic nails, left inguinal hernia, patent foramen ovale, frontoparietal atrophy, bilateral enlargement of lateral ventricles, profound developmental delay, aspiration pneumonia, blue sclerae, hypertrophic gums, thin sparse hair, pectus excavatum, umbilical hernia, unilateral pes equinovarus, callosal dysgenesis, minor hippocampal structural anomaly, and elevated alkaline phosphatase levels.", "DDX3X": "Clinical features of the rare genetic disorder include impaired intellectual development, variable neurologic features (such as hypotonia, movement disorders, and microcephaly), behavioral problems (including autism spectrum disorder, hyperactivity, and aggression), epilepsy, joint hyperlaxity, skin pigmentary abnormalities, cleft lip and/or palate, hearing and visual impairment, precocious puberty, abnormal brain imaging findings, dysmorphic facial features, macrocephaly, progressive spasticity, dysarthria, spastic paraparesis, learning disabilities, brain MRI findings (such as white matter loss and ventriculomegaly), cardiac anomalies, ophthalmologic and hearing issues, central nervous system malformations, scoliosis, pilocytic astrocytoma, IUGR, hypotonia, feeding problems, sensorineural hearing loss, akinetic seizures, hand stereotypies, dystonia, cyclical vomiting syndrome, cutaneous mastocytosis, microcephaly, dolichocephaly, epicanthal folds, telecanthus, large ears, hypopigmented spots, joint hypermobility, and thin corpus callosum.", "Noonan syndrome": "Noonan syndrome is characterized by various clinical features including webbing of the neck, coarctation of the aorta, cryptorchidism, pterygium colli, deformed sternum, myocardiopathy, pulmonary stenosis, patent ductus arteriosus, elevated alkaline phosphatase levels, seizures, anomalous upper lateral incisors, lymphedema, posterior cervical hygroma, cutaneous lymphangioma, craniofacial anomalies, hypertrophic cardiomyopathy, short stature, headache, Arnold-Chiari malformation, ECG abnormalities, congenital heart defects, and motor performance impairments.", "PSMC3": "Early-onset and rapidly progressive deafness, early-onset cataract, severe developmental delay, severely impaired intellectual development, subcutaneous calcifications, peripheral neuropathy, positive otoacoustic emissions at birth, profound deafness confirmed by auditory brainstem responses. Cochlear implants were received, but language development was not achieved in two patients who received implants after the age of 2 years. Severe language delay in the third patient despite receiving implants at 22 months. Bilateral cataracts requiring lensectomies. Subcutaneous calcifications, polyneuropathy, and depigmented hair observed in some patients.", "KLIPPEL-FEIL SYNDROME 4, AUTOSOMAL RECESSIVE, WITH NEMALINE MYOPATHY AND FACIAL DYSMORPHISM": "Text 1: Alazami et al (2015)\n- Klippel-Feil syndrome with myopathy\n- Mild short stature, microcephaly, and distinctive facies\n- Motor delay, hypotonia, and muscle weakness\n- Dysmorphic features including short webbed neck, low posterior hairline, bilateral ptosis, and bulbous nose\n- Fusion of cervical spine, scoliosis, and acetabular dysplasia\n\nText 2: Brunet et al (2020)\n- Klippel-Feil syndrome type 4\n- Generalized muscular hypotonia\n- Cleft palate, microretrognathia, and clinodactyly\n- Low-set ears, high forehead, downslanting palpebral fissures, and long philtrum\n- Ulnar deviation of hands, camptomelic fingers, and lowly implanted thumbs\n- Small patent foramen ovale and ventricular septal defect\n- Feeding difficulties, obstructive bronchitis, and reduced neck movement\n- Facial weakness, bilateral ptosis, excessive body hair, thoracolumbar scoliosis, and progressive microcephaly\n\nText 3: Malfatti et al (2015)\n- Severe nemaline myopathy and fatal cardiomyopathy\n- Hypotonia, tendon contractures, and poor feeding\n- Dysmorphic features including enlarged skull, small palpebral fissures, high-arched palate, and low-set ears\n- Pectus excavatum, low implanted thumbs, and clinodactyly\n- Hypertrophic left cavities, interatrial communication, and pulmonary hypertension\n- Fiber size variability, atrophic fibers, and nemaline bodies in muscle biopsy\n- Cardiomyopathy variant-specific with truncated MYO18B protein detected\n\nNote: The summaries are within the 500-token limit.", "CHAMP1": "Rare genetic disorder: CHAMP1 gene mutation\n- Intellectual disability, severe speech impairment\n- Dysmorphic features: microcephaly, long face, open mouth, epicanthal folds, strabismus, upslanting palpebral fissures, short philtrum, tented upper lip, everted lower lip, high-arched palate, pointed chin, low-set ears\n- Additional features: hypotonia, feeding difficulties, delayed psychomotor development, hyperopia, decreased pain sensation, recurrent infections, ataxic gait, stereotypic movements, joint hypermobility\n- Brain imaging: normal or mild atrophy, delayed myelination, cerebellar cortical dysplasia\n- Behavioral abnormalities: autistic behavior, unmotivated laughter, aggressiveness\n- Ophthalmologic issues: hypermetropia, astigmatism, amblyopia, nystagmus\n- Associated conditions: seizures, failure to thrive, developmental delay, motor delay, gait abnormalities\n- Autism spectrum disorder traits, attention deficit-hyperactivity disorder, obsessive-compulsive disorder traits", "INTELLECTUAL DEVELOPMENTAL DISORDER WITH SPEECH DELAY, DYSMORPHIC FACIES, AND T-CELL ABNORMALITIES": "Neurodevelopmental disorder with delayed psychomotor development, intellectual disability, speech delay, autistic features, ADHD, anxiety, and behavioral abnormalities. Dysmorphic features include myopathic facies, thin eyebrows, small palpebral fissures, hypertelorism, epicanthal folds, prominent nose, long philtrum, thin upper lip, and small mouth. Some patients had spasticity, abnormal movements, and brain abnormalities. Other features include seizures, microcephaly, feeding difficulties, vision problems, dental anomalies, frequent infections, allergies, and asthma. Immunologic abnormalities observed in some patients. Decreased numbers of ILC2s.", "WHITE-SUTTON SYNDROME": "Rare genetic disorder: POGZ gene mutations. Clinical features include intellectual disability, global developmental delay, behavioral/psychiatric problems, seizures, abnormal ear, hearing impairment, hypotonia, visual abnormalities, speech/language delay, autistic features, dysmorphic features, obesity, feeding difficulties, short stature, gastrointestinal manifestations, visual and hearing abnormalities, seizures, congenital anomalies, impaired intellectual development, speech delay, hypotonia, seizures, abnormal head imaging, facial features, ophthalmologic problems, hearing loss, gastrointestinal involvement, and sleep disorders.", "CARDIOFACIOCUTANEOUS SYNDROME 2": "Clinical features of cardiofaciocutaneous syndrome (CFC) include hypotonia, hypertrophic obstructive cardiomyopathy, atrial septal defect, pulmonic stenosis, delayed development, short stature, high forehead with bitemporal constriction, bilateral ptosis, sparse eyebrows and eyelashes, short and broad-based nose with anteverted nostrils, low-set posteriorly rotated ears, and sparse, fine, curly hair. Peripheral sensorimotor axonal neuropathy and Charcot arthropathy of the feet may also occur. Germline KRAS mutations are associated with CFC and can be vertically transmitted. The phenotype of CFC overlaps with Noonan and Costello syndromes.", "NOONAN SYNDROME 3": "Noonan syndrome: severe phenotype, JMML-like myeloproliferative disorder, atrial and ventricular septal defects, valvular pulmonary stenosis, dysmorphic facial features, short stature, webbed neck, severe developmental delay, macrocephaly, sagittal suture synostosis, craniosynostosis, polyhydramnios, cystic hygroma, abnormal skull shape, frontal bossing, hypertelorism, low-set ears, short nose with anteverted nares, pterygium colli, right ventricular and septal hypertrophy, open foramen ovale, Chiari 1 malformation, closure of left lamboidal suture, reduced growth, epicanthic folds, ptosis, downslanting palpebral fissures, strabismus, hypoplastic nasal bridge, prominent philtrum, high palate, low-set and posteriorly rotated ears, mild pectus excavatum, dysplastic pulmonary valve, mild interventricular septum hypertrophy, mild cognitive deficits. Craniosynostosis not commonly recognized.", "INTELLECTUAL DEVELOPMENTAL DISORDER WITH SPEECH DELAY, AUTISM, AND DYSMORPHIC FACIES": "Rare genetic disorder associated with de novo heterozygous mutations in CNOT3 gene. Clinical features include delayed walking, hypotonia, delayed or absent speech, intellectual disability, learning difficulties, and autism. Dysmorphic features present but no consistent pattern. Some patients have seizures, brain imaging abnormalities, foot deformities, kyphosis, scoliosis, and skin pigmentation anomalies. In some cases, moyamoya disease with bilateral or unilateral angiopathy and ischemic stroke.", "MSL3": "Rare genetic disorder: Neurodevelopmental disorder associated with point mutations in the MSL3 gene. Common features: Hypotonia, feeding difficulties, global delay in cognitive skills, motor milestones, and speech. Behavioral abnormalities, progressive spasticity, skeletal abnormalities, dysmorphic facial features. Brain imaging normal in most. Seizures, hearing loss, and retinal abnormalities observed in few. Developmental delay in all patients with varying severity. Autism spectrum disorder in 50%. Hypotonia, movement disorders, and seizures seen. MRI shows cerebellar vermis hypoplasia. Gastrointestinal, genitourinary, hearing, macrocephaly, and vision problems. Clinical management recommendations include referrals and regular follow-up.", "BLOOM SYNDROME": "Bloom syndrome is a rare genetic disorder primarily affecting Ashkenazi Jews. Clinical features include telangiectasia, stunted growth, sensitivity to sunlight, and increased risk of malignancies, particularly hematologic malignancies and carcinomas. Other characteristics include delayed puberty in females, early menopause, and infertility in males. Diabetes mellitus and cardiomyopathy may also occur. The disorder may be underdiagnosed in populations with different skin pigmentation. Consanguinity is common among affected individuals. Preterm labor and small pelvis size may be observed in pregnancies of women with Bloom syndrome.", "RECQL3": "Bloom syndrome is a rare genetic disorder primarily affecting Ashkenazi Jews. Clinical features include telangiectasia, stunted growth, sensitivity to sunlight, and increased risk of malignancies, particularly hematologic malignancies and carcinomas. Other characteristics include delayed puberty in females, early menopause, and infertility in males. Diabetes mellitus and cardiomyopathy may also occur. The disorder may be underdiagnosed in populations with different skin pigmentation. Consanguinity is common among affected individuals. Preterm labor and small pelvis size may be observed in pregnancies of women with Bloom syndrome.", "COCKAYNE SYNDROME A": "Clinical features of this rare genetic disorder, possibly Cockayne syndrome, include dwarfism, microcephaly, severe mental retardation, 'pepper-and-salt' chorioretinitis, intracranial calcification, normal pressure hydrocephalus, hypertension, renal disease, decreased thyroid hormone, leukodystrophy, ocular abnormalities (strabismus, cataracts, nystagmus), absence of cancer and infectious complications, growth failure, cold extremities, abnormal brain imaging (calcifications, white matter changes), weakness, hearing loss, clinical photosensitivity, tremor, joint contractures, abnormal liver function tests, abnormal bowel movements, and typical facial features. Early onset cataracts are associated with younger age at death.", "POIKILODERMA WITH NEUTROPENIA": "Clinical features of the rare genetic disorder include:\n- Onset of papular erythematous rash on limbs during first year of life\n- Rash spreads centripetally and resolves with hypo- and hyperpigmentation, telangiectases\n- Pachyonychia present, alopecia and leukoplakia absent\n- Recurrent pneumonias leading to reactive airway disease and chronic cough\n- Neutropenia, possibly cyclical\n- Autosomal recessive inheritance, common in Navajo population\n- Similarities to Rothmund-Thomson syndrome, but with different skin lesion distribution and absence of alopecia and skeletal manifestations\n- Other features may include plantar keratoderma, nail dystrophy, facial dysmorphism, short stature, and hypogonadism\n- Increased risk of respiratory infections, bronchopulmonary infections, and bronchocentric granulomatous pneumonia\n- No reported cases of skin cancer or myelodysplastic disorders\n- Some patients may have interstitial lung disease, bronchiectasis, and noncaseating granulomas\n- Mutations in the USB1 gene have been identified in some cases\n- Laboratory findings may include leukopenia, neutropenia, elevated ferritin levels, and abnormal bone marrow evaluation.", "FAM111B": "Clinical features of the rare genetic disorder include heat intolerance, facial skin lesions, Achilles tendon contractures, telangiectasia, mottled hyper- and hypopigmentation, papules, epidermal atrophy, fine scalp hair, thin eyebrows, limited hair on arms and legs, bilateral atrophy of hand muscles, limited finger extension, hypohidrosis, restrictive lung function, truncal obesity, scleroderma-like skin changes, elastic tissue degeneration, interstitial fibrosis of lungs, fibrosis of esophagus and lymph nodes, arterial degeneration, fatty infiltration of pancreas and skeletal muscle, poikiloderma, alopecia, muscle weakness, tendinous contractures, and heat intolerance.", "ROTHMUND-THOMSON SYNDROME, TYPE 2": "Clinical features of the rare genetic disorder, Rothmund-Thomson syndrome (RTS), include poikiloderma, lenticular opacities, atrophy, pigmentation, telangiectasia, juvenile cataract, saddle nose, congenital bone defects, disturbances of hair growth, hypogonadism, severe skeletal dysplasia, joint abnormalities, kyphoscoliosis, hypermobility, cutaneous ulcers, mesodermal dysgenesis of the iris, hypodontia, soft tissue contractures, proportionate short stature, anemia, and osteogenic sarcoma. There are two forms of RTS: type 1, characterized by poikiloderma without osteosarcoma, and type 2, characterized by poikiloderma with an increased risk of osteosarcoma and deleterious mutations in the RECQL4 gene. Clinical variability exists, with some patients exhibiting additional features such as bilateral radial aplasia, inflammatory gut disorders, cleft palate, micrognathia, anal atresia, patellar aplasia/hypoplasia, and sensorineural deafness.", "INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 72": "Patients with a mutation in the MRT72 gene exhibit a similar intellectual developmental disorder. They have globally impaired development, delayed walking and fine motor skills, poor speech acquisition, and cognitive deficits. They also have poor overall growth, microcephaly, and dysmorphic facial features. Brain imaging shows no abnormalities. Hearing impairment, visual defects, and seizures are not present. In another study, brothers with the same phenotype had normal early development but experienced learning difficulties. They had microcephaly, strabismus, narrow nasal base, broad nasal ridge, long philtrum, thin upper lip, and large ears. IQs indicated severe impairment, and both had aggressive behavior.", "VICI SYNDROME": "Clinical features of Vici syndrome include:\n- Agenesis of the corpus callosum\n- Cutaneous hypopigmentation\n- Bilateral cataract\n- Cleft lip and palate\n- Combined immunodeficiency\n- Severe psychomotor retardation\n- Seizures\n- Recurrent severe respiratory infections\n- Chronic mucocutaneous candidiasis\n- Cardiomyopathy\n- Postnatal growth retardation\n- Microcephaly\n- Profound developmental delay\n- Hypotonia\n- Nystagmus\n- Sensorineural hearing loss\n- Skeletal muscle abnormalities\n- Coarse facial features (in older children)\n- Retinal hypopigmentation\n- Cleft palate\n- Failure to thrive\n- Increased susceptibility to infections\n- Progressive cardiac failure\n- Variable brain abnormalities (e.g., cerebellar and pontine hypoplasia, ventricular dilatation)\n- Variable dysmorphic features (e.g., depressed nasal bridge, micrognathia)\n- Variable ophthalmic abnormalities (e.g., optic neuropathy, macular atrophy)\n- Autosomal recessive inheritance", "SAUL-WILSON SYNDROME": "Clinical features of the rare genetic disorder include: open bulging fontanels, calcaneovalgus deformity, short stature, microcephaly, distinctive facial features (sharp narrow face, frontal bossing, metopic depression), blue sclerae, bilateral cataracts, opalescent teeth, pectus carinatum, upper lumbar lordosis, short hands with blunted fingers, bowed legs, delayed growth, delayed speech and motor development, wormian bones, widened clavicles, dysplastic L-1 vertebra, nonunion or pseudoarthrosis of the left tibia and fibula, distal phalangeal tufting, and normal fibroblast enzymes and sweat chloride.", "MICROCEPHALIC OSTEODYSPLASTIC PRIMORDIAL DWARFISM, TYPE II": "Clinical features of this rare genetic disorder include intrauterine and postnatal dwarfism, microcephaly, facial features resembling Seckel syndrome, disproportionate shortness of forearms and legs, brachymesophalangy, brachymetacarpy, V-shaped flare of distal femoral metaphyses, triangular shape of distal femoral epiphyses, high and narrow pelvis, proximal femoral epiphysiolysis, coxa vara, and delayed bone age. Other features may include intellectual disability, delayed myelination, hypopigmentation, dental abnormalities, and variable skeletal anomalies. Autosomal recessive inheritance is observed in some cases.", "NOONAN SYNDROME-LIKE DISORDER WITH LOOSE ANAGEN HAIR 1": "Clinical features of the rare genetic disorder include:\n- Short stature\n- Facial phenotype with macrocephaly, high forehead, hypertelorism, palpebral ptosis, and low-set and posteriorly rotated ears\n- Short neck with redundant skin\n- Enlarged cerebrospinal fluid spaces\n- Severe growth hormone deficiency\n- Mild psychomotor delay with attention deficit/hyperactivity disorder\n- Mild dilatation of the pulmonary root\n- Ectodermal abnormalities with darkly pigmented and hairless skin\n- Loose anagen hair syndrome with easily pluckable, sparse, thin, slow-growing, and silver-blond hair\n- Distinctive hyperactive behavior\n- Cognitive deficits\n- Darkly pigmented skin with eczema or ichthyosis\n- Cardiac anomalies, including mitral valve and septal defects\n- Hypernasal voice\n- Skin hyperpigmentation\n- Sparse light-colored hair that is slow-growing and unruly in texture\n- Increased fine wrinkles\n- Ligamentous laxity\n- Developmental delay\n- Structural cardiac anomalies\n- Hypotonia and macrocephaly\n- Polyhydramnios, high birth weight, and/or feeding tube requirement in some cases\n- Distinctive brain abnormalities, including relative megalencephaly and enlarged subarachnoid spaces\n- Cerebellar tonsillar ectopia\n- Prenatal diagnosis of cystic hygroma, hypertrophic cardiomyopathy, and absence of ductus venosus\n- Skeletal anomalies, including pectus carinatum and pectus excavatum\n- Clinical variability with features overlapping Noonan and CFC syndromes\n- Mutation in the SHOC2 gene\n- Optic nerve hypoplasia, nystagmus, poor hair growth, speech delay, and hyperactive behavior in some cases\n- Intellectual disability, high-arched palate, and clubbed nails in some cases.", "INTELLECTUAL DEVELOPMENTAL DISORDER WITH DYSMORPHIC FACIES AND BEHAVIORAL ABNORMALITIES": "Rare genetic disorder: \n- Syndromic intellectual developmental disorder \n- Delayed psychomotor development \n- Intellectual disability (ranging from mild to severe) \n- Delayed speech, some nonverbal \n- Mildly delayed walking \n- Seizures (in some patients) \n- Short stature \n- Strabismus, hypermetropia \n- Hypotonia \n- Sleeping difficulties \n- Distal mild skeletal anomalies \n- Behavioral abnormalities \n- Dysmorphic features \n- Small head circumference \n- Downslanting palpebral fissures \n- Hypertelorism \n- Low-set ears \n- Long philtrum \n- Narrow mouth \n- Everted lower lip \n- Long face \n- Enlarged ventricles (in some patients) \n- Obesity (in some patients) \n- Gastrointestinal problems \n- Vision problems", "KBG SYNDROME": "Clinical features of KBG syndrome include short stature, characteristic facies (telecanthus, wide eyebrows, brachycephaly), macrodontia, mental retardation, skeletal anomalies (abnormal vertebrae, short metacarpals, short femoral necks), male-to-male transmission, hypoplasia of cerebellar vermis, cystic dysplasia of the kidney, megalocornea, ventricular septal defect, chronic constipation, recurrent respiratory tract infections, delayed bone maturation, hypertelorism, developmental delay, triangular face, low anterior and posterior hairlines, bushy eyebrows, large prominent ears, long philtrum, anteverted nostrils, wide upper central incisors, clinodactyly, accessory cervical ribs, thoracic kyphosis, undescended testes, EEG anomalies, mixed hearing loss, palatal anomalies, behavioral issues, cryptorchidism, posterior fossa malformations, eye defects, congenital heart defects, atypical facies, hand anomalies, cognitive deficit, learning difficulties, attention deficit hyperactivity disorder, feeding difficulties, velopharyngeal insufficiency, epilepsy, hearing loss, hypertrichosis, juvenile idiopathic arthritis, and microcephaly.", "MENTAL RETARDATION, AUTOSOMAL DOMINANT 7": "Phenotype characteristics of the rare genetic disorder described in the texts include primary microcephaly, severe mental retardation, absence of speech, anxious autistic behavior, dysmorphic features (such as bitemporal narrowing, deep-set eyes, large simple ears, and a pointed nasal tip), failure to thrive as an infant, abnormal movements, hypoactivity, febrile seizures, mildly atrophic brain without structural abnormalities on MRI, eczema, hypoplasia of breasts, hallux valgus of feet, irregular implant of the toes, thick lower lip, mild hypotelorism, hypoplastic earlobes, history of intrauterine growth retardation and feeding difficulties, seizures of multiple types, severe speech delay, diffuse cortical atrophy on MRI, and hand stereotypies.", "CARDIAC, FACIAL, AND DIGITAL ANOMALIES WITH DEVELOPMENTAL DELAY": "Patients with this rare genetic disorder exhibit a range of clinical features. These include abnormal prenatal ultrasound findings, respiratory distress, poor feeding, hypotonia, jaundice, delayed motor and speech development, cardiac defects (such as pulmonary stenosis and patent ductus arteriosus), dysmorphic facial features (such as hairline abnormalities and low-set ears), wide-spaced nipples, umbilical hernia, distal anomalies of the hands and feet, seizures, tethered cord, hearing loss, cortical blindness, optic atrophy, and brain abnormalities.", "AU-KLINE SYNDROME": "Clinical features of the rare genetic disorder, known as Okamoto syndrome or Au-Kline syndrome (AUKS), include congenital hydronephrosis, severe mental retardation, growth failure, generalized floppiness, and cleft palate. Facial characteristics consist of midface hypoplasia, hypertrichosis, long eyelashes, prominent eyes, epicanthus, low-set ears, long ear lobe, flat nasal bridge, short upturned nose, long philtrum, and webbed neck. Other common features include cardiac anomalies, developmental delay, hypotonia, and skeletal abnormalities. Additional findings may include splenomegaly, anal stenosis, intestinal malrotation, and brain abnormalities. A mutation in the HNRNPK gene has been identified in some patients. AUKS shares similarities with Kabuki syndrome but has distinct features such as ridged metopic sutures, open mouths, and high pain tolerance. Prenatal presentation may include increased nuchal translucency and hydronephrosis. Patients often have missing teeth, malocclusion, and craniosynostosis. Congenital heart defects, genitourinary anomalies, and gastrointestinal malformations are common. Global developmental delay, intellectual disability, and hypotonia are universal. Neurologic features, musculoskeletal involvement, and oral abnormalities are also observed.", "CONGENITAL HEART DEFECTS, MULTIPLE TYPES, 2": "Text 5: TAB2 mutation in 2 patients with congenital heart defects. Woman had left ventricular outflow tract obstruction, subaortic stenosis, aortic regurgitation, and atrial fibrillation. Man had bicuspid aortic valve and aortic dilation.\n\nText 6: 3-generation family with congenital heart defects. Proband had tetralogy of Fallot, pulmonary atresia, ventricular septal defect, and atrial septal defect. Mitral and tricuspid valves prolapsed. Mother had bicuspid aortic valve and ventricular septal defect. Grandmother had mitral regurgitation and prolapsed tricuspid valve.\n\nText 1: 12-year-old boy with pulmonary valve stenosis, aortic root dilatation, atrial and ventricular septal defects, and patent ductus arteriosus. Valves appeared thickened, mitral valve prolapse, aortic regurgitation. Other features included hypotonia, facial dysmorphism, myopia, pale skin, and joint hypermobility.\n\nText 4: Sister, brother, and brother's daughter with congenital heart defects and collagen tissue disorder features. Polyvalvular heart disease, joint hypermobility, hyperextensible skin, short limbs, hearing impairment, and facial dysmorphism. Patient 1 had atrial septal aneurysm, patient 2 had myocardial noncompaction and bicuspid aortic valve, patient 3 had aortic root dilatation. Dilated cardiomyopathy and arrhythmias in both sibs. Patient 3 died suddenly at age 60.\n\nText 2: Large Chinese family with congenital heart disease. Valvular defects, tachypnea, shortness of breath, and fatigue. Proband had mild aortic stenosis, mitral, tricuspid, and aortic valve regurgitation. Atrial septal aneurysms in 3 affected sisters. Other abnormalities in sisters and nephew. Mother died from sudden cardiac arrhythmia. Proband had daughter with biventricular dilatation who died suddenly at age 2.\n\nNo connective tissue abnormalities in this family.", "ROBIN SEQUENCE WITH CLEFT MANDIBLE AND LIMB ANOMALIES": "Clinical features of the rare genetic disorder, Richieri-Costa-Pereira syndrome, include short stature, Robin sequence, cleft mandible, limb defects, low set and prominent ears, hypoplastic thumbs, clubfoot, and laryngeal anomalies. Females have normal intellect, while affected males may be stillborn or die within a week of birth. Other features include absence of lower incisors, voice disorder, and various skeletal abnormalities. The syndrome is predominantly found in Brazilian families, suggesting a founder effect. The severity of the syndrome can vary, with some cases being more severe than others.", "MICROCEPHALY, EPILEPSY, AND DIABETES SYNDROME 1": "Rare genetic disorder: Microcephaly, developmental delay, hypotonia, seizures, obesity, diabetes mellitus, presumed hypogonadism. Simplified gyral pattern on brain MRI, hypsarrhythmia on EEG. Reduced neurons, hypomyelination, apoptosis in cortex. Few insulin-positive beta cells in pancreas. Dysmorphic features: short forehead, bitemporal narrowing, anteverted nares, puffy cheeks, deep philtrum, tented upper lip, narrow palate, gingival hypertrophy. Skeletal anomalies, liver enzyme abnormalities, microalbuminuria. Phenotypic overlap with Wolcott-Rallison syndrome. Coarse facies, retractile testes, cortical blindness, lack of social smiling, hypertrichosis, tapered fingers. Intractable seizures, well-controlled diabetes.", "O'DONNELL-LURIA-RODAN SYNDROME": "Rare genetic disorder: Neurodevelopmental disorder associated with heterozygous protein-truncating variants in KMT2E gene. Clinical features include global developmental delay, hypotonia, speech difficulties, autism, ADHD, behavioral concerns, macrocephaly, seizures, epilepsy, gastrointestinal symptoms, dysmorphic features, cardiac defects, jaundice, kyphosis, tapering fingers, cryptorchidism. Missense mutations associated with more severe phenotype, including epilepsy and severe developmental delay. Deletions of chromosome 7q22 also observed. Male predominance, with affected females more likely to have epilepsy and affected males more likely to have autism.", "NEURODEVELOPMENTAL DISORDER WITH DYSMORPHIC FACIES, SLEEP DISTURBANCE, AND BRAIN ABNORMALITIES": "Patients with a rare genetic disorder caused by mutations in the KAT5 gene exhibit severe global developmental delay, impaired intellectual development, poor or absent speech, behavioral abnormalities, and sleep disturbances. They also have a range of craniofacial features such as a small head, round face, almond-shaped eyes, and low-set ears. Other characteristics include genitourinary anomalies, hearing loss, seizures, and variable brain abnormalities.", "INTELLECTUAL DEVELOPMENTAL DISORDER WITH IMPAIRED LANGUAGE AND DYSMORPHIC FACIES": "Patients with this rare genetic disorder exhibit impaired intellectual development, speech delay, and variable additional findings. They may experience feeding difficulties, delayed walking, unsteady gait, poor speech, and learning disabilities. Other features include hypotonia, tapering fingers, foot deformities, and dysmorphic facial features. Cardiac anomalies, renal abnormalities, and genital abnormalities may also be present. Less common features include hip dysplasia, eczema, inguinal hernia, and supernumerary nipple. Brain imaging may show normal findings or hypoplastic corpus callosum and delayed myelination. Seizures are not typically observed.", "3MC SYNDROME 1": "Clinical features of Michels syndrome (also known as 3MC syndrome) include blepharophimosis, blepharoptosis, epicanthus inversus, cleft lip/palate, skeletal abnormalities, craniosynostosis, telecanthus, hearing loss, and developmental defects of the eye. Other characteristics may include spina bifida occulta, cranial asymmetry, abnormality of the occipital bone, radioulnar synostosis, short fifth finger, low-set ears, large anterior fontanel, accessory nipples, tuberous angioma, supraumbilical depression, small hands with bilateral short fifth fingers, broad feet, and severe axial hypotonia. Growth hormone deficiency and secondary hypogonadism may also be present. The disorder is believed to be a single recessive spectrum encompassing Michels, Malpuech, Carnevale, and OSA syndromes.", "INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 62": "Patients with MRD62 exhibit mildly to moderately impaired intellectual development and motor delay. Language delay, nonspecific dysmorphic facial features, and visual impairment are also common. Some patients may have behavioral abnormalities. Early development is typically normal or mildly delayed, with normal acquisition of walking. Intellectual development ranges from mildly to moderately impaired, with some patients attending special schools. Language abilities vary, with some patients able to read and write while others have severe language impairments. Seizures may develop in some patients, along with autism spectrum disorder. Brain imaging may show mild cerebellar vermis or subcortical atrophy. Marfanoid features, such as highly arched palate, long face, long thin fingers, pectus or foot deformities, and mild scoliosis, may be present. Joint hyperlaxity, strabismus, nystagmus, pyramidal signs, motor clumsiness, and umbilical hernia are also observed in some patients.", "DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 87": "Text 1: Developmental delay, seizures, hypotonia, joint laxity, scoliosis, pica, hand-flapping, dysmorphic facial features.\nText 2: Developmental delay, epileptic spasms, tonic seizures, hypsarrhythmia, brain atrophy, white matter abnormalities, elevated protein in CSF.\nText 3: Developmental delay, infantile spasms, hypotonia, small head circumference, hypertelorism, prominent nose, high-arched palate, brain abnormalities.\nText 4: Developmental delay, hypotonia, epilepsy, autism, abnormal brain imaging, dysmorphic features, eye abnormalities.", "AUTISM, SUSCEPTIBILITY TO, 18": "Clinical features of the rare genetic disorder associated with CHD8 gene mutations include: autism spectrum disorder (ASD), impaired intellectual development, macrocephaly, supraorbital ridge, downslanting palpebral fissures, tall stature, attention problems, anxiety problems, seizures, regression, gastrointestinal problems (especially constipation), sleep problems, broad nasal bridge, long philtrum, cupid bow mouth, posteriorly rotated ears, hypotonia, clumsiness, speech delay/regression, motor coordination problems, ventriculomegaly/delayed myelination (brain abnormalities), sleep abnormalities, and gastrointestinal issues (including constipation).", "CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IIA": "Clinical features of the rare genetic disorder include loose redundant folds of skin, slow skin elasticity, widely persistent fontanels, oxycephaly, hip dislocation, and skeletal abnormalities. The disorder is more common in females and may be lethal to male fetuses. Other features include intrauterine growth retardation, congenital dislocation of the hip, developmental delay, neurologic findings, dysmorphic facial features, feeding problems, and abnormal glycosylation. The disorder is also associated with mental retardation, seizures, myopia, and connective tissue problems. Some cases may be misdiagnosed as Costello syndrome or wrinkly skin syndrome.", "DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 23": "Clinical features of this rare genetic disorder include developmental and epileptic encephalopathy, intractable seizures starting between 2 and 6 months of age, delayed psychomotor development, cortical visual impairment or blindness, poor or lack of speech, difficulties in activities of daily living, and dysmorphic features such as low anterior hairline, periorbital fullness, telecanthus, broad nasal bridge, and anteverted nares. Other features may include bitemporal narrowing, thick and duplicated eyebrows, synophrys, long eyelashes, enophthalmia, large prominent nasal root with bulbous tip, short philtrum, full lips, and abnormal ears. Brain imaging may show abnormalities in the pontobulbar sulcus, pontine hypoplasia, T2-weighted white matter abnormalities with occipital atrophy, and a thin corpus callosum.", "LUSCAN-LUMISH SYNDROME": "Clinical features of Luscan-Lumish syndrome include postnatal overgrowth, macrocephaly, obesity, speech delay, advanced carpal ossification, long and large hands and feet, facial features such as prominent forehead, downward slanting palpebral fissures, long nose, malar hypoplasia, and prominent mandible. Behavioral difficulties include attention deficit, temper tantrums, aggressiveness, shyness, and low sociability. Other features include ventricular dilatation, nodular and punctiform hypersignals in the brain, autism spectrum disorder, developmental delay, intellectual disability, behavioral compulsions, seizures, Chiari I malformation, hydrocephalus, syringomyelia, short stature, failure to thrive, motor delays, undescended testes, dysmorphic features, delayed bone age, soft elastic skin, hyperlaxity of joints, asymmetric face, high pain threshold, truncal obesity, joint hypermobility, hirsutism, and nevi.", "MENTAL RETARDATION, AUTOSOMAL RECESSIVE 58": "In both families described by Najmabadi et al (2011), members had nonsyndromic impaired intellectual development. One family had mild intellectual disability, while the other had severe intellectual disability. Cohen et al (2015) reported two adult brothers with MRT58 who exhibited global developmental delay, poor head control, progressive spasticity leading to loss of walking ability, no meaningful language, behavioral problems, and neurological abnormalities. Kojic et al (2021) described six patients with MRT58, including severely impaired intellectual development, autism spectrum disorder, developmental delay, seizures, dystonia, hypotonia, spasticity, ophthalmologic abnormalities, cardiac abnormalities, and brain MRI findings such as brain atrophy and loss of white matter.", "SPATA5": "Severe neurodevelopmental disorder with delayed psychomotor and intellectual development, microcephaly, seizures, abnormal EEGs, hypotonia/hypertonia/spasticity, nonambulatory/nonverbal, impaired vision/hearing, abnormal brain MRI, thrombocytopenia/immunodeficiency, dysmorphic facial features, elevated blood copper levels.", "MYASTHENIC SYNDROME, CONGENITAL, 22": "Clinical features of the rare genetic disorder CMS22 include severe neonatal hypotonia, eyelid ptosis, tented upper lip, feeding difficulties, high-arched palates, narrow bitemporal diameter, nasal dysarthria, waddling gait, growth hormone deficiency, facial weakness, paretic neck flexion, hypergonadotropic hypogonadism, fluctuating weakness, and cognitive impairment ranging from mild intellectual disability to normal intelligence. Ptosis is a distinguishing feature from Prader-Willi syndrome.", "SMITH-KINGSMORE SYNDROME": "Text 6: Megalencephaly, intractable seizures, macrocephaly, poor feeding, hypoglycemia, thrombocytopenia, hypotonia, callosal dysgenesis, dysmorphic features, narrow thorax, umbilical hernia, rhizomelic limb shortening, short proximal phalanges, pneumonia.\nText 1: Intellectual disability, macrocephaly, seizures, umbilical hernia, cafe-au-lait lesions, craniofacial features, ventricular system prominence, hypogenesis of corpus callosum, white matter loss, small mesencephalon, pons, and medulla.\nText 5: Progressive macrocephaly, delayed psychomotor development, intellectual disability, autistic features, hypotonia, dysmorphic features, iris coloboma, cryptorchidism, asthma, food allergies.\nText 4: Progressive macrocephaly, delayed psychomotor development, learning disabilities, dysmorphic features, cystic kidneys, intestinal polyps.\nText 3: Epilepsy, delayed development, cognitive impairment, intellectual disability, autistic features, macrocephaly, dysmorphic features, enlarged ventricles, thin corpus callosum, near-normal cognitive development.", "INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC, 35": "Text 1: Mental retardation, dysmorphic facial features, microcephaly, seizures, hypotonia, growth retardation, genitourinary abnormalities, cardiac septal defects, hearing loss, tapered fingers, camptodactyly, toe syndactyly, recurrent infections.\n\nText 2: MRXS35, early delivery, delayed psychomotor development, hypotonia, microcephaly, dysmorphic features, febrile seizures, myopia, ataxia/cerebellar syndrome, cryptorchidism, small testes.\n\nText 3: MRXS35, intrauterine growth retardation, hypotonia, delayed psychomotor development, dysmorphic features, spondyloepiphyseal dysplasia, scoliosis, osteoporosis, cerebellar hypoplasia, retinitis pigmentosa, inguinal hernia, renal tubulopathy, central hypothyroidism, hypermetropia, cryptogenic focal epilepsy.", "NEURODEVELOPMENTAL DISORDER WITH NEONATAL RESPIRATORY INSUFFICIENCY, HYPOTONIA, AND FEEDING DIFFICULTIES": "Rare genetic disorder characterized by:\n- Neonatal hypotonia\n- Severely delayed psychomotor development\n- Early-onset feeding difficulties\n- Significant respiratory insufficiency\n- Early-onset seizures (often myoclonic)\n- Abnormal EEG pattern\n- Dysmorphic facial features (variable)\n- Myopathic facies (open mouth, high-arched palate)\n- Nystagmus and strabismus\n- Hypomyelination or delayed myelination on brain imaging\n- Nonverbal and nonambulatory\n- Phenotypic overlap with chromosome 5q31.3 microdeletion syndrome\n- Endocrine abnormalities may be present\n- Global developmental delay\n- Limited vocabulary or nonverbal communication\n- Variable visual impairment\n- Mild dysmorphic features\n- Cerebellar vermis hypoplasia, cystic dilatation, mega cisterna magna, and hypomyelination on brain imaging\n- Reduced expression of GLUT1 in patient red blood cells\n- Left ventricular hypertrophic myocardiopathy\n- Hiccups in utero\n- Neonatal problems (hypotonia, feeding difficulties, respiratory insufficiency)\n- Hypersomnolence, hypothermia, exaggerated startle response\n- Severely delayed walking or inability to walk\n- Moderate to severely impaired intellectual development\n- Abnormal movement (spasticity, stereotypic hand movements, dystonia or chorea-like movements)\n- Peripheral neuropathy in some cases\n- Onset of seizures in the first decade\n- Abnormal findings on brain imaging (delayed myelination, white matter abnormalities, parenchymal atrophy)\n- Visual problems or eye anomalies (strabismus, nystagmus, cortical visual impairment)\n- Scoliosis, progressive hip dysplasia, joint hyperlaxity\n- Dysmorphic facial features (hypotonic facies, high anterior hairline, full cheeks, almond-shaped palpebral fissures, well-defined philtrum, retrognathia)\n- Systemic involvement (cardiac defects, constipation, gastroesophageal reflux, cryptorchidism, short stature, small hands and feet, endocrine abnormalities)\n- Hypotonia, severe global developmental delay, inability to walk or speak\n- Poor visual fixation and tracking, feeding difficulties requiring tube feeding\n- Decreased cerebral volume and delayed myelination on brain imaging\n- Distinctive facial features (tented upper lip vermilion, long philtrum, strabismus, depressed nasal bridge with anteverted nares)\n- Primary amenorrhea in some cases.", "BARAITSER-WINTER SYNDROME 1": "Clinical features of the rare genetic disorder include iris coloboma, bilateral ptosis, hypertelorism, broad nasal bridge, prominent epicanthal folds, short stature, mental retardation, craniofacial dysmorphism, edema, narrowing of the frontal part of the skull, arched eyebrows, trigonocephaly, hypertelorism with a broad root and bridge of the nose, large mouth with a fine upper lip and everted lower lip, prominent upper central incisors, posteriorly rotated hypoplastic ears, high-arched palate, short and broad neck, widely spaced hypoplastic inverted nipples, neonatal edema followed by significant weight loss, complex epilepsy, pachygyria, limited extension at knees and elbows, normal metabolic investigations and karyotypes, multiple craniofacial and skeletal dysmorphic features, bilateral frontal pachygyria, brachycephaly, wide forehead, hypertelorism, wide palpebral fissures with multiple eyelid colobomas, broad nasal root, long philtrum, macrostomia, prominent lips, high-arched palate, midline alveolar cleft, small and grooved chin, ear anomalies, structural anomaly of the corpus callosum, brachyacrocephaly, absent nasal tip, wide columella, carp-like mouth, submucous cleft of the soft palate, Dandy-Walker anomaly, gray matter heterotopia, brachycephaly, wide forehead, macroblepharon with eyelid colobomas, ectropion, depressed nasal tip, macrostomia, small and grooved chin, ear anomalies, structural anomaly of the corpus callosum, dilatation of the fourth ventricle, urogenital sinus, dysmorphic facial features, facial edema, temporal flattening, webbed neck, hypoplastic thorax with inverted nipples, limited extension of elbows and knees, epilepsy, severe mental retardation, diffuse pachygyria, short stature, microcephaly, intellectual disability, seizures, hearing loss, colobomata of the iris or retina, anterior-to-posterior gradient lissencephaly, reduction of shoulder girdle muscle bulk, progressive joint stiffness, muscular involvement, congenital arthrogryposis, cleft lip and palate, hallux duplex, congenital heart defects, renal tract anomalies, dysmorphic facial features with hypertelorism, broad nose, congenital nonmyopathic ptosis, ridged metopic sutures, sensorineural deafness, microcephaly, pachygyria, lissencephaly, reduction of shoulder girdle muscle bulk, progressive joint stiffness, intellectual disability, epilepsy, acute lymphocytic leukemia, cutaneous lymphoma, pleiotropic developmental disorder, feeding difficulties, growth retardation, microcephaly, intellectual disability, speech and motor delay, behavioral abnormalities, dystonia, pectus deformities, tracheoesophageal fistula, esophageal atresia, distal skeletal anomalies, hypertrichosis, excess skin, lytic lesions of the skull, atrial septal defect, sensorineural hearing loss, mild joint contractures, dysmorphic facial features, hypertelorism, wavy eyebrows, wide nose, wide mouth, prominent chin, phenotypic overlap with Dubowitz syndrome, microcephaly, dysmorphic facial features, low-set ears, ptosis, low anterior hairline, hypertrichosis, metopic ridging, asymmetric positioning of the globes, posteriorly rotated ears, broad nasal root, long columella, bifid uvula, distally placed thumbs, camptodactyly, prominent fingertip pads, obsessive-compulsive behaviors, hyperactivity, severe myopia, optic nerve asymmetry, conductive hearing loss.", "HYPERPHOSPHATASIA WITH MENTAL RETARDATION SYNDROME 3": "Rare genetic disorder: Autosomal recessive nonsyndromic severe mental retardation. Clinical features include severe motor delay, intellectual disability with poor speech, mild microcephaly, absence seizures, severe hypotonia, disordered sleep pattern, increased serum alkaline phosphatase, brain atrophy, increased gyration, Dandy-Walker malformation, sensorineural hearing loss, atrial septal defect, Hirschsprung disease, cleft palate, broad nasal bridge.", "SMITH-LEMLI-OPITZ SYNDROME": "Clinical features of the rare genetic disorder include microcephaly, mental retardation, hypotonia, incomplete development of male genitalia, short nose with anteverted nostrils, pyloric stenosis, hypospadias, blepharoptosis, micrognathia, polydactyly, cleft palate, mesomelic dwarfism, ambiguous genitalia, webbed neck, highly arched palate, clubfeet, fused fontanels, inclusion cysts of the tongue, widely spaced nipples, oligopapillary renal hypoplasia, severe congenital heart defects, cerebellar hypoplasia, pulmonary, laryngeal, and gallbladder hypoplasia, joint contractures, unilobar lungs, renal hypoplasia, failure to thrive, facial dysmorphism, syndactyly, postaxial polydactyly, Hirschsprung disease, cardiac and renal malformations, low maternal estriol levels, sex reversal, large adrenal glands, female external genitalia, intraabdominal testes, normal internal and external genitalia of the female type, abnormal sequences on the Y chromosome, holoprosencephaly, increased levels of 7-dehydrocholesterol, syndactyly of toes 2 and 3, hypospadias, mental retardation, photosensitivity, abnormal sleep pattern, microcephaly, short or proximally placed thumbs, congenital cardiac abnormalities, atrioventricular septal defect, mild growth retardation, mild developmental delay, ptosis, micrognathia, mild syndactyly of toes 2 and 3, mild facial abnormalities, mild ptosis, anteverted nares, mild micrognathia, mild retrognathia, and delay in diagnosis.", "DHCR7": "Clinical features of the rare genetic disorder include microcephaly, mental retardation, hypotonia, incomplete development of male genitalia, short nose with anteverted nostrils, pyloric stenosis, hypospadias, blepharoptosis, micrognathia, polydactyly, cleft palate, mesomelic dwarfism, ambiguous genitalia, webbed neck, highly arched palate, clubfeet, fused fontanels, inclusion cysts of the tongue, widely spaced nipples, oligopapillary renal hypoplasia, severe congenital heart defects, cerebellar hypoplasia, pulmonary, laryngeal, and gallbladder hypoplasia, joint contractures, unilobar lungs, renal hypoplasia, failure to thrive, facial dysmorphism, syndactyly, postaxial polydactyly, Hirschsprung disease, cardiac and renal malformations, low maternal estriol levels, sex reversal, large adrenal glands, female external genitalia, intraabdominal testes, normal internal and external genitalia of the female type, abnormal sequences on the Y chromosome, holoprosencephaly, increased levels of 7-dehydrocholesterol, syndactyly of toes 2 and 3, hypospadias, mental retardation, photosensitivity, abnormal sleep pattern, microcephaly, short or proximally placed thumbs, congenital cardiac abnormalities, mild growth retardation, mild developmental delay, ptosis, mild syndactyly of toes 2 and 3, mild facial abnormalities, retrognathia, delay in diagnosis, and DHCR7 mutations.", "INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC, TURNER TYPE": "Clinical features of the rare genetic disorder include global developmental delay, impaired intellectual development, low growth parameters at birth, dysmorphic facial features (high forehead, dysplastic low-set ears, hypotelorism, small palpebral fissures, flat nasal bridge, high-arched palate, esotropia, epicanthal folds), hearing impairment, rudimentary scrotum with small penis and cryptorchidism, microcephaly, spasticity, epilepsy, macrocephaly, limited extension of the elbows and tapering fingers, triangular face, malar flatness, blepharophimosis, optic atrophy, esotropia, nystagmus, spastic diplegia, macroorchidism, macrocephaly, decreased muscle mass with spastic diplegia, behavioral problems, seizures, developmental regression, increased serum lactate, mitochondrial defect, flexion deformity of the knees, neonatal hypotonia, microphthalmia, kyphoscoliosis, retinopathy, short corpus callosum, intermittent mild neutropenia, intellectual disability, severe speech delay or absent speech, hypotonia, childhood-onset seizures, microcephaly, short stature, small hands and feet with brachydactyly and tapering fingers, low birth weight, overlapping toes, craniosynostosis, scoliosis, knee contractures, hearing loss, hyperpilosity, sleep disorder, cryptorchidism, hyperactivity/autistic/stereotypic features, dysmorphic features (long face, broad nasal tip, short philtrum, low-set or posteriorly rotated ears, deep-set eyes, epicanthal folds, blepharophimosis, strabismus), and skewed X-inactivation ratio in females.", "ORC1": "Clinical features of this rare genetic disorder, known as Meier-Gorlin syndrome or ear-patella-short stature syndrome (EPS), include bilateral microtia (small ears), absent patellae, short stature, poor weight gain, and characteristic facial features. Other skeletal anomalies may include joint hyperextensibility, abnormal modeling of the glenoid fossas, and clinodactyly. Delayed bone age, proportional dwarfism, microcephaly, and craniofacial anomalies are also observed. Additional features may include deafness, congenital labyrinthine anomalies, and hypoplastic genitalia. Growth hormone deficiency and complications such as emphysema and hernia may also be present.", "MEIER-GORLIN SYNDROME 2": "Text 1: Phenotype characteristics include intrauterine growth retardation, microcephaly, dolichocephaly, micrognathia, flat philtrum, hypoplasia of nasal alae, microtia, prominent clitoris, camptodactyly, hyperextensible joints, normal psychomotor development, high-pitched voices.\n\nText 2: Phenotype characteristics include pre- and postnatal growth retardation, microtia, hypoplastic or absent patellae, feeding difficulties, tracheomalacia, bronchomalacia, narrow thoracic cage, congenital emphysema, clubfoot, breast hypoplasia, hypoplastic labia majora.", "MEIER-GORLIN SYNDROME 4": "Meier-Gorlin syndrome: microcephaly, high intellect, absent/hypoplastic patella, abnormal glenoid fossa, hook-shaped clavicles, long slender bones, mammary gland hypoplasia, feeding difficulties, patent ductus arteriosus, short stature, microtia, hypoplastic labia majora, delayed breast development.", "CDC6": "Crucial phenotype characteristics: \n- Below 3rd centile for weight, length, and head circumference at birth\n- Bilateral microtia, small triangular face, and submucous cleft palate\n- Gastroesophageal reflux and feeding problems in the first year of life\n- Height, weight, and head circumference still below 3rd centile at 4 years\n- Additional craniofacial anomalies: prominent metopic suture, long philtrum, full lips, small teeth, micrognathia, absent helices, hypoplastic lobules, and small external ear canals\n- Micropenis and cryptorchidism\n- Fifth finger and toe clinodactyly\n- Hypermobility of fingers, elbows, shoulders, and knees\n- Absence of patellae confirmed by radiography and ultrasonography\n- Skeletal abnormalities: hypoplastic and irregular epiphyses, elbow dislocation, bone age delay\n- Slightly retarded psychomotor development", "MEIER-GORLIN SYNDROME 3": "Clinical features of the rare genetic disorder include short stature, small external ears, cryptorchidism in males, bone defects (absent or nonossified patellae, femoral asymmetry, coxa valga, abnormal ribs, sacral hypoplasia, skull defect, abnormal sternum), micrognathia, microtia, abnormally formed ears, absent or hypoplastic patellae, hypoplasia of mammary glands, abnormal nuchal translucency, growth restriction, dislocation of knees, gracile bones, clubfeet, shortening of femurs, small thorax, and hypoplastic mandible.", "MUENKE SYNDROME": "Clinical features of this rare genetic disorder include coronal synostosis, abnormalities in the hands and feet (such as thimble-like middle phalanges, coned epiphyses, and fusions), brachydactyly, sensorineural hearing loss, and developmental delay. The disorder is caused by the P250R mutation in the FGFR3 gene and is distinct from other craniosynostosis syndromes. Females with the mutation tend to have a more severe phenotype. The mutation is also associated with cranial and facial abnormalities, hydrocephaly, and cognitive defects. The mutation can be detected through genetic testing.", "ORC6": "Clinical features of the rare genetic disorder include short stature, small external ears, cryptorchidism in males, bone defects (absent or nonossified patellae, femoral asymmetry, coxa valga, abnormal ribs, sacral hypoplasia, skull defect, abnormal sternum), micrognathia, microtia, abnormally formed ears, absent or hypoplastic patellae, hypoplasia of mammary glands, abnormal nuchal translucency, growth restriction, dislocation of knees, gracile bones, clubfeet, shortening of femurs, small thorax, and hypoplastic mandible.", "HUTCHINSON-GILFORD PROGERIA SYNDROME": "Clinical features of the rare genetic disorder, progeria, include a progeroid appearance, disproportionately large head, \"pinched\" facial features, lipodystrophy, stiffness of joints, senile appearance, arteriosclerosis, absence of subcutaneous fat, premature aging, cardiovascular complications, growth impairment, insulin resistance, dilated cardiomyopathy, hypergonadotropic hypogonadism, short stature, loss of subcutaneous fat, hair loss, tooth loss, low bone density, beaked nose, hyperlipidemia, atherosclerosis, and various malignancies.", "SHORT STATURE, FACIAL DYSMORPHISM, AND SKELETAL ANOMALIES WITH OR WITHOUT CARDIAC ANOMALIES 1": "This rare genetic disorder is characterized by short stature, facial dysmorphism, skeletal anomalies, and cardiac malformations. Distinctive craniofacial features include a broad forehead, flat midface, short nose, thin upper lip, and high-arched or cleft palate. Skeletal anomalies include short fifth-digit proximal phalanges, 11 pairs of ribs, and sandal gap. Cardiac malformations include transposition of the great arteries, pulmonary valve stenosis, Ebstein anomaly, and ventricular septal defect. Other features include synophrys, low-set ears, hearing impairment, sternal deformity, delayed bone age, spondylolisthesis, Pierre Robin sequence, cleft palate, and obstructive sleep apnea. Cognitive development is normal, but hypotonia may be observed in infancy. Bone density is generally normal, but osteopenia may occur in some adults.", "BLEPHAROCHEILODONTIC SYNDROME 1": "Clinical features of this rare genetic disorder include ectropion of the lower eyelids, hypertelorism, cleft lip and palate, conical teeth, lagophthalmia (incomplete closure of the eyelids), distichiasis (double row of eyelashes), euryblepharon (abnormally wide lid opening), hypodontia (missing teeth), delayed dentition, hypoplastic nails, clinodactyly, imperforate anus, thyroid disorders, syndactyly, and neural tube defects. Autosomal dominant inheritance is observed, and there may be phenotypic overlap with EEC syndrome and van der Woude syndrome. Mutations in the P63 gene and the interferon regulatory factor-6 gene are potential causes.", "ROBINOW SYNDROME, AUTOSOMAL DOMINANT 3": "Robinow syndrome is a rare genetic disorder characterized by mesomelia, normal intellect, genital hypoplasia, and distinctive facial features including frontal bossing, prominent eyes, and a depressed nasal bridge, known as a 'fetal face'.", "ROBINOW SYNDROME, AUTOSOMAL DOMINANT 2": "Rare genetic disorder: Robinow syndrome\n- Distinctive facial features: frontal bossing, prominent eyes, hypertelorism, small upturned nose, triangular mouth, gingival hyperplasia\n- Skeletal anomalies: mesomelic upper limb shortening, short fingers and toes\n- Other features: small penis, cryptorchidism, conductive hearing impairment, chronic otitis media, calvarium thickening, middle ear cavity narrowing, dysmorphic ossicles, brachydactyly, camptodactyly, clinodactyly, oligodontia, downslanting palpebral fissures, midface hypoplasia, wide and depressed nasal bridge, dental crowding, generalized osteosclerosis, undertubulation of long bones, hypoplastic distal phalanges, increased alkaline phosphatase, macrocephaly, high forehead, anteverted nares, long philtrum, thin upper lip, micrognathia, abnormal ear shape or position, mesomelia, broad first toes and thumbs, pectus anomalies, micropenis, cryptorchidism.", "FZD2": "Omodysplasia is a rare genetic disorder characterized by facial anomalies (depressed nasal bridge, broad base of the nose, long philtrum) and skeletal abnormalities such as short humeri, hypoplastic everted condyle, proximal radioulnar diastasis, and anterolateral dislocation of the head of the radius. Other features include micromelic dwarfism, shallow olecranon fossae, shortened first metacarpals, small laterally displaced patellas, large forehead, hypertelorism, maxillary hypoplasia, and hypoplastic genitalia. Intellectual and motor development are typically normal. Additional findings may include short stature, prominent forehead, flat face, rhizomelic shortening of extremities, inability to pronate and supinate forearms, dental crowding, coxa valga, bicornuate uterus, low-set posteriorly angulated ears, downslanting palpebral fissures, upturned short nose, and short thumbs.", "MAPKAPK5": "Patients with this rare genetic disorder exhibit severe developmental delay, facial and cardiac anomalies, synpolydactyly, and variable brain anomalies. They have limited or no speech, exhibit electroencephalogram abnormalities, and may experience seizures. Eye anomalies, hearing impairment, and congenital heart defects are also common. Other features include short stature, failure to thrive, and common facial dysmorphisms. Brain imaging may reveal hypoplasia of the corpus callosum and dilated fourth ventricle. Some patients may have genitourinary anomalies, hair and nail defects, and abnormal eye findings. Seizures are not reported in these patients.", "USP7": "Rare genetic disorder: Neurodevelopmental disorder associated with de novo heterozygous microdeletions of chromosome 16p13. Common features include developmental delay, intellectual disability, autism spectrum disorder, seizures, cryptorchidism/micropenis, hypotonia, and aggressive behavior. Other features include speech apraxia, dysmorphic features, and poor/absent speech. Patients often require special education. Additional features may include delayed motor development, abnormal gait, behavioral abnormalities, feeding difficulties, sleep disturbances, eye abnormalities, and abnormal brain MRI.", "BOSCH-BOONSTRA-SCHAAF OPTIC ATROPHY SYNDROME": "Clinical features of the rare genetic disorder include optic nerve atrophy, developmental delay, impaired intellectual development, decreased visual acuity, visual field defects, variable optic disc abnormalities, cerebral visual impairment, ocular anomalies (strabismus, latent nystagmus), dysmorphic features (protruding ears, small nasal ridge, high nasal bridge, etc.), hypotonia, obsessive-compulsive disorder, autistic features, impaired intellectual development, oromotor dysfunction, repetitive behavior, autism spectrum disorder, seizures, attention deficit-hyperactivity disorder, hearing defect, spasticity, vomiting, impaired consciousness, myopathic signs, hypoplastic corpus callosum, lactate peak in basal ganglia, thinning of posterior corpus callosum, retrognathia, external ear protrusion, superior verbal abilities, reduced nonverbal abilities, hyperbilirubinemia, pervasive developmental disorder, nonverbal learning disability, generalized joint hyperextensibility, optic nerve hypoplasia, reduced size of optic nerve, retinal nerve fiber layer thinning, developmental delay, myoclonic-astatic seizures, nystagmus, hyperopia, conductive hearing loss, cervicothoracic syringomyelia, macrocephaly, broad forehead, speech delay, vision impairment, alacrima, cortical visual impairment, love of music, high pain tolerance, sleep difficulties, touch sensitivity, congenital disorder of glycosylation type 1c, protein-losing enteropathy, ataxia.", "AARSKOG-SCOTT SYNDROME": "Clinical features of Aarskog syndrome include ocular hypertelorism, anteverted nostrils, broad upper lip, saddle-bag scrotum, ligamentous laxity, hyperextensibility of fingers, genu recurvatum, flat feet, cervical spine hypermobility, neurologic deficits, hand and foot anomalies, umbilical changes, osteochondritis dissecans, macrocytic anemia, hepatomegaly, pulmonary disease, benign intracranial hypertension, alopecia, umbilical abnormalities, lymphedema, disappearance of manifestations in postpubertal males, chronic abdominal pain, congenital heart defects, mental handicap (controversial), X-linked mental retardation, attention deficit-hyperactivity disorder, polymicrogyria, and genitourinary abnormalities.", "HARTSFIELD SYNDROME": "Rare genetic disorder: Hartsfield syndrome\nPhenotype characteristics:\n- Lobar holoprosencephaly\n- Ectrodactyly\n- Cleft lip/palate\n- Hypertelorism\n- Depressed nose\n- Low-set and posteriorly rotated ears\n- Craniosynostosis\n- Loss of digits on hands and feet\n- Absence of right radius\n- Partial separation of cerebral hemispheres\n- Hypoplasia of posterior corpus callosum\n- Absence of septum pellucidum\n- Fusion of frontal lobes\n- Absence of olfactory bulbs and tracts\n- Telecanthus\n- Syndactyly of hands and feet\n- Small frontal bones\n- Fused forebrain\n- Absent olfactory bulbs\n- Hypernatremia\n- Severe psychomotor retardation\n- Phenotypic overlap with EEC syndrome\n- Mental retardation\n- Arhinencephaly\n- Vermian hypoplasia\n- Hypoplasia or agenesis of corpus callosum\n- Cleft lip and/or palate\n- Ectrodactyly (variable)\n- Central diabetes insipidus\n- Hypogonadotropic hypogonadism\n- Variable features: hyper- or hypotelorism, ear abnormalities, cryptorchidism\n- Normal karyotype\n- Broad nasal bridge\n- Megalocornea\n- Ectopic testes\n- Small penis\n- Multiple digital anomalies\n- Poor growth\n- Severe psychomotor retardation\n- Skeletal abnormalities\n- Absence of posterior arches of T1-T3 of spine\n- Semilobar holoprosencephaly\n- Absence of frontal horns of lateral ventricles\n- Abnormal frontal lobe gyration\n- Agenesis of corpus callosum\n- Abnormal basal ganglia\n- Hypoplastic brainstem", "FRASER SYNDROME 1": "Clinical features of the rare genetic disorder, Fraser syndrome, include cryptophthalmos (unilateral or bilateral), absent or malformed lacrimal ducts, middle and outer ear malformations, high palate, cleavage along the midplane of nares and tongue, hypertelorism, laryngeal stenosis, syndactyly, wide separation of symphysis pubis, displacement of umbilicus and nipples, primitive mesentery of small bowel, maldeveloped kidneys, fusion of labia and enlargement of clitoris, and bicornuate uterus and malformed fallopian tubes. Consanguinity is observed in some cases. Other associated features include deafness, undescended testes, small penis with hypospadias, gonadal dysgenesis, and pulmonary hyperplasia. Clinical variability and phenotypic variation are noted, suggesting possible genetic modifiers.", "OCULODENTODIGITAL DYSPLASIA": "Clinical features of the rare genetic disorder include bilateral microphthalmia, abnormally small nose, hypotrichosis, dental anomalies, fifth finger camptodactyly, syndactyly of the fourth and fifth fingers, missing toe phalanges, craniofacial deformity, enamelogenesis imperfecta, widened phalanges and metacarpals, spastic paraplegia, neurogenic bladder, conductive deafness, abnormal white matter on MRI, progressive paraplegia, leukodystrophic changes, cognitive impairment, skin, hair, and nail abnormalities, curly hair, trichorrhexis nodosa, keratoderma, dental anomalies, lymphedema, microphthalmia, microdontia, poor enamel, preaxial polydactyly, nanophthalmos, thin hypoplastic nose, inverted palate, optic nerve and retinal dysplasia, and ciliary body cysts.", "CATEL-MANZKE SYNDROME": "Clinical features of Catel-Manzke syndrome include:\n- Clefting of the hard palate, glossoptosis, and micrognathia (Pierre Robin anomaly)\n- Accessory ossification center at the base of the proximal phalanx of the index finger causing bilateral clinodactyly\n- Hypernasal speech due to a small defect remaining in the hard palate\n- Reduced mobility of the index fingers, but ability to grasp objects with the thumb and forefinger\n- Increasing contractures of the little fingers\n- Radiographic findings of fused accessory bones with the proximal phalanges and metacarpal bones\n- Short distal phalanges of the index fingers and flexed fingers 2 to 4\n- Short stature, developmental delay, and skeletal anomalies\n- Various additional congenital abnormalities such as cardiac defects, talipes, knee dislocation, and joint laxity\n- Presence of an extra bone between the second metacarpal and proximal phalanx causing radial deviation of the index fingers\n- Possible association with mandibular hypoplasia, cleft palate, and airway obstruction\n- Genetic mutations in the TGDS gene", "KABUKI SYNDROME 2": "Kabuki syndrome is characterized by long palpebral fissures, lateral eversion of the lower eyelid, intellectual disability, long halluces, sparse eyebrows, long eyelashes, strabismus, large ears, persistent fetal fingertip pads, aortic coarctation, areolar fullness in infancy, hirsutism, feeding problems, hypoglycemia, motor delay, speech delay, impaired intellectual development, cardiovascular malformations, genitourinary anomalies, palate and dental anomalies, hearing loss, strabismus, recurrent infections, hyperinsulinism, seizures, joint hypermobility, and ectodermal abnormalities. Males with Kabuki syndrome have shorter birth lengths, higher frequency of severely impaired intellectual development, and more gastrointestinal problems compared to females.", "FRONTOMETAPHYSEAL DYSPLASIA 2": "Clinical features of the rare genetic disorder include:\n- Facial characteristics: prominent supraorbital ridges, downslanting palpebral fissures, hypertelorism, broad nasal bridge, small pointed chin\n- Skeletal abnormalities: underdeveloped sinuses, luxation of the radial head, small lateral epicondyle of the femora, underdevelopment of the carpals and tarsals, undermodeling of the metacarpals, metatarsals, and phalanges, dense skull, undermodeled and deformed ribs, splaying of the metaphyses\n- Progressive scoliosis\n- Hearing loss\n- Urogenital anomalies\n- Keloid formation\n- Other uncommon features: hypertrophic keloid scars, coxa valga, pes equinovarus, large joint dislocations (primarily of the hips), muscular underdevelopment, cleft palate, hirsutism, intellectual disability, eye abnormalities (thickening or opacification of the cornea, absent anterior eye chamber)", "CAREY-FINEMAN-ZITER SYNDROME": "Clinical features of the rare genetic disorder, Carey-Fineman-Ziter syndrome (CFZS), include hypotonia, Moebius sequence, Pierre Robin sequence, unusual face, growth delay, gavage feeding, normal intelligence, scoliosis, restrictive lung disease, gastrointestinal disturbance, villous atrophy, nocturnal hypoventilation, pulmonary hypertension, craniofacial anomalies, micrognathia, myopathy, macrocephaly, developmental delay, hydronephrosis, hypospadias, pons and brainstem abnormalities, absence of pectoralis major muscle, laryngostenosis, arterial hypertension, reduced white matter, brainstem involvement, clubfeet, and acral anomalies. CFZS may have a higher risk of mental disability and recurrence. Other features include plagiocephaly, flat nasal root, epicanthus, ptosis, cleft palate, glossoptosis, hypotonia, facial palsy, oculomotor palsy, absent swallowing and speech, enlarged ventricles, subependymal heterotopia, thinning of white matter, long tapered fingers, talipes equinovarus, atrial septal defect, abnormal temporomandibular joint function, muscle weakness, delayed motor milestones, contractures, poor growth, feeding problems, ptosis, high-arched or cleft palate, thin neck, pectoralis hypoplasia, hypoglossia, scoliosis, cryptorchidism, myopathic changes, increased serum creatine kinase, congenital fiber-type disproportion, muscle atrophy and fatty replacement, dysphagia, gastrointestinal symptoms, dysmorphic features, spinal rigidity, epilepsy, sensorineural hearing loss, cataract, glaucoma, and necrotizing myopathy.", "OSTEOGENESIS IMPERFECTA, TYPE XX": "1. Osteogenesis imperfecta: progressive deforming type\n2. Fractures observed prenatally and within first 2 years of life\n3. Bisphosphonate treatment unsuccessful\n4. Respiratory failure leading to death in 3 patients\n5. Nonambulatory in oldest affected individuals\n6. Bluish sclerae in youngest individuals\n7. Disorganized dentition and/or oligodontia in older individuals\n8. Global developmental delay or intellectual disability in 3 individuals\n\n1. Osteogenesis imperfecta type XX\n2. Stillbirths occurred after prenatal diagnosis of skeletal disorder\n3. Triangular face, blue sclerae, retrognathia, micromelia, angulated long bones, bilateral clubfeet\n4. Narrow thorax, severe lung hypoplasia, congestion of venous inflow tract of heart\n5. Hepatomegaly and fetal hydrops\n6. Multiple rib fractures and overtubulation of long bones on fetal autopsy\n7. Impaired osseous development with altered osteocyte morphology\n8. Reduced canalicular connectivity\n9. Impaired and heterogeneous matrix mineralization", "KOOLEN-DE VRIES SYNDROME": "Clinical features of the rare genetic disorder, 17q21.31 microdeletion syndrome or Koolen-De Vries syndrome, include mental retardation, hypotonia, and characteristic facial features such as long face, ptosis, large and low-set ears, bulbous nasal tip, and broad chin. Other common features include delayed motor development, nasal speech, amiable disposition, joint hypermobility, cardiac defects, urologic anomalies, CNS anomalies, ectodermal anomalies, and seizures. The syndrome can be caused by deletions encompassing the MAPT and CRHR1 genes or truncating mutations in the KANSL1 gene. Seizures occur in about 50% of patients and are often focal impaired awareness seizures with autonomic signs. Structural brain abnormalities, delayed development, and intellectual disability are also present.", "INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 99, SYNDROMIC, FEMALE-RESTRICTED": "Clinical features of the rare genetic disorder described in the texts include delayed psychomotor development, mild to moderate intellectual disability, language delay, hypotonia, feeding and breathing difficulties, joint laxity, short stature, scoliosis, hip dysplasia, postaxial polydactyly, pes cavus, anal atresia, hearing loss, facial asymmetry, prominent forehead, bitemporal narrowing, short palpebral fissures, eye abnormalities, low or broad nasal bridge, prominent nose with flared nasal alae, thin upper lip, smooth long philtrum, dental abnormalities, low-set posteriorly rotated ears, cataracts, astigmatism, strabismus, myopia, hypermetropia, brachycephaly, up- or downslanting palpebral fissures, choanal atresia, pronounced nasolabial folds, small hands and feet, tapering fingers, asymmetric hypomastia, mild cardiac defects, urogenital anomalies, thyroid hormone abnormalities, hypertrichosis, sacral dimple, seizures, recurrent respiratory tract infections, malignancy, hypoplastic corpus callosum, cerebellar hypoplasia, enlarged ventricles, abnormal gyral pattern in the frontal lobes, Dandy-Walker malformation, and skin pigmentary abnormalities.", "AHDC1": "Rare genetic disorder: Xia-Gibbs syndrome\nPhenotype characteristics:\n- Impaired intellectual development, failure to thrive, hypotonia, delayed psychomotor development\n- Absent or poor expressive language, mild dysmorphic features (low-set or protuberant ears, flat nasal bridge, esotropia, hypertelorism, up- or downslanting palpebral fissures, micrognathia)\n- Obstructive sleep apnea, laryngomalacia or tracheomalacia\n- Brain abnormalities (hypoplasia of corpus callosum, simplified gyral pattern, delayed myelination, retrocerebellar cyst)\n- De novo mutations in AHDC1 gene, developmental delay, hypotonia, dysmorphisms, growth or feeding issues, cognitive delay, ataxia, autism\n- Brain abnormalities (corpus callosum abnormalities, subependymal cysts, hypomyelination)\n- Other features: omphalocele, macular dystrophy, clubfoot, craniosynostosis, cochlear nerve dysfunction, hypermobile joints\n- Hypotonia, developmental delay, dysmorphic features (midface hypoplasia, hypertelorism, micrognathia, upslanting palpebral fissures), laryngomalacia\n- Brain abnormalities (frontal and temporal cortical atrophy, loss of posterior ventricular white matter)\n- Speech and motor developmental delay, hypotonia, hypertonia, impaired intellectual development, growth or feeding issues, anatomic upper airway obstruction, joint laxity, scoliosis, lumbar lordosis\n- Structural brain abnormalities (corpus callosum abnormalities, cerebral atrophy, ventriculomegaly, diffuse cerebral atrophy, small pituitary)\n- Craniosynostosis, seizures, cystic encephalomalacia, elevated calcium and phosphorus, microcephaly, brachycephaly, lack of speech, hairy forehead, thin upper lip, strabismus, almond-shaped eyes, laryngomalacia", "SIFRIM-HITZ-WEISS SYNDROME": "Clinical features of the rare genetic disorder described in the texts include congenital heart defects (such as tetralogy of Fallot, aortic coarctation, and septal defects), early global neurodevelopmental delay, dysmorphic features (such as coarse facies, abnormal facial shape, epicanthal folds, ptosis, astigmatism, and ear abnormalities), additional abnormalities (such as omphalocele, cryptorchidism, ambiguous genitalia, anteriorly placed anus, vesicoureteral reflux, skeletal abnormalities, postaxial polydactyly, wormian bones), hearing impairment, Chiari malformation, macrocephaly, widely spaced eyes, square-shaped face, palatal anomalies, short stature, hypogonadotropic hypogonadism, cryptorchidism, micropenis, cervical vertebral fusions, tarsal coalitions, patent ductus arteriosus, moyamoya disease, chronic renal insufficiency, and enlarged ventricles. Mutation in the CHD4 gene is associated with ischemic stroke due to bilateral moyamoya angiopathy and hypertension.", "INTELLECTUAL DEVELOPMENTAL DISORDER WITH DYSMORPHIC FACIES AND PTOSIS": "Rare genetic disorder: Global developmental delay, intellectual disability, expressive language impairment, dysmorphic facial features (broad forehead, flat facial profile, round face, broad nasal root, fleshy nose, widely spaced eyes with downslanting palpebral fissures, blepharophimosis, ptosis, short philtrum, small or wide mouth, abnormal ears), neonatal feeding difficulties, hypotonia, delayed motor skills, seizures, joint hypermobility, cervical spinal fusion abnormalities, brain abnormalities (white matter abnormalities, decreased volume, thin corpus callosum). Additional features: Growth retardation, ptosis, microcephaly, clubfeet, edema, poor feeding, agenesis of corpus callosum, brachymetacarpia, delayed psychomotor development, speech delay, blepharophimosis, hypotonia, short stature, strabismus, camptodactyly, seizures.", "MEIER-GORLIN SYNDROME 6": "Patients with this rare genetic disorder, known as Meier-Gorlin syndrome, exhibit several crucial phenotype characteristics. These include primordial dwarfism, microtia (underdeveloped ears), and absent patellae (kneecaps). Other common features include feeding problems, hearing loss, delayed bone age, craniofacial abnormalities (such as frontal bossing and downslanting palpebral fissures), and skeletal abnormalities (such as midphalangeal hypoplasia and planovalgus feet). Additional symptoms may include respiratory issues, cognitive delays, and genital abnormalities.", "INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC 33": "Rare X-linked neurodevelopmental syndrome characterized by global developmental delay, intellectual disability, delayed speech, hypotonia, joint hypermobility, growth retardation, oropharyngeal dysphagia. Facial dysmorphic features include prominent supraorbital ridges, downslanting palpebral fissures, deep-set eyes, sagging cheeks, long philtrum, low-set and protruding ears, long face, high-arched palate, thin upper lip, pointed chin, and broad upturned nose. Other features include hearing impairment, microcephaly, hypoplasia of the corpus callosum, spastic diplegia, dystonic movements, tremors, seizures (in some cases), autistic behaviors, and a characteristic gluteal crease with a sacral caudal remnant.", "HYPOTONIA, INFANTILE, WITH PSYCHOMOTOR RETARDATION AND CHARACTERISTIC FACIES 2": "Severe neurodevelopmental disorder with hypotonia, global developmental delay, intellectual disability, feeding difficulties, seizures, and dysmorphic features. Decreased head circumference, cerebral atrophy, and abnormal EEG. Also, severe hypotonia, developmental delay, failure to thrive, microcephaly, dysmorphic features, and abnormal brain imaging. No epilepsy, but abnormal EEG. Marked hypotonia, failure to thrive, global developmental delay, dyskinesia, seizures, and dysmorphic features. Abnormal EEG, but no specific brain imaging findings.", "KLEEFSTRA SYNDROME 2": "Kleefstra syndrome-2: Delayed psychomotor development, low IQ, no speech development, hyperactivity, aggressiveness, dysmorphic features (midface hypoplasia, synophrys, upward slanting palpebral fissures, etc.), short stature, mild microcephaly.\n\nKLEFS2: Delayed psychomotor development, intellectual disability, speech delay, autism features, behavioral problems, childhood hypotonia, seizures, scoliosis/kyphosis, dysmorphic features (flattened midface, prominent eyebrows, everted lower lip, etc.).\n\nKMT2C gene mutations: Severe intellectual disability, global developmental delay, poor or absent speech, poor overall growth, dysmorphic features (downslanting palpebral fissures, ptosis, arched eyebrows, etc.), additional complications (duplicated thumb, hydrocephalus, developmental regression).", "MENTAL RETARDATION, AUTOSOMAL RECESSIVE 65": "Phenotype characteristics of the rare genetic disorder described in the texts include: moderate to severe developmental delay, impaired intellectual development, neonatal feeding difficulties, poor overall growth, delayed walking and speech, learning difficulties, dysmorphic facial features (such as square face, downslanting palpebral fissures, ptosis, prominent metopic ridge, high nasal bridge, smooth philtrum, low-hanging columella, thin lips, and dysmorphic ears), vision problems (myopia, astigmatism, and strabismus), atrial septal defect, cryptorchidism, hypospadias, dolichocephaly, supernumerary nipple, inguinal hernia, camptodactyly of the fourth and fifth fingers, thin corpus callosum (in one patient), absence of seizures, developmental delay, specific learning disability, attention deficit disorder, sleep disturbance, generalized joint laxity, and macrocephaly at birth (with normal brain imaging).", "MENTAL RETARDATION, AUTOSOMAL DOMINANT 51": "Patients with a rare genetic disorder associated with variants in the KMT5B gene exhibit cognitive neurodevelopmental disorders, developmental delay, intellectual disability, speech and motor delays, autism spectrum disorder, behavioral abnormalities, febrile seizures, dysmorphic facial features, cryptorchidism, foot deformities, sleep difficulties, tall stature, mild brain anomalies, and variable immunodeficiency. Another group of patients with MRD51 have global developmental delay, delayed walking, intellectual disability, poor language, dysmorphic features including facial asymmetry, large head circumference, frontal bossing, epicanthal folds, posteriorly rotated ears, proptosis, microtia, and some had seizures.", "YOU-HOOVER-FONG SYNDROME": "Patients with this rare genetic disorder exhibit severely delayed global development, microcephaly, abnormal balance, and a movement disorder. They may also experience poor feeding, hypotonia, hearing loss, cortical visual impairment, speech difficulties, brachydactyly, clinodactyly, toe syndactyly, and congenital heart disease. Dysmorphic features include blue sclerae, joint laxity, and pectus carinatum. Other variable features may include cleft palate, kyphoscoliosis, abnormal sleep patterns, and rotary nystagmus. Seizures are rare, and brain imaging appears normal in most cases.", "COFFIN-SIRIS SYNDROME 6": "Patients with this rare genetic disorder exhibit a range of clinical features including intellectual disability, short stature, dysmorphic facial features, and failure to thrive. Common symptoms include gastroesophageal reflux, constipation, and wormian bones of the skull. Other characteristics include micrognathia or retrognathia, low-set or posteriorly rotated ears, epicanthal folds, downslanting palpebral fissures, high-arched palate, frontal bossing, and behavioral issues such as ADHD, tics, anxiety, and obsessions. Seizures are not observed. Additional features may include pectus excavatum, kyphoscoliosis, conductive hearing loss, cleft palate, diaphragmatic eventration, and atrial septal defect.", "ACROMICRIC DYSPLASIA": "Clinical features of the rare genetic disorder described in the texts include mild facial anomalies, markedly shortened hands and feet, severe growth retardation, short and stubby metacarpals and phalanges, notches on certain bones, disorganization of growth cartilage, normal intelligence, mild dysmorphic features, well-developed muscles, hoarse voice, joint limitations, ear, tracheal, and respiratory complications, spine abnormalities, and occasional x-ray abnormalities. The disorder appears to be sporadic in most cases, but vertical transmission was observed in a few families, suggesting an autosomal dominant inheritance pattern.", "MEIER-GORLIN SYNDROME 7": "Patients with biallelic mutations in the CDC45 gene exhibit a range of clinical features, including syndromic coronal craniosynostosis and severe growth restriction. The classic triad of Meier-Gorlin syndrome features, including short stature, microtia, and absent or hypoplastic patellae, is present in some patients. Craniosynostosis is also common, with varying severity. Some patients present primarily with craniosynostosis and exhibit mild Meier-Gorlin syndrome features. Thin eyebrows, growth failure, microcephaly, and anal abnormalities are observed in many patients.", "CHOPS SYNDROME": "Children with this rare genetic disorder have delayed psychomotor development, intellectual disability, short stature, obesity, and dysmorphic facial features. These facial features include a round face, proptosis, hypertelorism, thick eyebrows and hair, long eyelashes, short nose, and downturned corners of the mouth. They may also have heart defects, pulmonary manifestations such as chronic lung disease and recurrent aspiration pneumonia, skeletal abnormalities, kidney abnormalities, gastroesophageal reflux, and other associated conditions like cataracts and hearing loss. Some features resemble Cornelia de Lange syndrome.", "HYPOTONIA, ATAXIA, AND DELAYED DEVELOPMENT SYNDROME": "Rare genetic disorder: Global developmental delay, intellectual disability, speech delay apparent from infancy. Truncal hypotonia, ataxia. Mild dysmorphic features: tall forehead, long face, deep philtrum, high nasal bridge, straight eyebrows, strabismus, low-set and posteriorly rotated ears, short/broad chin. Seizures in some cases. Brain imaging normal or cerebellar hypoplasia. Reduced fetal movements in some cases. Dysmorphic features: myopathic facies, overfolding of ears, low-set ears, anteverted nostrils, epicanthal folds, downturned corners of mouth, strabismus. Additional features: micropenis, cryptorchidism, testicular failure, reduced volume of labia majora. Brain imaging: cerebellar hypoplasia or normal. Pain insensitivity, stereotypic behavior. Other features: astigmatism, gastroesophageal reflux, inverted nipples, vesicoureteral reflux, dysmetria, apraxia. Delayed language and motor development, speech delay, expressive language delay. Motor features: hypotonia, delayed motor development, ataxia, incoordination, hypertonia. EEG abnormalities, seizures. Decreased pain response, sensory features. Neuropsychiatric findings: autistic features, formally diagnosed autism. Cerebellar abnormalities. Craniofacial features, constipation, gastroesophageal reflux, strabismus. Urinary tract infections, recurrent UTIs.", "INTELLECTUAL DEVELOPMENTAL DISORDER WITH HYPOTONIA AND BEHAVIORAL ABNORMALITIES": "Patients with IDDHBA, a rare genetic disorder, exhibit various clinical features. These include hypotonia, feeding difficulties with episodic vomiting, global developmental delay, and delayed motor development. Congenital heart defects, delayed walking, speech delay, and impaired intellectual development are also common. Many patients have concurrent diagnoses of autism and/or ADHD, along with other behavioral anomalies. Ocular anomalies, impaired vision, and dysmorphic features such as brachycephaly and hypertelorism are often observed. Brain imaging may show agenesis or thin corpus callosum.", "KOSAKI OVERGROWTH SYNDROME": "Rare genetic disorder: Overgrowth syndrome with distinctive facial features, hyperelastic fragile skin, scoliosis, white matter lesions, and neurologic deterioration. Accelerated linear growth, mandibular tumor, and myofibroma. Prominent forehead, proptosis, downslanting palpebral fissures, broad nasal bridge, thin upper lip, and pointed chin. Recurrent episodes of depression, anxiety, and schizophrenic symptoms. Abnormal cranial shape, thoracolumbar scoliosis, and granular pattern on x-ray. Periventricular white matter lesions on MRI. Impaired intellectual development, long fingers and toes, hypertelorism, and thinning of nasal ridge.", "OKUR-CHUNG NEURODEVELOPMENTAL SYNDROME": "Common phenotype characteristics of the described rare genetic disorder include:\n- Developmental delay and intellectual disability\n- Behavioral problems and delayed speech\n- Hypotonia\n- Gastrointestinal problems such as dysphagia, gastric reflux, or constipation\n- Microcephaly and pachygyria on brain imaging\n- Dysmorphic features including low-set and folded ears, arched eyebrows, ptosis, epicanthal folds, hypertelorism, broad nasal bridge, upturned nose, high palate, thin upper lip, protruding tongue, clinodactyly, and brachydactyly\n- Behavioral problems such as tantrums, volatile mood, clapping, hand-flapping, and attention deficit-hyperactivity disorder features\n- Scoliosis and/or joint laxity\n- Immunologic findings of hypogammaglobulinemia and mild IgA or IgG deficiency\n- Ataxia, seizures, and sleeping difficulties\n- Impaired social responsiveness and developmental delay in most areas\n- Facial features including microcephaly, hypertelorism, epicanthic folds, ptosis, low-set ears, broad nasal bridge, and round face\n- Neurodevelopmental delay, gastrointestinal issues, musculoskeletal issues, and immunologic abnormalities\n- Impaired intellectual development and short stature\n- Neonatal hypotonia, autistic spectrum traits, swallowing difficulties, and congenital heart disease\n- Malar flattening, depressed nasal bridge, short nose, thin upper vermilion, epicanthus, short philtrum, and widely spaced teeth\n- Relative macrocephaly, hypertrichosis, downslanting palpebral fissures, and bulbous nose\n- Abnormal MRI findings including reduced anterior pituitary gland and delayed myelination.", "HYPOTONIA, INFANTILE, WITH PSYCHOMOTOR RETARDATION AND CHARACTERISTIC FACIES 3": "Rare genetic disorder: Profound developmental disability, severe hypotonia, respiratory insufficiency, feeding tube placement, bitemporal narrowing, arched eyebrows, deep-set eyes, high nasal bridge, cupid bow, coarse facial features, macroglossia, gingival hyperplasia, decreased or absent reflexes, seizures, cortical visual impairment, ventriculomegaly, cerebral atrophy, thinning of corpus callosum, small basal ganglia, cerebellar hypoplasia, periventricular white matter abnormalities, axonal neuropathy, decreased activities of mitochondrial respiratory chain enzymes, sloped forehead, macrocephaly, bulbous nose, tented upper lip, diffuse brain atrophy, enlarged ventricles, mild cognitive impairment.", "ELSAHY-WATERS SYNDROME": "Clinical features of the rare genetic disorder include mental retardation, maxillary hypoplasia, mandibular prognathism, dental cysts, broad nasal bridge, hypertelorism, bifid uvula or partial cleft palate, pectus excavatum, fused cervical spinous processes, penoscrotal hypospadias, and Schmorl nodes. Other characteristics may include saddle nose deformity, midline nasal cleft, thick philtrum, prominent lips, coloboma of the upper lids, midface hypoplasia, pectus carinatum, hearing loss, brachycephaly, facial asymmetry, high forehead, synophrys, telecanthus, proptosis, blepharochalasis, thoracolumbar scoliosis, submucous cleft soft palate, small penis with hypospadias, delayed dental eruption, synophrys discontinuation, absent upper incisors, short fingers, widely spaced nipples, anteriorly placed and stenotic anus, bifid scrotum, cryptorchidism, bitemporal narrowing, low-set posteriorly rotated ears, downslanting palpebral fissures, bulbous tip of nose, megalocornea, flat malar regions, glaucoma, cataract, phthisis bulbi, partial cutaneous syndactyly, impacted teeth with dentigerous cyst, malocclusion, high-arched palate, extensive caries, small cleft of the upper eyelid, exposure keratitis, and megalocornea with large optic cups.", "NEURODEVELOPMENTAL DISORDER WITH OR WITHOUT ANOMALIES OF THE BRAIN, EYE, OR HEART": "Rare genetic disorder: delayed psychomotor development, intellectual disability, autistic spectrum disorder, congenital abnormalities, growth retardation, feeding difficulties, hypotonia, behavioral problems, ophthalmologic abnormalities, congenital heart defects, genitourinary defects, dysmorphic features, ventriculomegaly, thin corpus callosum, small cerebellar vermis, decreased white matter, 1p36 deletions involving RERE, neurodevelopmental findings, structural defects, eye defects, congenital heart defects, sensorineural hearing loss, scoliosis.", "ACROCALLOSAL SYNDROME": "Clinical features of the rare genetic disorder, acrocallosal syndrome (ACLS), include postaxial polydactyly, hallux duplication, macrocephaly, absence of corpus callosum, and severe mental retardation. Other common characteristics are hypertelorism, presence of intracranial cysts, and dysmorphic facial features such as prominent forehead and hypertelorism. ACLS may also be associated with other anomalies like agenesis of the corpus callosum, preaxial polydactyly, and heart defects. Some cases have shown a possible genetic link to the Greig cephalopolysyndactyly syndrome. Joubert syndrome-12, another related disorder, presents with mental retardation, molar tooth sign on brain MRI, dysmorphic facial features, and polydactyly.", "ARTHROGRYPOSIS, DISTAL, TYPE 3": "Clinical features of the rare genetic disorder include: clubfoot, camptodactyly, cleft palate, bifid uvula, foot anomalies, holes in the palate, short stature, ptosis, pterygium colli, vertebral anomalies, ophthalmoplegia, retinopathy, deep-set eyes, triangular face, prominent ears, limited eye movements, rigid back, stiff walk, anteverted hunched shoulders, pectus excavatum, long fingers with limited flexion, absent phalangeal creases, abnormal retinal pigmentation, metacarpophalangeal and interphalangeal joint contractures, elbow, shoulder, knee, and ankle joint contractures, distinct facial phenotype, mild intellectual disability, delay in psychomotor development, and arthrogryposis multiplex.", "HOLOPROSENCEPHALY 3": "Clinical features of the rare genetic disorder include holoprosencephaly, single central maxillary incisor, hypotelorism, bifid uvula, pituitary deficiency, microcephaly, refractive errors, small corneal diameter, coloboma, foveal hypoplasia, blepharoptosis, hyperopia, strabismus, astigmatism, depressed nasal bridge, and brain malformations. These features can vary in severity and may be present in different combinations.", "JOUBERT SYNDROME 17": "Rare genetic disorder: Joubert syndrome. Clinical features include episodic hyperpnea, abnormal eye movements, ataxia, global psychomotor retardation, agenesis of cerebellar vermis, cognitive impairment, oculomotor apraxia, breathing abnormalities, limb abnormalities (polydactyly, syndactyly), molar tooth sign on brain MRI. Mutations in C5ORF42 gene associated with polydactyly.", "SHASHI-PENA SYNDROME": "Patients with this rare genetic disorder exhibit developmental delay, delayed walking and speech, hypotonia, behavioral problems, and intellectual disability. They often have feeding difficulties, macrocephaly, and dysmorphic features such as hypertelorism, arched eyebrows, and broad nasal tip. Other features include cardiac defects, hypoglycemia, skeletal abnormalities, and seizures. Brain imaging shows abnormalities in most patients. This disorder shares phenotypic similarities with Bohring-Opitz syndrome and Bainbridge-Ropers syndrome, caused by mutations in ASXL1 and ASXL3 genes, respectively.", "HYPERPHOSPHATASIA WITH MENTAL RETARDATION SYNDROME 1": "Rare genetic disorder characterized by severe mental retardation, seizures, and elevated alkaline phosphatase. Other features include neurologic abnormalities, delayed motor and speech development, hypoplastic terminal phalanges, hypoplastic nails, hypotonia, delayed myelinization in the brain, distinct facial features (hypertelorism, downturned corners of the mouth), and various congenital anomalies (anteriorly displaced anus, clefting of the palate, anovestibular fistula, ventricular septal defect). Patients may have intracellular inclusions in some tissues. The disorder is associated with hyperphosphatasia and is distinct from Coffin-Siris syndrome.", "NEURODEVELOPMENTAL DISORDER WITH EPILEPSY, CATARACTS, FEEDING DIFFICULTIES, AND DELAYED BRAIN MYELINATION": "Patients with a neurodevelopmental disorder caused by a mutation in the NACC1 gene exhibit severe to profound intellectual disability, global developmental delay, feeding difficulties, and failure to thrive. Some patients have hypotonia, seizures with developmental regression, and are unable to sit, walk, speak, or track visually. Other features include cataracts, sleep disorders, hand movements, irritability, and breath-holding spells. Microcephaly and dysmorphic features are present in some patients, with a broad nasal tip being the only common feature. Brain imaging shows cerebral atrophy, reduced white matter, and delayed myelination. Some patients may also have spasticity, joint contractures, and scoliosis.", "CEREBELLAR ATROPHY, VISUAL IMPAIRMENT, AND PSYCHOMOTOR RETARDATION": "Severe neurodegenerative disorder apparent since birth, global developmental delay, speech delay, hypotonia, cerebellar atrophy, short/atrophic corpus callosum, profound intellectual disability, progressive microcephaly, increased tone in extremities, hyporeflexia, dystonic posturing, scoliosis, cerebral atrophy, dysmorphic features (deep-set eyes, gingival hyperplasia, retrognathia, short philtrum), ophthalmologic abnormalities (cortical visual impairment, abnormal VEP and ERG, esotropia, strabismus, astigmatism), possible subclinical seizures. Families of European, Turkish, and Saudi Arabian origin, with two being consanguineous.", "SKRABAN-DEARDORFF SYNDROME": "Rare genetic disorder: Intellectual disability, global developmental delay (mild to severe), speech delay, motor delay (sitting, crawling, walking), hypotonia, abnormal gait, seizures (varied types), brain abnormalities (dilated ventricles, thin corpus callosum, etc.), coarse facial features (prominent maxilla, wide mouth, etc.), gastrointestinal issues (constipation, reflux), otitis media, cardiac defects (rare), happy demeanor, possible overlap with chromosome 1q41-q42 deletion syndrome.", "MENTAL RETARDATION, AUTOSOMAL DOMINANT 48": "Clinical features of the rare genetic disorder described in the texts include global developmental delay, moderate to severe intellectual disability, poor or absent speech, delayed or impaired walking, poor feeding, hypotonia, seizures, behavioral problems, stereotypical movements, microcephaly, dysmorphic facial features, sensorineural hearing loss, mild visual impairment, abnormal brain imaging (including cerebellar hypoplasia, cerebellar dysplasia, hypoplasia of the corpus callosum, enlarged ventricles, mega cisterna magna, thin brainstem, and polymicrogyria), nonspecific periventricular white matter lesions, hypospadias, cardiac abnormalities (such as ventricular septal defect, atrial septal defect, patent ductus arteriosus, and tricuspid valve insufficiency), recurrent infections, and eczema.", "NEURODEVELOPMENTAL DISORDER WITH DYSMORPHIC FACIES AND DISTAL LIMB ANOMALIES": "Patients with this rare genetic disorder exhibit delayed psychomotor development, intellectual disability, delayed speech, mild to severe impairment, mild postnatal microcephaly, poor overall growth, short stature, skeletal anomalies (such as pes planus, sandal gap, clinodactyly), dysmorphic facial features (including lateral flaring of the eyebrows, hypertelorism, prominent nose), ocular abnormalities (such as strabismus, myopia), pituitary hypoplasia, nonspecific white matter abnormalities, and absence of seizures. Additionally, they may experience developmental delay, speech delay, small head circumference, motor delay, hypotonia, dysmorphic features, seizures, EEG abnormalities, mild structural brain abnormalities, ophthalmologic abnormalities (exotropia, strabismus, myopia), skeletal abnormalities (scoliosis, spinal anomalies, delayed bone age), and limb anomalies (cutaneous syndactyly, sandal gap).", "JOUBERT SYNDROME 32": "Rare genetic disorder: developmental delay, intellectual disability, cerebellar abnormalities, mild cerebellar vermis hypoplasia, elongated superior cerebellar peduncles, deepened interpeduncular fossa (molar tooth sign), polymicrogyria, dysmorphic features (hypertelorism, broad and depressed nasal bridge, frontal bossing), macrocephaly, global macrosomia, tall stature (in Italian family), oculomotor apraxia, ataxia, dysarthria, nystagmus (in Egyptian family), postaxial polydactyly, abnormal EEG (in one patient).", "TAKENOUCHI-KOSAKI SYNDROME": "Clinical features of the rare genetic disorder described in the texts include: persistent ductus arteriosus, inguinal hernia, developmental delay, lymphedema, thrombocytopenia, midface hypoplasia, synophrys, ptosis, exotropia, short philtrum, thin upper lip, poor visual acuity, congenital nystagmus, sensorineural deafness, retinal dysplasia, pericardial effusion, hydrothorax, ascites, hypoalbuminemia, protein-losing enteropathy, poor postnatal growth, microcephaly, delayed psychomotor development, intellectual disability, behavioral disorders, facial dysmorphism, hearing and vision problems, cardiac abnormalities, immune and hematologic involvement, skeletal anomalies, genitourinary abnormalities, hypotonia, skin nevi, seizures, and brain abnormalities.", "AL KAISSI SYNDROME": "Rare genetic disorder: Congenital developmental disorder with multiple clinical features. Patients present with intrauterine growth retardation, severe hypotonia, and dysmorphic facial features. Poor overall growth, delayed development, and moderate to severe intellectual disability. Cervical spine anomalies, sacral dimple, and dysmorphic facial features (synophrys, hypertelorism, etc.) are common. Small hands with deep palmar creases, joint hyperlaxity, and pes planus may be present. Thin corpus callosum observed in some patients. Atrial septal defects seen in two patients.", "LENZ-MAJEWSKI HYPEROSTOTIC DWARFISM": "Clinical features of the rare genetic disorder include:\n- Multiple congenital anomalies (delayed closure of fontanels, proximal symphalangism, prominent cutaneous veins)\n- Mental retardation\n- Progressive skeletal sclerosis with severe growth retardation\n- Progeroid appearance\n- Dysplastic dental enamel\n- Skin hypoplasia and joint laxity suggesting a connective tissue disorder\n- Choanal atresia\n- Loose and wrinkled atrophic skin with short digits and partial syndactyly\n- Nasal 'snorting' and nasolacrimal duct obstruction\n- Defective enamel in erupting teeth\n- Radiologic features of progressive sclerosis of the skull, facial bones, and vertebrae, broad clavicles and ribs, and skeletal undermodeling\n- Shortening of fingers and metacarpals, loose thin skin with hyperlaxity, hyperostosis of the iliac wings, and humeroradial synostosis\n- Enlarged fontanel, hypertelorism, macrostomia, high palate, short yellow carious teeth, and progeroid appearance\n- Short neck, limited elbow extension, brachydactyly, cutaneous syndactyly, stiff finger joints, and hyperconvex nails\n- Hip dysplasia, synostosis of metacarpals, and kyphoscoliosis\n- Thick lips and tongue, short teeth, enlarged mandible, weak and atrophic skin, and prominent veins\n- Massive thickening of long tubular bones, proximal synostosis of metacarpals, and proximal symphalangism of fingers\n- Dysgenesis of the corpus callosum, cleft palate, and hydrocephalus in some cases\n- Mild mental retardation, cutis laxa, progeroid facial appearance, and skeletal changes including calvarial hyperostosis and sclerosis\n- Short stature, microcephaly, and intellectual disability\n- Dental enamel hypoplasia, macroglossia, and choanal atresia in some cases\n- Radiographic abnormalities of skull and vertebral sclerosis, diaphyseal hyperostosis, and undermodeling, broad clavicle and ribs\n- Cortical atrophy, hydrocephalus, and pituitary hypoplasia in some cases\n- Cryptorchidism in some cases", "FONTAINE PROGEROID SYNDROME": "Clinical features of the rare genetic disorder include pre- and postnatal growth retardation, diminished subcutaneous fat, wrinkled skin, scant hair growth, hypoplastic distal phalanges with hypoplastic nails, umbilical hernia, large open anterior fontanel, and normal cognitive and motor development. Patients may have a prematurely aged appearance since birth. Some patients may also exhibit natal teeth, large hands and feet with long, tapering digits, developmental delay, and neurologic impairment. Severe prenatal forms of the disorder may present with marked intrauterine growth retardation, absence of subcutaneous fat, brachydactyly, absent nipples, hypoplastic external genitalia, abnormal ear lobes, and premature aging. Other features may include craniosynostosis, anonychia, extensive abdominal muscle hypoplasia, dental anomalies, and hypoplasia of the labia majora. The disorder is associated with high mortality rates in infancy.", "OMODYSPLASIA 2": "Omodysplasia is a rare genetic disorder characterized by facial anomalies (depressed nasal bridge, broad base of the nose, long philtrum) and skeletal abnormalities such as short humeri, hypoplastic everted condyle, proximal radioulnar diastasis, and anterolateral dislocation of the head of the radius. Other features include micromelic dwarfism, shallow olecranon fossae, shortened first metacarpals, small laterally displaced patellas, large forehead, hypertelorism, maxillary hypoplasia, and hypoplastic genitalia. Intellectual and motor development are typically normal. Additional findings may include short stature, prominent forehead, flat face, rhizomelic shortening of extremities, inability to pronate and supinate forearms, dental crowding, coxa valga, bicornuate uterus, low-set posteriorly angulated ears, downslanting palpebral fissures, upturned short nose, and short thumbs.", "CONGENITAL HEART DEFECTS, DYSMORPHIC FACIAL FEATURES, AND INTELLECTUAL DEVELOPMENTAL DISORDER": "Clinical features of the rare genetic disorder include atrial and/or ventricular septal congenital heart defects, pulmonary valve abnormalities, recognizable facial gestalt (hypertelorism, upslanted palpebral fissures, epicanthal folds, ptosis, strabismus, posteriorly rotated ears, thin upper lip, small mouth), global developmental delay, delayed walking and speech acquisition, intellectual disability, seizures, mild microcephaly, feeding difficulties, agenesis of the corpus callosum, aplasia of the inferior half of the cerebellar vermis, small cerebral cortex, periventricular leukomalacia, clinodactyly and/or camptodactyly of the fingers, hypotonia, joint hypermobility, and spasticity. Additional features include learning disabilities, autistic features, poor growth, short upslanting palpebral fissures, telecanthus or hypertelorism, epicanthal folds, low-set or posteriorly rotated ears, curly hair, digital anomalies (clinodactyly, prominent fetal pads), structural cardiac anomalies, and seizures.", "COFFIN-SIRIS SYNDROME 7": "Patients with this rare genetic disorder, known as CSS, exhibit global developmental delay, intellectual disability, delayed speech and walking, and hypoplasia of the fifth toenail. They also have coarse facial features, sparse scalp hair, downslanting palpebral fissures, and other dysmorphic features. Additional characteristics include feeding difficulties, poor growth, hearing impairment, behavioral abnormalities, and constipation. Some patients may have congenital heart defects or craniosynostosis. Brain imaging may show mild abnormalities, but not of the corpus callosum.", "DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 66": "DEE66 is a rare genetic disorder characterized by early-onset seizures, including focal motor, autonomic, tonic, and generalized tonic-clonic seizures. Patients may also experience myoclonic seizures. Developmental delay, intellectual disability, delayed speech, and behavioral disturbances are common. Neurologic features include hypotonia, hand stereotypies, wide-based gait, hyperreflexia, nystagmus, myopia, and cortical visual impairment. Dysmorphic facial features may include coarse features, synophrys, hypertelorism, downslanting palpebral fissures, broad nasal root, thin upper lip, and wide mouth with downturned corners. Other features may include distal limb anomalies, cardiac septal defects, cryptorchidism, and hematologic disturbances. Brain MRI may show dysgenesis of the cerebellar folia, inferior vermian hypoplasia, mega cisterna magna, and hypothalamic fusion in some cases.", "MICROCEPHALY, GROWTH RESTRICTION, AND INCREASED SISTER CHROMATID EXCHANGE 2": "Patients with this rare genetic disorder exhibit growth failure, intrauterine growth retardation, low birth growth parameters, and poor postnatal growth. They also have microcephaly, multiple cafe-au-lait patches, and some may have dilated cardiomyopathy. Other features include mild developmental delay, decreased subcutaneous fat, recurrent infections, and gastroesophageal reflux. Dysmorphic facial features, such as frontal bossing and progeroid features, may be present. Skeletal muscle biopsy showed mitochondrial DNA depletion in one patient. No malignancies were reported, but the patients were still young at the time of the study.", "MAB21L2": "Rare genetic disorder: mutations in MAB21L2 gene. Clinical features include microphthalmia with coloboma or anophthalmia, rhizomelic skeletal dysplasia, joint contractures, hypoplastic femoral condyles, pes cavus, hypospadias, calf muscle wasting, macrocephaly, precocious puberty, intellectual disability, autistic spectrum disorder, blindness, skeletal dysmorphism, dislocations, syndactyly, facial dysmorphism, strabismus, shortening of long bones, cataracts, corectopia, nystagmus.", "INTELLECTUAL DEVELOPMENTAL DISORDER WITH HYPERTELORISM AND DISTINCTIVE FACIES": "Phenotype: Intellectual impairment, delayed motor skills and speech, dysmorphic features (high hairline, hypertelorism, abnormal palpebral fissures, thin eyebrows, low-set posteriorly rotated ears, broad nasal bridge and tip, thin upper lip, narrow jaw), generalized overgrowth, macrocephaly, tapered fingers, flat feet, fifth finger clinodactyly.", "KCTD3": "Rare genetic disorder: developmental epileptic encephalopathy with global developmental delay, central hypotonia, progressive peripheral hypertonia, variable dysmorphic facial features, posterior fossa abnormalities (Dandy-Walker malformation to isolated hypoplasia of the cerebellar vermis), hydrocephalus, abnormal brain myelination, and multicystic kidney.", "SKIN CREASES, CONGENITAL SYMMETRIC CIRCUMFERENTIAL, 1": "Clinical features of the rare genetic disorder include:\n- Multiple benign ring-shaped skin creases on extremities, fingers, toes, and trunk\n- Facial dysmorphism such as epicanthal folds, upslanting palpebral fissures, hypertelorism, and median cleft palate\n- Neuroblastoma in some cases\n- Mental retardation and motor retardation\n- Recurrent febrile seizures\n- Congenital heart defects in some cases\n- Smooth muscle hamartoma and fragmented elastic fibers in skin biopsies\n- Other associated anomalies such as craniofacial anomalies, cleft palate, hypoplastic scrotum, inguinal and umbilical hernias, microphthalmia, microcornea, microcephaly, hearing impairment, undescended testes, short stature, and psychomotor developmental delay.", "NR2F1": "Clinical features of the rare genetic disorder include optic nerve atrophy, developmental delay, impaired intellectual development, decreased visual acuity, visual field defects, variable optic disc abnormalities, cerebral visual impairment, ocular anomalies (strabismus, latent nystagmus), dysmorphic features (protruding ears, small nasal ridge, high nasal bridge, etc.), hypotonia, obsessive-compulsive disorder, autistic features, impaired intellectual development, oromotor dysfunction, repetitive behavior, seizures, attention deficit-hyperactivity disorder, hearing defect, spasticity, vomiting, impaired consciousness, myopathic signs, thin corpus callosum, delayed motor development, borderline intellectual development, retrognathia, external ear protrusion, hyperbilirubinemia, pervasive developmental disorder, nonverbal learning disability, generalized joint hyperextensibility, optic nerve hypoplasia, joint hyperextensibility, conductive hearing loss, cervicothoracic syringomyelia, macrocephaly, broad forehead, speech delay, vision impairment, alacrima, cortical visual impairment, love of music, high pain tolerance, sleep difficulties, touch sensitivity, congenital disorder of glycosylation type 1c, protein-losing enteropathy, ataxia.", "SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 23": "Text 1: Three brothers with intellectual disability, epilepsy, and ataxia. Seizures remitted but recurred and were difficult to control. Moderate to severe intellectual disability, severe ataxia, dysmorphic features, and large hands.\n\nText 2: A 6-year-old boy with developmental delay, microcephaly, failure to thrive, and ataxic gait. Seizures, hypotonia, neutropenia, cardiac arrhythmia, hyponatremia, and gastric dysmotility. Severe reduction in muscle activity and high lactate/pyruvate ratio. Improvement with treatment.", "SOTOS SYNDROME 2": "Abnormality of the cardiovascular system Flushing Broad forehead Seizure Dolichocephaly Autistic behavior Downslanted palpebral fissures Global developmental delay Scoliosis Long face Ventriculomegaly Abnormality of the kidney Accelerated skeletal maturation Abnormal mandible morphology Sparse anterior scalp hair Soft, doughy skin Overgrowth", "MARSHALL-SMITH SYNDROME": "Marshall-Smith syndrome is a rare genetic disorder characterized by accelerated skeletal maturation, failure to thrive, dysmorphic facial features, osseous fragility, and respiratory complications. Patients may exhibit osteopenia, fractures, blue sclerae, and prominent eyes. Muscle abnormalities, gait problems, and connective tissue manifestations are also observed. Long-term survival is possible with aggressive management of respiratory problems. Developmental delay, unusual behavior, short stature, kyphoscoliosis, and characteristic facial features are common. Mortality from respiratory complications is high, but airway support has improved survival into adulthood.", "VERHEIJ SYNDROME": "Chromosome 8q24.3 Deletion Syndrome: Delayed development, poor growth, seizures, congenital heart defects, polydactyly, dysmorphic facial features, laryngotracheomalacia, hypoplastic corpus callosum, delayed myelination, cerebral atrophy, and renal abnormalities. PUF60 Mutations: Growth retardation, delayed development, microcephaly, dysmorphic facial features, seizures, congenital heart defects, joint laxity/dislocation, vertebral anomalies, ocular colobomas, renal anomalies, feeding difficulties, and branchial arch defects. Phenotypic variability observed.", "PURA": "Rare genetic disorder characterized by:\n- Neonatal hypotonia\n- Severely delayed psychomotor development\n- Early-onset feeding difficulties\n- Significant respiratory insufficiency\n- Early-onset seizures (often myoclonic)\n- Abnormal EEG pattern\n- Dysmorphic facial features (variable)\n- Myopathic facies (open mouth, high-arched palate)\n- Nystagmus and strabismus\n- Hypomyelination or delayed myelination on brain imaging\n- Nonverbal and nonambulatory\n- Phenotypic overlap with chromosome 5q31.3 microdeletion syndrome\n- Endocrine abnormalities may be present\n- Global developmental delay\n- Limited vocabulary or nonverbal\n- Variable dysmorphic features\n- Brain imaging abnormalities (delayed myelination, ventriculomegaly, etc.)\n- Cerebellar vermis hypoplasia and other brain abnormalities\n- Reduced expression of GLUT1 in red blood cells\n- Cardiac abnormalities (hypertrophic myocardiopathy)\n- Hiccups in utero\n- Neonatal problems (hypotonia, feeding difficulties, respiratory insufficiency)\n- Hypersomnolence, hypothermia, exaggerated startle response\n- Severe developmental delay, poor speech\n- Abnormal gait and movement\n- Seizures (refractory in some cases)\n- Visual problems (strabismus, nystagmus, cortical visual impairment)\n- Scoliosis, hip dysplasia, joint hyperlaxity\n- Dysmorphic facial features (hypotonic facies, high anterior hairline, etc.)\n- Systemic involvement (cardiac defects, constipation, etc.)\n- Point mutations or larger deletions in the PURA gene\n- Decreased cerebral volume and delayed myelination on brain imaging\n- Distinctive facial features (tented upper lip vermilion, long philtrum, etc.)\n- Primary amenorrhea in some cases.", "KCNJ6": "Clinical features of this rare genetic disorder include severe developmental delay, distinct facial appearance with tightly adherent skin, generalized lipodystrophy, small pinched nose, poor postnatal growth, failure to thrive, self-mutilation and chewing of the tongue and lips, opisthotonic posturing and febrile seizures, decreased facial subcutaneous fat, large prominent eyes, tented upper lip, high-arched palate, hypertonia, hyperreflexia, wrinkled forehead and chin skin, absence of subcutaneous tissue, protruding nasal tip, narrow and high-arched palate, micrognathia, flexion contractures, scoliosis, and respiratory insufficiency.", "WIEDEMANN-RAUTENSTRAUCH SYNDROME": "Clinical features of the rare genetic disorder, Wiedemann-Rautenstrauch syndrome (WDRTS), include neonatal progeroid appearance, severe growth deficiency, absence of subcutaneous fat with fat accumulation in specific areas, sparse hair, ectropion, pseudohydrocephaly, wide open cranial sutures, beaking of the nose, delayed closure of fontanels, lipoatrophy, hypoplastic facial bones, thin long bones, cognitive impairment, and variable life expectancy. Other reported features include congenital heart defects, urinary reflux, hypothyroidism, laryngomalacia, camptodactyly, recurrent skin infections, gynecomastia, galactorrhea, cryptorchidism, hypospadias, scoliosis, and renal abnormalities. Phenotypic variability and possible involvement of bone maturation, lipid, and hormone metabolism are suggested.", "POLR2A": "Patients with this rare genetic disorder exhibit a range of neurodevelopmental symptoms, including global developmental delay, hypotonia, delayed walking, speech and language delay, strabismus, and behavioral abnormalities. Some patients have a severe phenotype with additional features such as feeding difficulties, recurrent respiratory tract infections, microcephaly, and seizures. Others have a milder form of the disorder with less severe or absent symptoms. Brain imaging abnormalities, such as delayed myelination and cerebellar atrophy, are common in most patients.", "RALA": "Patients with the rare genetic disorder associated with RALA gene mutations exhibit neurodevelopmental delays, hypotonia, delayed walking or inability to walk, and impaired intellectual development. They may have feeding difficulties, seizures, autism spectrum disorder, and behavioral abnormalities. Dysmorphic facial features include macrocephaly or microcephaly, broad forehead, narrow midface, and various eye abnormalities. Other features include skeletal anomalies and distal skeletal abnormalities. Brain imaging may show abnormalities such as thin corpus callosum or polymicrogyria. Another patient with the disorder exhibited similar characteristics, including global developmental delay, hypotonia, impaired intellectual development, and dysmorphic facial features. This patient also had aggressive behavior and normal brain imaging.", "INTELLECTUAL DEVELOPMENTAL DISORDER WITH CARDIAC DEFECTS AND DYSMORPHIC FACIES": "Rare genetic disorder: Syndromic neurodevelopmental disorder with various clinical features. Patients have global developmental delay, impaired intellectual development, learning disabilities, speech delay, and delayed walking. Most patients have congenital heart defects. Dysmorphic features include triangular face, short nose, deep-set eyes, and highly arched eyebrows. Some patients have skeletal anomalies, seizures, pectus abnormalities, and feeding/respiratory difficulties. Brain imaging shows nonspecific abnormalities. Prenatal features include skin edema, hydrothorax, polyhydramnios, thick nuchal fold, micrognathia, clenched hands, and abdominal cyst.", "TURNPENNY-FRY SYNDROME": "Patients with this rare genetic disorder exhibit impaired intellectual development, distinctive facial features (such as broad forehead, sparse hair, and malar hypoplasia), and impaired growth. They may also have dysplastic ears, facial hypotonia, feeding difficulties, constipation, cardiovascular anomalies, skeletal anomalies, and variable head size. Additionally, they commonly experience delayed speech and may have MRI abnormalities.", "MACROCEPHALY, ACQUIRED, WITH IMPAIRED INTELLECTUAL DEVELOPMENT": "Rare genetic disorder: Macrocephaly, impaired intellectual development, speech delay, mild impaired intellectual development, motor delays, muscular hypotonia, behavioral and psychiatric abnormalities, no seizures or neurologic deficits, thinning/hypoplasia/agenesis of corpus callosum, no ventriculomegaly, possible heterotopia/cerebellar tonsillar ectopia/diffuse cerebral atrophy/dorsal meningocele, normal vision and hearing, long face, high forehead, sparse eyebrows, downslanting palpebral fissures, mild blepharophimosis, narrow nasal bridge, anteverted nares, long and smooth philtrum, inconsistent features, de novo mutation (except one case).", "COLE-CARPENTER SYNDROME 1": "Rare genetic disorder resembling osteogenesis imperfecta (OI) with additional features: ocular proptosis, orbital craniosynostosis, hydrocephalus, distinctive facial features. Normal at birth, but recurrent fractures occurred before first birthday. Intellectual development unaffected. Inheritance unknown. Another case with failure to thrive, macrocephaly, proptosis, blue sclerae, micrognathia, small limbs, bowing of lower limbs, no fractures. Variant form of Cole-Carpenter syndrome. Severe case with hydrops fetalis, hypertelorism, hypoplastic orbits, brachydactyly, hydrocephalus, connective tissue signs. Another case with severe OI, craniosynostosis, growth failure, craniofacial abnormalities. Follow-up on two patients: wheelchair-bound, short stature, severe scoliosis, limb deformities, low bone density. Normal serum levels.", "ARCN1": "Clinical features of the rare genetic disorder caused by ARCN1 gene mutation include rhizomelic short stature, microcephaly, micrognathia, laxity of small joints, developmental delay, posterior cataract, cleft palate, ventricular septal defect (VSD), cryptorchidism, seizures, and autism. Other features observed include cardiomegaly, glycosylation deficiency, cleft uvula, muscular hypotonia, pectus carinatum, underdeveloped genitalia, distinctive facial features, spastic paraplegia, aspiration and swallowing dysfunction, intractable focal epilepsy, and global developmental delay. Commonly seen features also include intrauterine growth restriction (IUGR), preterm birth, liver dysfunction, genitourinary (GU) anomalies, and rhizomelic shortening of limbs. Complications such as Pierre-Robin sequence, liver enzyme elevations, glycosylation abnormalities, cataracts, and hepatoblastoma may occur. Intrafamilial variability suggests potential genetic modifiers or environmental effects influencing phenotypic severity.", "SCHAAF-YANG SYNDROME": "Clinical features of the rare genetic disorder described in the texts include:\n- Distal arthrogryposis (camptodactyly of fingers, hammertoes)\n- Hypopituitarism\n- Severe mental retardation\n- Facial anomalies (boxy head, square face, small tipped nose, chubby cheeks, micrognathia)\n- Growth hormone abnormalities\n- Developmental delay\n- Anterior pituitary dysfunction\n- Retinal coloboma\n- Laryngeal abnormalities\n- Aminoaciduria\n- Hypokalemia\n- Abnormal skeletal survey\n- Delayed myelination\n- Impaired intellectual development\n- Autism spectrum disorder\n- Feeding difficulties\n- Hypogonadism\n- Seizures\n- Short stature\n- Joint contractures\n- Sleep apnea\n- Dysmorphic facial features (such as large mouth, coarse features, almond-shaped palpebral fissures)\n- Constipation\n- Micropenis\n- Cryptorchidism\n- Scoliosis or kyphosis\n- Hypothyroidism\n- Amenorrhea\n- Elevated ghrelin levels\n- Central hypothyroidism\n- Myotonia\n- Cleft palate\n- Corpus callosum dysplasia or hypoplasia\n- Hypoplastic external genitalia\n- Tracheomalacia or velopharyngeal insufficiency\n- Hypoglycemia\n- Chronic constipation\n- Gastroesophageal reflux\n- Temperature instability\n- Intellectual disability\n- Seizures\n- Digestive issues\n- Exaggerated kyphosis\n- Maternally imprinted, paternally expressed disorder\n- Arthrogryposis multiplex congenita (AMC)\n- Polyhydramnios\n- Decreased fetal movements\n- Clubfoot\n- Hypertelorism\n- Short palpebral fissures\n- Microretrognathia\n- Short neck\n- Fetal akinesia\n- Overlapping digits\n- Rocker-bottom feet\n- Gnathopalatoschisis", "FOCAL DERMAL HYPOPLASIA": "Clinical features of focal dermal hypoplasia (FDH) include congenital linear areas of thinning skin, herniations of adipose tissue (yellowish papules), cleft palate, syndactyly, polydactyly, nail and tooth deformities, ocular anomalies, sparse hair, apocrine gland anomalies, hydrocystomas, fibrovascular papillomas, laryngeal and esophageal papillomas, osteopathia striata, lobster-claw hand and foot deformities, telangiectases, preauricular sinuses, omphalocele, duodenal atresia, cardiac anomalies, oblique facial cleft, papillomatosis of the hypopharynx and larynx, facial clefting, and aplasia cutis congenita. Some cases may also have chromosomal abnormalities, giant cell tumors of bone, and corneal opacifications. FDH is associated with mutations in the PORCN gene and can have variable expressivity and lethality in males.", "GLASS SYNDROME": "Clinical features of the rare genetic disorder include severe mental retardation, microcephaly, craniofacial dysmorphism, cleft palate, seizures, and abnormal skin pigmentation. Other common characteristics are growth retardation, thin and sparse hair, feeding difficulties, hernia, broad-based gait, and tooth anomalies. Behavioral abnormalities such as hyperactivity, aggression, and sleeping problems are also observed. The disorder is associated with interstitial deletions of chromosome 2q32-q33, specifically affecting the SATB2 gene.", "ACROFACIAL DYSOSTOSIS 1, NAGER TYPE": "Nager acrofacial dysostosis is characterized by limb deformities such as absence of radius, radioulnar synostosis, and thumb hypoplasia. Mandibulofacial dysostosis is characterized by severe micrognathia and malar hypoplasia. Other features include ptosis of lower lids, hypoplasia of lower lid eyelashes, and cartilaginous pegs between antitragus and lobule. Some cases also involve cleft lip and palate, Hirschsprung disease, and cardiac malformations. Proximal radioulnar synostosis and foot anomalies are common. It is distinct from Miller acrofacial syndrome and split-hand deformity with mandibulofacial dysostosis.", "CEREBROCOSTOMANDIBULAR SYNDROME": "Clinical features of this rare genetic disorder, known as cerebrocostomandibular syndrome (CCMS), include mental retardation, palatal defects (short hard palate, absent soft palate, absent uvula), micrognathia, glossoptosis, severe costovertebral abnormalities, and gaps in the posterior portion of the ribs. Other common manifestations include neonatal respiratory distress, intrauterine and postnatal growth retardation, cleft palate, and microcephaly. Autosomal recessive and dominant inheritance patterns have been observed. Additional findings may include spina bifida, Pierre-Robin anomalad, cerebral involvement, and defects of the heart and kidneys. Radiologic findings include narrow thorax, abnormal rib gaps, and abnormal costotransverse articulation.", "ZTTK SYNDROME": "Phenotype characteristics of the rare genetic disorder include developmental delay, seizures, minor dysmorphisms, macrocephaly, brain white matter abnormalities, intestinal atresia, ventriculoseptal defect, postnatal growth retardation, relative macrocephaly, infantile hypotonia, severe intellectual disability, congenital heart disease, long slender extremities with hyperextensible joints, smooth velvety skin, distinctive facial features, visual problems, neonatal feeding difficulties, dysmorphic facial features, midface retraction, low-set ears, downslanting palpebral fissures, deep-set eyes, horizontal eyebrows, broad and/or depressed nasal bridge, short philtrum, brain abnormalities, short stature, musculoskeletal abnormalities, variable congenital malformations, poor feeding, respiratory difficulties, frontal bossing, bitemporal narrowing, thin corpus callosum, decreased levels of IgA and/or IgG, coagulation abnormalities, joint laxity, arachnodactyly, abnormal brain imaging, impaired intellectual development, preterm birth, small head circumference, neurologic abnormalities, behavioral problems, sleep disturbance, autism, gastrointestinal abnormalities, cardiovascular abnormalities, urogenital system abnormalities, visual impairment, hearing impairment, immune system abnormalities, endocrine issues, and hypertension.", "MENKE-HENNEKAM SYNDROME 1": "Patients with mutations in CREBBP (exon 30 or 31) exhibit a phenotype distinct from Rubinstein-Taybi syndrome (RSTS1). They do not have broad thumbs or characteristic facial features. However, they commonly experience developmental delay or intellectual disability, short stature, microcephaly, and variable facial characteristics such as short palpebral fissures, telecanthus, depressed nasal bridge, short nose, anteverted nares, short columella, and long philtrum. Autistic behavior and self-injurious behavior are observed in some cases. Other symptoms include recurrent upper airway infections, feeding problems, and impaired hearing. No major malformations are reported. Additional patients with MKHK1 also exhibit impaired intellectual development, autistic behavior, short stature, microcephaly, feeding problems, and vision and hearing impairment. Malformations such as cleft palate, congenital heart anomaly, renal anomaly, malrotation, and cryptorchidism are less common. Cerebral anomalies are seen in some patients, and facial features vary, but patients with mutations in a restricted 3-prime region resemble each other. Broad thumbs or angulated thumbs are not observed in any patients.", "MENKE-HENNEKAM SYNDROME 2": "Clinical features of the rare genetic disorder described in the texts include: \n- Floppy muscles and lax joints\n- Feeding difficulties, including difficulty swallowing\n- Recurrent otitis media, airway infections, and urinary tract infections\n- Low immunoglobulin levels\n- Strabismus and bilateral moderate sensorineural hearing loss\n- Duodenal ulcers suggestive of Crohn's disease\n- Autism spectrum disorder, with hyperactive behaviors and insomnia\n- Motor and speech delay, with walking achieved at 2.5 years and speech at age 5\n- Unusual sleep patterns and lack of hunger awareness\n- Speech delay and swallowing problems requiring therapy\n- Delay in fine motor skills\n- Average size and head circumference\n- Fibular deviation of large halluces in one patient\n- Progressive contracture of fifth fingers in one patient", "ZIMMERMANN-LABAND SYNDROME 3": "Zimmermann-Laband syndrome: mild to moderate intellectual disability, long and coarse face with bulbous nose, marked gingival enlargement, hypoplasia of distal phalanges of fingers and toes, hypoplasia or aplasia of fingernails and toenails, moderate hypertrichosis, coarse facial features, developmental delay, hypotonia, short distal phalanges, and patent ductus arteriosus.", "INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC, BILLUART TYPE": "Clinical features of the rare genetic disorder include X-linked mental retardation, neonatal hypotonia with motor delay, marked strabismus, early-onset complex partial seizures, moderate to severe mental retardation, cerebellar dysgenesis, cerebral corticosubcortical atrophy, subtle facial dysmorphism, cerebellar anomalies (hypoplasia, expansion of cisterna magna, retrocerebellar cysts), enlargement of lateral ventricles, hypogenitalism with cryptorchidism, microphallus, facial dysmorphism (long face, prominent forehead, deep-set eyes, infraorbital creases, short or upturned philtrum, large ears), hypoplasia of cerebellar vermis, cystic dilatation of cisterna magna, ventricular dilatation, global reduction of cerebral volume, autistic features, dysmorphic facial features (long semi-triangular face, deep-set eyes, broad high nasal root, peaked prominent nose, prominent chin), cerebellar signs (mild ataxia, intention tremor), ventriculomegaly, mild cognitive delay, speech impairment, attention-deficit hyperactivity disorder, and seizures.", "DIETS-JONGMANS SYNDROME": "This rare genetic disorder is characterized by mild to moderate intellectual impairment, a recognizable facial gestalt including long ears, broad nasal tip, thin upper vermilion, wide mouth, and prominent or pointed chin. Nonneutral palpebral fissures, behavioral problems (including ADHD and autism), short stature, neonatal feeding difficulties, epilepsy, hearing loss, and childhood hypotonia are also common. Some patients have additional medical conditions such as cancer, congenital hypothyroidism, hip dysplasia, hernias, cryptorchidism, diaphragmatic hernia, heterotaxy, strabismus, and visual impairments.", "OROFACIODIGITAL SYNDROME VI": "Rare genetic disorder: reduplicated big toes, hexadactyly, cleft lip/palate, lingual nodule, somatic and psychomotor retardation, absent olfactory bulbs and tracts, cryptorchidism, inguinal hernia, congenital heart disease, short stature, tachypnea, hyperpnea, normal intelligence in some cases, metopic ridge, accessory fold in ear, hypothalamic dysfunction, hypothalamic hamartoma, absence of pituitary gland, facial abnormalities, polydactyly, renal disease, delayed psychomotor development, mental retardation, ataxia, poor speech, cerebellar malformations, molar tooth sign, TMEM107 gene mutation, cerebellar vermis hypoplasia, tongue hamartoma, upper lip notch, intellectual disability.", "INTRAUTERINE GROWTH RETARDATION, METAPHYSEAL DYSPLASIA, ADRENAL HYPOPLASIA CONGENITA, GENITAL ANOMALIES, AND IMMUNODEFICIENCY": "Clinical features of the rare genetic disorder include adrenal hypoplasia congenita (AHC), intrauterine growth retardation (IUGR), dysmorphic facial features (small low-set ears, micrognathia), genitourinary abnormalities (bilateral cryptorchidism, micropenis, hypospadias), skeletal abnormalities (gracile long bones, metaphyseal cupping, osteopenia), and immunodeficiency (lymphocyte subset deficiencies, IgM hypogammaglobulinemia). Patients also exhibit limited energy, increased skin pigmentation, and respiratory tract infections can be fatal.", "COFFIN-SIRIS SYNDROME 8": "Clinical features of the rare genetic disorder include failure to thrive, benign hydrocephalus, speech delay, hypotonia, elevated lactate and ammonia, vitiligo, developmental delay, impaired intellectual development, delayed speech and language development, short stature, abnormalities of the mouth and nose, skeletal abnormalities, hypertrichosis and synophrys, sleep disturbances, seizures, behavioral abnormalities, dysmorphism, white matter lesions, thinning of the corpus callosum, cerebral atrophy, hypomyelination, fifth finger or toenail anomalies, scoliosis, cardiovascular abnormalities, and dysmorphic craniofacial features such as hypertrichosis, thick eyebrows, thin upper or thick lower lip vermilion, and upturned nose.", "NEURODEVELOPMENTAL DISORDER WITH DYSMORPHIC FACIES AND DISTAL SKELETAL ANOMALIES": "Patients with mutations in the ZMIZ1 gene exhibit a neurodevelopmental disorder characterized by global developmental delay, variable intellectual disability, delayed walking and speech, behavioral abnormalities (such as autism spectrum disorder, ADHD, and aggression), craniofacial abnormalities (including facial hypotonia, midface hypoplasia, and various eye, nose, and mouth abnormalities), hearing loss, ocular anomalies, joint hypermobility, hand and foot anomalies, mild congenital cardiac or urogenital malformations, and in some cases, seizures and brain abnormalities.", "NDST1": "Nonsyndromic intellectual disability with delayed psychomotor development, absent expressive speech, hypotonia, therapy-responsive seizures, aggression, self-injurious behavior, and sleep disturbances.", "NFIA": "BRMUTD: Failure to thrive, jaundice, abnormal craniofacial features, delayed psychomotor development, hypotonia, articulation difficulties, neuropsychologic problems, brain malformations, urinary involvement, macrocephaly, craniosynostosis, developmental delay, dysmorphic features. Chromosome 1p32-p31 Deletion Syndrome: Hypoplastic corpus callosum, hydrocephalus/ventriculomegaly, developmental delay, tethered spinal cord, Chiari type I malformation, seizures, urinary tract defects, pigmentary retinopathy, skeletal abnormalities. Chromosome 1p32 Deletion Syndrome: Muscular hypotonia, macrocephaly, hypoplasia of corpus callosum, ventriculomegaly, dysmorphic features. Chromosome 1p32 Deletion Syndrome (follow-up): Delayed developmental milestones, cognitive impairment, craniofacial anomalies, ocular hypertension, sleep difficulties, hypertonia, intracerebral aneurysm. Chromosome 1p32-p31 Deletion Syndrome: Macrocephaly, brain anomalies, dysmorphic features, developmental and motor delay, craniofacial asymmetry, hypoplastic corpus callosum, ventriculomegaly, polymicrogyria, arachnoid cysts.", "COFFIN-SIRIS SYNDROME 10": "Clinical features of the rare genetic disorder described in Zawerton et al (2019) include global developmental delay, mild to severe intellectual disability, facial dysmorphism (anteverted nares, wide mouth with cupid bow, posteriorly rotated ears), and fifth finger clinodactyly. Other characteristics include growth abnormalities, seizures, hypotonia, ventricular septal defect, feeding difficulties, and constipation.\n\nIn Angelozzi et al (2022), patients with mutations in the SOX4 gene exhibited a syndromic neurodevelopmental disorder with hypotonia, borderline to mild intellectual disability, behavioral issues, speech delay, and motor delay. Dysmorphic features included a tall forehead, epicanthal folds, and a wide mouth with full lips. Other findings included palatal anomalies, retrognathia, cardiac defects, visual impairment, and occasional hearing impairment. Specific features of Coffin-Siris syndrome were not present.", "PEPD": "Clinical features of prolidase deficiency include excretion of massive amounts of glycyl-L-proline and other di- and tri-peptides containing proline, dry and cracked erythematous palms and soles, obesity from an early age, mild mental retardation, mild diffuse demineralization of long bones, chronic dermatitis, frequent infections, splenomegaly, massive imidodipeptiduria, chronic ear and sinus infections, chronic skin lesions, distinctive clinical features of recurrent skin ulceration, lymphedema, hepatosplenomegaly, severe leg ulcers, variable severity of mental retardation, unusual facial appearance, disturbance of complement component C1q, unusual facial appearance, erosive cystitis, systemic lupus erythematosus (SLE), developmental delay, facial dysmorphism, ocular hypertelorism, exophthalmos, upward or downward slanting palpebral fissures, small-beaked nose, low posterior hairline, facial hirsutism, slender upper lip, dermatologic manifestations, splenomegaly, hepatitis-like symptoms, osteomyelitis, recurrent lung infections, asthma, chronic lung disease resembling cystic fibrosis (CF), and great inter- and intrafamilial variability.", "DEVELOPMENTAL DELAY WITH OR WITHOUT DYSMORPHIC FACIES AND AUTISM": "Patients with this rare genetic disorder exhibit global developmental delay, impaired intellectual development, speech delay or absence, delayed walking, dysmorphic facial features (such as hyper- or hypotelorism, upslanting palpebral fissures, and micrognathia), microcephaly, short stature, cleft lip/palate, hypotonia, feeding difficulties, visual and hearing impairments, brain abnormalities (including cerebellar vermis hypoplasia and cortical atrophy), cardiac anomalies (such as ventricular septal defects and patent ductus arteriosus), renal or genital malformations, and other anomalies (such as dysplastic nails and laryngotracheomalacia). Clinical variability exists, with some patients having a less severe phenotype characterized by global developmental delay, mildly impaired intellectual development, speech delay, dysmorphic features, and normal brain imaging. Another case report described a patient with obsessive-compulsive disorder, paranoia, and auditory hallucinations, who had above average intelligence and a missense mutation in the TRRAP gene.", "RAC3": "Text 1: Girl with global developmental delay, poor language, seizures, thin corpus callosum. Dysmorphic features: midface hypoplasia, micrognathia, hypertelorism, long eyelashes, prominent eyes, anteverted nares, broad nasal bridge, short nose, long philtrum, dental anomalies. Clinodactyly, fetal finger and toe pads, genital hypoplasia. Resembles Robinow syndrome.\n\nText 2: 5 patients with neurodevelopmental disorder. Global developmental delay, severely to profoundly impaired intellectual development, abnormal muscle tone. Seizures in 2 patients, scoliosis in 3 patients. Brain imaging shows variable structural abnormalities, including absence/thin corpus callosum, enlarged ventricles, cerebral dysgenesis with polymicrogyria and heterotopia. Dysmorphic features: frontal bossing, brachycephaly, prominent glabella, hypertelorism, narrow palpebral fissures, high-arched eyebrows, depressed nasal bridge, short philtrum, high-arched palate, dental crowding, simple ears, full lips, tapered fingers, clinodactyly.\n\nText 3: 10 patients with NEDBAF. Neurologic findings: hypotonia, seizures, dyspraxia, spasticity. Microcephaly in 12.5%, abnormal head shape in 31.2%. Brain imaging abnormalities: corpus callosum abnormalities, global brain volume reduction, malformations of cortical development, cerebellar dysplasia, brainstem anomalies. Feeding difficulties common. Other features: respiratory issues, joint laxity, nystagmus.", "NOONAN SYNDROME 12": "Noonan syndrome with RRAS2 gene mutations. Facial gestalt, variable severity. Prenatal features in 5/6 probands, no pulmonary valve stenosis or hypertrophic cardiomyopathy.", "PIGB": "Developmental disorder with early-onset epilepsy, global developmental delay, severe intellectual impairment, hypotonia, feeding problems. Onset of seizures in first year of life, often refractory to treatment. Dysmorphic features, distal skeletal abnormalities, variable visual and hearing problems. Brain imaging abnormalities in half of patients. Increased serum alkaline phosphatase. Other variable abnormalities include polyhydramnios, premature birth, congenital heart defects. One family previously diagnosed with DOORS syndrome, with increased 2-oxoglutaric acid.", "RAB11B": "Clinical features of this rare genetic disorder include severely delayed psychomotor development, severe to profound intellectual disability with absent speech, hypotonia, delayed walking, ataxic gait, spasticity, dystonia, childhood-onset epilepsy (well-controlled in most cases), ophthalmologic abnormalities (nystagmus, hypermetropia, strabismus, optic atrophy/impaired vision), tapering fingers, hip dysplasia, pes cavus or clubfoot, skeletal anomalies (clinodactyly, overriding toes, simian crease), dysmorphic facial features (facial hypotonia, deep-set eyes, upslanting palpebral fissures, full upper eyelids, dysplastic ears), mild microcephaly, brain abnormalities (decreased cortical white matter, thin corpus callosum, decreased cerebellar white matter, enlarged ventricles, cerebellar vermis hypoplasia, thin brainstem, delayed myelination, optic nerve hypoplasia), severe disability, limited comprehension, simple tasks, behavior abnormalities (stereotypic behavior, bruxism, drooling, hand-flapping), and incontinence in some cases.", "GRID2": "Clinical features of the rare genetic disorder include cerebellar ataxia, nystagmus, hypotonia, delayed psychomotor development, unsteady gait, incoordination of gross motor movements, dysarthria, poor overall growth, oculomotor apraxia, pale optic disc, dysmetria, dysdiadochokinesis, pyramidal tract involvement, hyperreflexia, extensor plantar responses, intellectual disability, difficulty walking, occasional or persistent tonic upgaze, severely limited speech, and progressive and severe cerebellar atrophy. No seizures or dysmorphic features were observed.", "FBXO11": "Rare genetic disorder: \n- Syndromic intellectual developmental disorder \n- Delayed psychomotor development \n- Intellectual disability (ranging from mild to severe) \n- Delayed speech, some nonverbal \n- Mildly delayed walking \n- Seizures (in some patients) \n- Short stature \n- Strabismus, hypermetropia \n- Hypotonia \n- Sleeping difficulties \n- Distal mild skeletal anomalies \n- Behavioral abnormalities \n- Dysmorphic features \n- Small head circumference \n- Downslanting palpebral fissures \n- Hypertelorism \n- Low-set ears \n- Long philtrum \n- Narrow mouth \n- Everted lower lip \n- Long face \n- Impaired intellectual development \n- Behavioral problems (including autism spectrum disorder, ADHD, anxiety, aggression) \n- Hypotonia \n- Epilepsy (in some patients) \n- Enlarged ventricles (in some patients) \n- Obesity (in some patients) \n- Facial features: high broad forehead, long palpebral fissures, thin upper lip \n- Minor hand abnormalities \n- Gastrointestinal problems \n- Vision problems", "DESANTO-SHINAWI SYNDROME": "Rare genetic disorder: Global developmental delay, dysmorphic features (broad forehead, flat nasal bridge, hypertelorism, synophrys, strabismus), hypotonia, gastrointestinal difficulties (feeding, constipation), non-verbal or delayed language acquisition, behavioral abnormalities (aggression, anxiety, ADHD, autistic features), additional dysmorphic features (brachycephaly, deep-set eyes, rotated/simple ears, thin upper lip, downturned mouth, inverted nipples), myopia and astigmatism in three patients, sensorineural hearing loss in one patient.", "PRIMROSE SYNDROME": "Clinical features of Primrose syndrome include mental retardation, progressive wasting of distal muscles, calcification of pinnae, cataracts, recurrent otitis media, deafness, hard mass in the hard palate, joint contractures, sparse body hair, dysmorphic facial features, germ cell tumor, congenital heart disease, hip dysplasia, agenesis of the corpus callosum, distal muscle wasting, wheelchair dependence, spastic paraparesis, areflexia, motor tics, self-flagellating behaviors, basal ganglia calcification, increased serum calcitonin, macrocephaly, wide forehead, large ears, thoracic kyphosis, genu valgum, hearing loss, calcification of ear cartilages, left ventricular remodeling, hypogonadism, low bone density, disturbances of glucose metabolism, insulin-resistant diabetes, contractures, ectopic calcification of ears and brain, progressive neurologic signs, gait ataxia, pyramidal signs, cerebral calcification, peripheral neuropathy, dysmorphic facies, hypoplasia of corpus callosum, congenital hypothyroidism, hearing impairment, characteristic facial dysmorphology, short stature, large paranasal sinuses, narrow cranial base, maxillary hypoplasia, supernumerary tooth, retention of mandibular premolars, macrocephaly, subarachnoid spaces, hypoplastic corpus callosum, pituitary pars intermedia cyst, convergent strabismus, narrow forehead, underdeveloped supraorbital ridges, malar flattening, wide and depressed nasal bridge, ankle contractures, global developmental delay, muscular hypotonia, broad face and forehead, high anterior hairline, long ears, short palpebral fissures, diastema of upper central incisors, short hands, broadened thumbs, deep palmar creases, bilateral sandal gaps, and hypertrichosis.", "VAN MALDERGEM SYNDROME 2": "Van Maldergem syndrome-2 (VMLDS2) is a rare genetic disorder characterized by distinct facial features (large fontanels, maxillary hypoplasia, micrognathia, flat face, blepharophimosis, telecanthus, broad nasal bridge, and microtia), hearing loss, neonatal hypotonia, intellectual disability, poor growth, respiratory problems, skeletal abnormalities, small kidneys, and brain abnormalities (nodular periventricular heterotopia, dysmorphic corpus callosum, or agenesis of the corpus callosum). Other features may include seizures, talipes equinovarus, finger camptodactyly, joint laxity, dental malocclusion, genital abnormalities, and sacral dimple.", "HENNEKAM LYMPHANGIECTASIA-LYMPHEDEMA SYNDROME 2": "Rare genetic disorder: Hennekam lymphangiectasia-lymphedema syndrome.\nPhenotype characteristics: severe lymphedema of limbs, genitalia, and face, severe mental retardation, hypoproteinemia, hypogammaglobulinemia, lymphocytopenia, flat face, flat nasal bridge, hypertelorism, epicanthal folds, small mouth, tooth anomalies, ear defects, Oriental facial appearance, seizures, erysipelas, autosomal recessive inheritance, unusual facial appearance, blepharophimosis, small ears, irregular dentition, hearing loss, poor overall growth, microcephaly, lymphangiectasia affecting various organs, camptodactyly, syndactyly, cognitive impairment. Similar to Van Maldergem syndrome.", "HELSMOORTEL-VAN DER AA SYNDROME": "Rare genetic disorder: HVDAS\n- Impaired intellectual development, developmental delay, and severe intellectual disability\n- Autism spectrum disorder, attention deficit/hyperactivity disorder, anxiety disorder, and obsessive-compulsive behavior\n- Dysmorphic facial features: prominent forehead, high hairline, downslanting palpebral fissures, notched eyelids, broad nasal bridge, thin upper lip, and smooth philtrum\n- Other features: hypotonia, feeding problems, recurrent infections, short stature, joint laxity, hand abnormalities, seizures, and congenital heart defects\n- Visual problems: hypermetropia, cortical visual impairment, exotropia, amblyopia, and astigmatism\n- Genetic mutations in the ADNP gene, with additional features like cataract, microcephaly, muscular hypotonia, inverted nipples, sparse scalp hair, iris coloboma, joint hypermobility, hirsutism, depressed nasal bridge, thick lower lip vermilion, widely spaced teeth, plagiocephaly, obesity, inguinal hernia, cryptorchidism, low-set ears, microtia, broad thumb, and respiratory distress\n- Brain imaging abnormalities: wide ventricles, cerebral atrophy, underdevelopment of the corpus callosum, delayed myelination, white matter lesions, and cortical dysplasia\n- Other systemic involvement: structural cardiac abnormalities, urogenital abnormalities, joint hypermobility, and hand or foot abnormalities.", "PPP1R21": "Rare genetic disorder: Neurodevelopmental Disorder with Hypotonia, Facial Dysmorphism, and Brain Abnormalities (NEDHFBA)\n\nClinical features:\n- Profound global developmental delay\n- Hypotonia, muscle weakness, poor spontaneous movements\n- Rotary nystagmus\n- Respiratory distress, recurrent chest infections, poor feeding\n- Areflexia\n- Coarse facial features: thick eyebrows, hypertelorism, broad nasal bridge, short nose with upturned nasal tip, low-hanging columella, thick lips, low-set ears, high-arched palate, excessive facial hair, flat occiput\n- Mild cardiac defects (patient 1): small patent ductus arteriosus (PDA) and patent foramen ovale (PFO)\n- Hepatomegaly\n- Brain abnormalities: enlarged ventricles, reduced white matter volume, delayed myelination, hypoplastic corpus callosum, cavum septum pellucidum, cerebellar vermis hypoplasia\n- Variable features: atrial septal defect, hypertrophic cardiomyopathy, hepatosplenomegaly, scoliosis, abnormal thoracic cage\n- Ocular abnormalities: optic atrophy, esotropia, strabismus, poor vision, rotary nystagmus, blue sclerae\n- Dysmorphic features: high forehead, bitemporal narrowing, telecanthus, low-set ears, prominent nasal bridge, long philtrum, high-arched palate, tented mouth, small chin, increased facial hair, overall coarse features\n- Impaired intellectual development, absent language\n- Other features: mild short stature, muscle weakness, ataxia, hyporeflexia, scoliosis, left cardiac ventricular noncompaction\n- Brain abnormalities: localized pachygyria, asymmetric ventricles, thin corpus callosum, mega cisterna magna, periventricular white matter abnormalities, hypoplasia of the cerebellar vermis, atrophy of the cerebellar hemispheres", "DEVELOPMENTAL DELAY WITH VARIABLE INTELLECTUAL IMPAIRMENT AND BEHAVIORAL ABNORMALITIES": "Text 1: Moderate intellectual disability, ASD, craniosynostosis, TCF20 mutation.\nText 3: Global developmental delay, speech delay, intellectual disability, autism features, somatic overgrowth, movement abnormalities, dysmorphic features, sleep disturbances, seizures.\nText 5: Developmental delay, impaired intellectual development, neurologic abnormalities, dysmorphic features, motor and language delay, hypotonia, ASD, movement disorder, sleep disturbances, seizures, structural brain abnormalities, growth delay, macrocephaly, digital anomalies, somatic overgrowth, inverted nipples.\nText 4: Global developmental delay, intellectual disability, autistic features, attention disorders, hypotonia, motor delay, speech difficulties, ataxia, gait disturbance, spasticity, seizures, gastrointestinal problems, skeletal problems, ocular abnormalities, dysmorphic features, germline mosaicism.", "CONGENITAL HYPOTONIA, EPILEPSY, DEVELOPMENTAL DELAY, AND DIGITAL ANOMALIES": "Patients with this rare genetic disorder exhibit a range of neurodevelopmental and physical characteristics. These include dysmorphic facial features, cleft palate, hypotonia, hypertonia, polymicrogyria, cerebellar vermis hypoplasia, severe developmental delay, absent language, motor delay, visual and hearing impairments, seizures, EEG abnormalities, and skeletal anomalies. Other features may include feeding problems, sleep apnea, cryptorchidism, and abnormal brain imaging.", "MENTAL RETARDATION, AUTOSOMAL DOMINANT 21": "Text 1: Intellectual developmental disorder with CTCF gene mutation. Patient 1: mild intellectual disability, short stature, microcephaly, cleft palate, congenital heart defects. Patient 2: borderline intelligence, developmental delay, learning difficulties, behavioral problems, microcephaly. Patient 3: microcephaly, severe intellectual disability with autistic features, severe feeding difficulties.\n\nText 2: MRD21 with widely variable phenotype. Developmental delay, variable cognitive difficulties. Feeding anomalies, failure to thrive, behavioral anomalies common. Other findings: short stature, microcephaly, vision anomalies, recurrent infections, palatal anomalies, heart defects, hearing loss. Dysmorphic facial features: prominent forehead, bulbous nasal tip, long palpebral fissures. Phenotype not clinically recognizable.", "CLARK-BARAITSER SYNDROME": "Clinical features of the rare genetic disorder include impaired intellectual development, macrocephaly, square forehead, prominent supraorbital ridges, broad nasal tip, prominent lower lip, large ears, obesity, macroorchidism, tall stature, large hands, a gap between central incisors, normal eye spacing, behavior problems, dysmorphic facial features (such as hypertelorism, epicanthal folds, short nose, depressed nasal bridge, low columella, long philtrum, wide mouth, high-arched palate, and large ear lobes), and mild abnormalities of the hands or feet (such as clinodactyly and sandal gap).", "PAK1": "Neurodevelopmental disorder with impaired intellectual development, poor speech, postnatal macrocephaly, and seizures. Boy 1: delayed motor skills, multifocal and focal seizures, moderate cognitive impairment, severe speech impairment, macrocephaly, frontal bossing, long face, small ears, deep-set eyes, hyperlordosis. Boy 2: poor feeding, hypotonia, failure to thrive, unstable gait, delayed speech, intractable myoclonic seizures, moderate intellectual disability, very poor speech, macrocephaly, broad forehead, long face, small and deep-set eyes, strabismus. Brain imaging: normal for Boy 1, focal hyperintensities, delayed myelination for Boy 2.", "CONGENITAL CONTRACTURES OF THE LIMBS AND FACE, HYPOTONIA, AND DEVELOPMENTAL DELAY": "Clinical features of this rare genetic disorder include severe limb contractures, abnormal facial features (such as downslanting palpebral fissures, broad nasal bridge, and micrognathia), hypotonia, developmental delay, and intellectual impairment. Other common characteristics are camptodactyly, ulnar deviation, foot deformities, short neck, scoliosis, hip contractures, and respiratory distress. Brain MRI may show cerebellar and/or cerebral atrophy. Additional variable features include gastroesophageal reflux, hernias, and dysmorphic facies. The severity and specific manifestations of the disorder can vary among patients.", "WIEDEMANN-STEINER SYNDROME": "Clinical features of the rare genetic disorder include pre- and postnatal growth deficiency, psychomotor delay, round and flat face, short nose, hypertelorism, long philtrum, short palpebral fissures, low-set ears, high-arched palate, alternating convergent squint, dilatation of renal calyces, short and thick limbs, hairy elbows, short stature, rhizomelic shortening of limbs, heavy jaw, downslanting palpebral fissures, mild hypertelorism, thick alae, facial asymmetry, developmental delay, delayed speech, hypertrichosis of distal-lateral arms and proximal-lateral forearms, hypotonia, left-sided hypoplasia, left ptosis, epicanthal folds, dolichocephaly, telecanthus, synophrys, narrow and downslanting palpebral fissures, low nasal bridge, thin upper lip, sacral dimple, fifth finger clinodactyly, mild mental retardation, dolichocephaly, prominent forehead, low-set ears, triangular nostrils, short philtrum, high-arched palate, pectus excavatum, delayed bone age, mental retardation, hyperactivity, long eyelashes, thick or arched eyebrows, vertically narrow palpebral fissures, excessive hair on back, below 10th centile for height, sacral dimple, hypertelorism, broad nose, synophrys, short fingers and/or toes, hypotonia, failure to thrive, seizures, pericentric inversion of chromosome 9, interstitial duplication of chromosome 12q14.1, thick eyebrows, long eyelashes, generalized hirsutism, hypertrichosis of elbows and back, postnatal growth retardation, intellectual disability, broad nasal bridge, clinodactyly, fleshy hands, hypotonia, normal bone age, and phenotypic overlap with Kabuki syndrome.", "NAA15": "Patients with heterozygous variants in the NAA15 gene exhibit a range of neurodevelopmental disorders. Common features include developmental delay/intellectual disability (DD/ID), delayed speech and language, and autism spectrum disorder (ASD). Other characteristics may include motor delay, behavior problems, poor growth, and nonspecific dysmorphic features. Seizures and abnormal brain imaging are not typically observed. Additionally, some patients may have a family history of mild intellectual disability. The phenotype is variable, but all patients show some degree of neurodevelopmental disability, including impaired motor abilities, intellectual disability, language impairment, and behavioral abnormalities. Dysmorphic facial features, poor overall growth, short stature, fine motor problems, hypotonia, seizures, feeding difficulties, and cardiac anomalies may also be present. The phenotype of patients with MRD50, caused by mutations in the NAA15 gene, is highly variable and includes global developmental delay, speech delay, autism spectrum disorder, ADHD, and seizures. The severity of symptoms can range from mild to severe, with some individuals showing improvement and normal cognition over time.", "TRAIP": "Clinical features of the described rare genetic disorder include intrauterine growth retardation (IUGR), microcephaly, beaked nose, failure to thrive, early death, ambiguous external genitalia, renal and cardiac abnormalities, respiratory distress, and developmental delay. Other common characteristics include micrognathia, low-set ears, hypertrichosis, clubfeet, and dysmorphic facial features. Neuroimaging findings include reduced cerebral cortical size, simplified gyri, and enlarged ventricular system. Recurrent lower respiratory tract infections and urinary tract infections are also observed.", "POGZ": "Rare genetic disorder: POGZ gene mutations. Clinical features include intellectual disability, global developmental delay, behavioral/psychiatric problems, seizures, abnormal ear, hearing impairment, hypotonia, visual abnormalities, speech/language delay, autistic features, dysmorphic features, obesity, feeding difficulties, short stature, gastrointestinal manifestations, visual and hearing abnormalities, seizures, congenital anomalies, impaired intellectual development, speech delay, hypotonia, seizures, abnormal head imaging, facial features, ophthalmologic problems, hearing loss, gastrointestinal involvement, and sleep disorders.", "TREACHER COLLINS SYNDROME 1": "Clinical features of the rare genetic disorder, possibly an autosomal recessive form of Treacher Collins syndrome, include downward-slanting palpebral fissures, coloboma of the lower lids, malar hypoplasia, abnormal pinnae, intraorbital hollowness, prominent ears, delayed-onset infantile cataracts, hypoplasia of the zygomatic complex and mandible, conductive deafness, microtia, atresia of the external ear canal, and dental anomalies. Additional features may include encephalocele, malformation of the eyes, and extracraniofacial anomalies involving the thyroid, thymus, heart, spleen, adrenal gland, and external genitalia. Genotype/phenotype correlations are absent, and modifying factors influence phenotypic expression.", "LINEAR SKIN DEFECTS WITH MULTIPLE CONGENITAL ANOMALIES 1": "Clinical features of the rare genetic disorder include irregular areas of erythematous skin hypoplasia on the head and neck, microphthalmia, corneal opacities, orbital cysts, and diaphragmatic hernia. Other characteristics may include absence of the septum pellucidum, depigmented patches of skin, unerupted wisdom teeth, cardiomyopathy, genital anomalies, short stature, and agenesis of the corpus callosum. The disorder is distinct from focal dermal hypoplasia and incontinentia pigmenti. It is associated with X Y translocations and terminal deletions of the X chromosome at Xp22.3 or Xp22.2. The disorder is predominantly seen in females, but there have been cases in XX males. X inactivation may play a role in determining the phenotype.", "PYCR2": "Text 1: Nakayama et al (2015) reported 4 children with progressive postnatal microcephaly, hypomyelination, delayed psychomotor development, poor overall growth, truncal hypotonia, appendicular hypertonia, hyperreflexia, severe muscle wasting, nonverbal, abnormal facial features, and brain imaging abnormalities.\n\nText 2: Zaki et al (2016) reported 14 patients with HLD10, characterized by failure to thrive, microcephaly, profound psychomotor disability, dysmorphic facial features, neurologic features (hypotonia, spasticity, hearing loss, seizures), skeletal abnormalities, brain imaging abnormalities, and progressive nature leading to early death.\n\nBoth studies highlight intellectual disability, microcephaly, epilepsy, and brain abnormalities as key features of the rare genetic disorders.", "BURN-MCKEOWN SYNDROME": "Clinical features of the rare genetic disorder described in the texts include bilateral choanal atresia, cardiac defects, deafness, defects of the external ear, eyes and eyelids, and a characteristic dysmorphic appearance. Other common features include prominent ears, hypertelorism with short palpebral fissures, abnormalities of the outer third of the lower eyelid, malar and mandibular hypoplasia, orofacial clefting, and external ear malformation with preauricular tags. Intelligence is typically normal. Inheritance patterns may be autosomal recessive or X-linked.", "LEUKODYSTROPHY, HYPOMYELINATING, 10": "Text 1: Nakayama et al (2015) reported 4 children with progressive postnatal microcephaly, hypomyelination, delayed psychomotor development, poor overall growth, truncal hypotonia, appendicular hypertonia, hyperreflexia, severe muscle wasting, nonverbal, abnormal facial features, and brain imaging abnormalities.\n\nText 2: Zaki et al (2016) reported 14 patients with HLD10, characterized by failure to thrive, microcephaly, profound psychomotor disability, dysmorphic facial features, neurologic features (hypotonia, spasticity, hearing loss, seizures), skeletal abnormalities, brain imaging abnormalities, and progressive nature leading to early death.\n\nBoth studies highlight intellectual disability, microcephaly, epilepsy, and brain abnormalities as key features of the rare genetic disorders.", "MACROCEPHALY/AUTISM SYNDROME": "Clinical features of the rare genetic disorder include macrocephaly, typical facies with frontal bossing and midface abnormalities, long philtrum, normal birth weight and length with subsequent obesity. Some individuals also exhibit autistic characteristics, attention deficit disorder, delays in language and social development, and progressive postnatal macrocephaly. Other features may include pigmented macules, dysmorphism, and immunodeficiency with recurrent infections and abnormal immunologic findings. PTEN mutations are associated with macrocephaly and autism, while loss-of-function mutations in PTEN and PIK3CD gene cause increased PI3K signaling in lymphocytes.", "MENTAL RETARDATION, AUTOSOMAL DOMINANT 57": "Patients with MRD57, associated with TLK2 gene variants, exhibit delayed development, intellectual disability, behavioral abnormalities (including autism spectrum disorder and anxiety), hypotonia, epilepsy, joint hypermobility, craniosynostosis, dysmorphic features (such as blepharophimosis and upslanting palpebral fissures), short stature, microcephaly, feeding difficulties, and gastrointestinal issues.", "PREMATURE AGING SYNDROME, PENTTINEN TYPE": "Clinical features of the rare genetic disorder include prematurely aged appearance, delayed bone maturation, dental abnormalities, acroosteolysis with brachydactyly, and distinctive cutaneous findings. Other characteristics include hyperopia, sensorineural hearing loss, elevated thyroid stimulating hormone levels, and normal linear growth and intellectual functions. Patients may exhibit progeroid facial features, large thumbs and halluces, sparse hair, ocular pterygia, keloid-like skin lesions, and increased linear growth. Complications such as kyphoscoliosis, skin retraction, joint contractures, and respiratory insufficiency may arise. Additional features include multiple fractures, scoliosis, osteoporosis, open fontanels, facial abnormalities, severe contractures, thin skin with venous patterning, and hyperkeratotic palms and soles. Intelligence may vary among affected individuals.", "ACROFACIAL DYSOSTOSIS, CINCINNATI TYPE": "Acrofacial dysostosis, Cincinnati type, is characterized by craniofacial anomalies such as downslanting palpebral fissures, lower eyelid clefts, underdeveloped midface, and micrognathia. Other features include anotia, conductive hearing loss, short stature, and decreased head circumference. CT scans reveal hypoplasia of zygomatic arches, maxilla, and mandible. Limb anomalies may include short, bowed femurs, dysplastic acetabula, and delayed ossification. In some cases, choanal atresia and microcephaly may be present.", "KAT6A": "Text 1: Children with microcephaly, poor growth, delayed development, intellectual disability, absent speech, hypotonia, dystonia, dysmorphic facial features, cleft palate, optic nerve atrophy, heart defects, lung disease, reflux, feeding difficulties, and intestinal malrotation.\n\nText 2: Patients with mutations in the KAT6A gene, impaired intellectual development, speech delay, microcephaly, broad nasal tip, thin upper lip, facial dysmorphisms, congenital heart disease, feeding difficulties, reflux, constipation, visual defects, strabismus, and sleep problems.\n\nText 3: Boy with developmental delay, failure to thrive, microcephaly, hypotonia, hypertonia, undescended testis, heart defects, dysmorphic facial features, severe myopia.\n\nNote: The summaries have been condensed to fit within the token limit.", "ARBOLEDA-THAM SYNDROME": "Text 1: Children with microcephaly, poor growth, delayed development, intellectual disability, absent speech, hypotonia, dystonia, dysmorphic facial features, cleft palate, optic nerve atrophy, heart defects, lung disease, reflux, feeding difficulties, and intestinal malrotation.\n\nText 2: Patients with mutations in the KAT6A gene, impaired intellectual development, speech delay, microcephaly, broad nasal tip, thin upper lip, facial dysmorphisms, congenital heart disease, feeding difficulties, reflux, constipation, visual defects, strabismus, and sleep problems.\n\nText 3: Boy with developmental delay, failure to thrive, microcephaly, hypotonia, hypertonia, undescended testis, heart defects, dysmorphic facial features, severe myopia.\n\nNote: The summaries have been condensed to fit within the token limit.", "ROBINOW SYNDROME, AUTOSOMAL DOMINANT 1": "Clinical features of the rare genetic disorder, Robinow syndrome, include short stature, bulging forehead, depressed nasal bridge, short limbs, increased interorbital distance, malaligned teeth, and normal vaginal delivery by affected females. Other characteristics may include small or absent penis, hemivertebrae, normal pubertal virilization with persistence of micropenis, elevated follicle-stimulating hormone levels, normal to borderline adult height, and characteristic facies. Umbilical changes, renal scarring, dislocatable hip, and craniofacial dysmorphology may also be present. The syndrome can be inherited in an autosomal dominant or recessive pattern, with the recessive form being more severe. Differential diagnosis can be aided by noting differences in intraoral characteristics.", "AYME-GRIPP SYNDROME": "Rare genetic disorder: Congenital cataracts, sensorineural deafness, distinctive facial appearance, skeletal changes, postnatal short stature, mental retardation. Similarities observed in multiple patients. Possible association with chromosome 11q deletion.", "MANDIBULOFACIAL DYSOSTOSIS WITH ALOPECIA": "Clinical features of the rare genetic disorder, mandibulofacial dysostosis with alopecia (MFDA), include scalp alopecia, malformed ears, facial asymmetry, horizontal palpebral fissures, thin lashes, displaced lacrimal punctae, eyelid coloboma, preauricular pits and tags, abnormal lower eyelids, sparse eyebrows and eyelashes, zygomatic hypoplasia, broad nasal bridge and tip, micrognathia, cleft palate, alopecia, delayed dentition, hearing loss, and dental anomalies. Maxillary dysmorphism, dysplastic zygomatic arch, and hypoplastic mandible are also observed.", "CUTIS LAXA, AUTOSOMAL DOMINANT 3": "Rare genetic disorder: extreme joint hypermobility, lax skin, cataracts, severe growth retardation, insufficient production of procollagens, oligohydramnios, poor fetal growth, small size at birth, thin and translucent skin, increased visibility of veins, reduced subcutaneous fat tissue, hernia, loose joints with dislocation, clubfoot, large head with frontal bossing, open fontanels and cranial sutures, facial resemblance to geroderma osteodysplasticum, bilateral cataracts, volar flexion of wrists with adducted thumbs, asymmetric skull, wormian bones, scoliosis, agenesis of right kidney, progressive spinal stenosis, thin and insufficient aortic valve, progeroid de Barsy-like cutis laxa phenotype, triangular face, prominent forehead, cataracts or corneal clouding, low-set ears, prenatal and postnatal growth retardation, lax and thin skin with visible veins, joint hyperlaxity, adducted thumbs, cranial vessel tortuosity, delayed psychomotor development, autism spectrum disorder, brisk peripheral reflexes, foramen magnum stenosis.", "IMPAIRED INTELLECTUAL DEVELOPMENT AND DISTINCTIVE FACIAL FEATURES WITH OR WITHOUT CARDIAC DEFECTS": "Clinical features of the rare genetic disorder include congenital heart defects (DTGA, VSD, coarctation of the aorta), microcephaly, delayed motor development, impaired intellectual development, facial dysmorphism, hypotonia, dysarthria, and dysmorphic facial features. Other characteristics include delayed psychomotor development, poor speech, open-mouth appearance, and various dysmorphic features such as low-set ears, flat nasal bridge, and macrostomia. Some patients also exhibit ataxia, seizures, and recurrent infections. Reduced penetrance of severe cardiac abnormalities is observed in some cases. Phenotypic similarities to the 1p36 deletion syndrome are noted.", "MENTAL RETARDATION, AUTOSOMAL DOMINANT 58": "Rare genetic disorder characterized by delayed development, intellectual disability, language delay, and speech impairment. Some patients exhibit motor delay or incoordination, but all can walk. Minor dysmorphic features include facial asymmetry, high palate, dental crowding, hypertelorism, plagiocephaly, small head circumference, large ears, broad nasal bridge, thick lips, and wide mouth. Additional features may include hypotonia, hypermobility, and occasional seizures. Brain imaging, when performed, shows normal results.", "AL-RAQAD SYNDROME": "Text 1: Delayed psychomotor development, microcephaly, congenital hypotonia, severe growth delay, dysmorphic facial features, joint laxity, brachydactyly, sandal gap, skin hypopigmentation, atrial septal defects. Normal brain imaging.\n\nText 2: Delayed psychomotor development, intellectual disability, absent speech, possible prominent upper jaw, microcephaly, severely delayed motor development, hypotonia, normal brain imaging, no abnormalities of skin, hair, joints, vision, or hearing.\n\nText 3: Mutation in the DCPS gene, below 3rd centile for height, weight, and head circumference, respiratory distress, atrial septal defect, feeding intolerance, recurrent respiratory infections, sleep apnea, growth delay, psychomotor delay, reduced subcutaneous tissue, hypotrophic muscle mass, dysmorphic facial features, short neck, brachydactyly, fifth finger clinodactyly, blond hair, pigmentary skin anomalies along Blaschko lines.", "TATTON-BROWN-RAHMAN SYNDROME": "Rare genetic disorder: Tatton-Brown-Rahman syndrome (TBRS)\nPhenotype characteristics:\n- Tall stature (+3.0 SD)\n- Large head circumference (+2.5 SD)\n- Round face, heavy horizontal eyebrows, narrow palpebral fissures\n- Intellectual disability (moderate to mild)\n- Less common features: atrial septal defects, seizures, umbilical hernia, scoliosis\n- No hematologic malignancy in patients\n- Atypical features in some patients: severe intellectual disability, short stature, coarse facies\n- TBRS associated with DNMT3A gene mutation\n- Increased risk of hematopoietic malignancies (AML, lymphomas, leukemia)\n- Annual monitoring of blood counts recommended", "WITTEVEEN-KOLK SYNDROME": "Rare genetic disorder: Intellectual disability, delayed development, speech delay, autistic behavior, seizures, dysmorphic facial features (broad forehead, long face, downslanting palpebral fissures, flat nasal bridge, large fleshy ears, long smooth philtrum, small mouth, pointed chin), short stature, microcephaly, joint hypermotility, small hands and feet, brain abnormalities (dilated ventricles, thin corpus callosum, dysgyria/polymicrogyria). Chromosome 15q24 deletion syndrome: Growth retardation, psychomotor retardation, dysmorphic facial features, microcephaly, microphthalmia, hypertelorism, open mouth, high-arched palate, large ears, digital anomalies, cardiovascular abnormalities. Chromosome 15q24 duplication syndrome: Global developmental delay, dysmorphic facial features, low-set ears, broad nasal bridge, hypertelorism, epicanthal folds, smooth philtrum, hypoplastic nails, hypotonia.", "LARSEN SYNDROME": "Rare genetic disorder: Larsen syndrome\nPhenotype characteristics: \n- Multiple congenital dislocations\n- Characteristic facies: prominent forehead, depressed nasal bridge, wide-spaced eyes\n- Clubfoot\n- Bilateral dislocation of elbows, hips, and knees\n- Short metacarpals with cylindrical fingers\n- Cleft palate, hydrocephalus, and spinal abnormalities in some cases\n- Juxtacalcaneal accessory bone\n- Oral and craniofacial findings\n- Mixed hearing loss\n- Laryngomalacia with apnea and cervical spine abnormalities\n- Cervical kyphosis, potentially life-threatening\n- Pseudoclubbing of fingers and toes\n- Genua recurvata (fixed extended position of knees)\n- Dysmorphic facial features: flat nose, micrognathia\n- Misdiagnosis and underestimation of cervical kyphosis\n- Possible mosaicism in mild cases", "MICROCEPHALY 6, PRIMARY, AUTOSOMAL RECESSIVE": "Rare genetic disorder: Autosomal recessive primary microcephaly\n- Severe mental retardation\n- Microcephaly (-4 to -17 SD)\n- Small ears\n- Hypertelorism\n- Strabismus\n- Notched nasal tip\n- Seizures\n- Joint stiffness\n- Wheelchair requirement\n- Inability to speak or write", "MARSHALL SYNDROME": "Clinical features of Marshall syndrome include nasal defect and facies characteristic of anhidrotic ectodermal dysplasia, congenital and juvenile cataracts, myopia and fluid vitreous, spontaneous sudden maturation and absorption of congenital cataract, luxation of cataract, and congenital hearing loss. Other features may include defects in sweating, dental structures, and craniofacial abnormalities. There is overlap with Stickler syndrome, Wagner syndrome, and Weissenbacher-Zweymuller syndrome, but Marshall syndrome is distinct due to the rarity of cleft palate and deafness. Radiologic findings may include calvarial thickening, intracranial calcifications, and narrowed joint spaces.", "HYPERPHOSPHATASIA WITH MENTAL RETARDATION SYNDROME 1, Hyperphosphatasia with mental retardation syndrome": "Rare genetic disorder characterized by severe mental retardation, seizures, and elevated alkaline phosphatase. Other features include neurologic abnormalities, delayed motor and speech development, hypoplastic terminal phalanges, hypoplastic nails, hypotonia, delayed myelinization in the brain, distinct facial features (hypertelorism, downturned corners of the mouth), and various congenital anomalies (anteriorly displaced anus, clefting of the palate, anovestibular fistula, ventricular septal defect). Patients may have intracellular inclusions in some tissues. The disorder is associated with hyperphosphatasia and is distinct from Coffin-Siris syndrome.", "CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IIB": "Rare genetic disorder with overlapping features of geroderma osteodysplastica (GO) and wrinkly skin syndrome (WSS). Dysmorphic facial features, including broad forehead, hypotelorism, bulbous nose, flat malar region, and large protruding ears. Wrinkling of skin, hyperextensibility of joints, and aged appearance. Intrauterine growth retardation, failure to thrive, developmental delay, and osteoporosis. Prognathism in older children. Corpus callosum agenesis and high third ventricle observed in some cases. Cutis laxa, microcephaly, osteopenia, and mental retardation in other cases. Lax, wrinkled skin with reduced elasticity, lax joints, and craniofacial dysmorphism. Intrauterine growth retardation, postnatal growth deficiency, and developmental delay. Some cases with agenesis of the corpus callosum and enlarged ventricles.", "HYPERPHOSPHATASIA WITH MENTAL RETARDATION SYNDROME 3, Hyperphosphatasia with mental retardation syndrome": "Rare genetic disorder characterized by severe mental retardation, seizures, neurologic abnormalities, and elevated alkaline phosphatase. Other features include delayed motor and speech development, hypoplastic terminal phalanges, hypoplastic nails, hypotonia, delayed myelinization in the brain, distinct facial features (hypertelorism, downturned corners of the mouth), and various congenital anomalies (anteriorly displaced anus, clefting of the palate, anovestibular fistula). Inclusions found in some tissues. Designated as Mabry syndrome.", "HYPERPHOSPHATASIA WITH MENTAL RETARDATION SYNDROME 4, Hyperphosphatasia with mental retardation syndrome": "Clinical features of HPMRS4 include severely delayed psychomotor development, hypotonia, inability to speak or walk independently, seizures, dysmorphic facial features (hypertelorism, upslanting palpebral fissures, broad nasal bridge, short nose, long philtrum, tented upper lip, full cheeks, large fleshy earlobes), postnatal microcephaly, cleft palate, thin corpus callosum, dilated lateral ventricles, increased serum alkaline phosphatase, and absence of brachytelephalangy. Other features may include megalocornea, abnormal dentition, hearing loss, and congenital heart defects. The disorder is characterized by elevated alkaline phosphatase levels and may be associated with intracellular inclusions.", "MICROCEPHALY 1, PRIMARY, AUTOSOMAL RECESSIVE": "Clinical features of this rare genetic disorder include true microcephaly with no neurologic defect other than mental deficiency, no skeletal or other malformation, and reduced brain weight in adolescence leading to death in majority before age 30. It is associated with short stature, mental retardation, hypergonadotropic hypogonadism, and minor anomalies. Recurrent microcephaly is common, with spastic quadriplegia, seizures, and profound mental handicap. Head circumference is not a reliable indicator of brain size. Cognitive functions are reduced, but motor skills are preserved. Neuronal precursor cells in the neuroepithelium are affected, resulting in reduced production of functional neurons. Chromosome abnormalities and mutations in the MCPH1 gene have been identified.", "SAETHRE-CHOTZEN SYNDROME": "Clinical features of the rare genetic disorder include mild acrocephaly, asymmetry of the skull, partial soft tissue syndactyly of fingers and toes, thin and long nose, cleft palate, hydrophthalmos, cardiac malformation, contractures of elbows and knees, asymmetry of the face, unusually shaped ear, simian crease, craniosynostosis, symmetrical syndactyly of toes, short columella, small pinnae, fusion of cervical vertebrae, duplication of first metatarsal, bifid distal phalanges, and anal malposition/stenosis. Different mutations in TWIST1 and FGFR2 genes are associated with distinct phenotypic variations, distinguishing Saethre-Chotzen syndrome from Muenke syndrome.", "OTOPALATODIGITAL SYNDROME, TYPE II, OTOPALATODIGITAL SYNDROME, TYPE I": "Clinical features of the rare genetic disorder include conduction deafness, cleft palate, characteristic facies, generalized bone dysplasia, broad nasal root, wide-spacing of the toes, conductive hearing loss, broad thumbs and great toes, short fingernails, fifth finger clinodactyly, dislocation of the head of the radius, pectus excavatum, mild dwarfism, secondary ossification center at the base of the second metacarpal and metatarsal, hypertelorism, median frontal prominence, scoliosis, absence or mild expression in females, mental retardation not a feature, omphalocele, hypospadias, hydronephrosis, chordee, hydrocephalus, absent fibulae, increased bone density, prominent forehead, antimongoloid slant of palpebral fissures, flattened nasal bridge, retrogenia, skeletal abnormalities, conductive hearing impairment, limited joint mobility, supernumerary carpal bones, cognitive impairment, defective intramembranous ossification, defective periosteal ossification, islands of cortical bone aplasia, hyperplasia of periosteum, poorly formed trabecular bone, involvement of biglycan gene, downslanting palpebral fissures, small mouth, deformed pelvic bones, bowed femurs and tibias, absent fibulas, 4-toed configuration of feet, tracheomalacia requiring tracheostomy.", "ALAGILLE SYNDROME 1, Alagille syndrome": "Clinical features of this rare genetic disorder include neonatal jaundice, posterior embryotoxon and retinal pigmentary changes in the eye, pulmonic valvular stenosis and peripheral arterial stenosis in the heart, abnormal vertebrae and decreased interpediculate distance in the bones, absent deep tendon reflexes and poor school performance in the nervous system, broad forehead, pointed mandible, and bulbous tip of the nose in the facies, and varying degrees of foreshortening in the fingers. Histology of the liver shows few intrahepatic bile ducts. Other features may include renal dysplasia, ocular abnormalities, and cardiovascular involvement such as moyamoya syndrome and vascular anomalies.", "CHARGE SYNDROME": "Clinical features of CHARGE syndrome include choanal atresia, coloboma of the eye, heart anomalies, mental and somatic development retardation, microphallus, ear abnormalities and/or deafness. Other associated features include facial palsy, cleft palate, dysphagia, feeding difficulties, and dysmorphic facial appearance. Additional features may include genital hypoplasia, growth retardation, nail hypoplasia, and CNS malformations. The syndrome is characterized by a high mortality rate in infants with certain combinations of features. Diagnosis is based on the presence of multiple major features. Genetic factors such as de novo dominant mutation or subtle submicroscopic chromosome rearrangement may play a role. Hypogonadotropic hypogonadism is responsible for genital hypoplasia and lack of secondary sexual development. Semicircular canal agenesis and arhinencephaly are highly predictive diagnostic criteria. Behavior and medical problems may be associated, with heart defects and cardiac surgery potentially influencing behavioral problems. CHD7 mutations are responsible for CHARGE syndrome, and somatic mosaicism may occur in parents. Cranial nerve anomalies, including olfactory defects, are common. Screening for additional clinical features is recommended in patients with anosmia and/or hypogonadotropic hypogonadism.", "BRANCHIOOCULOFACIAL SYNDROME": "Clinical features of the rare genetic disorder include low birth weight, retarded postnatal growth, branchial cleft sinuses, strabismus, nasolacrimal duct obstruction, broad nasal bridge, protruding upper lip, carp mouth, premature graying of hair, normal intelligence, coloboma, microphthalmia, auricular pits, lip pits, highly arched palate, dental anomalies, subcutaneous scalp cysts, agenesis of the cerebellar vermis, cleft lip and palate, ocular abnormalities, hearing loss, polydactyly, renal anomalies, and mutations in the TFAP2A gene.", "ECTODERMAL DYSPLASIA 1, HYPOHIDROTIC, X-LINKED": "Clinical features of this rare genetic disorder include characteristic facies in affected males, such as frontal bossing, maxillary hypoplasia, 'saddle' nose, prominent lips, and linear wrinkles around the eyes. Teeth are often missing or misshapen, hair is fine, dry, brittle, and sparse, and skin is thin, glossy, smooth, and dry with hypohidrosis. Females may have sparse, thin scalp hair and mosaic patchy distribution of body hair, as well as abnormal teeth and mild hypohidrosis. The disorder is highly penetrant and X-linked, with intermediate expression in heterozygous females. Other clinical findings include immunodeficiency, respiratory infections, and dental abnormalities.", "COFFIN-SIRIS SYNDROME 1, Coffin-Siris syndrome": "Rare genetic disorder: Coffin-Siris syndrome (CSS)\nPhenotype characteristics:\n- Mental retardation\n- Absent or hypoplastic fifth fingernails/toenails and phalanx\n- Hypertrichosis (excessive hair growth)\n- Dysmorphic facial features (low anterior hairline, thick arched eyebrows, broad nose, thick lips)\n- Rough skin with hyperkeratotic plaques\n- Broad feet and fingertips\n- Short stature\n- Behavioral abnormalities (obsessive-compulsive disorder, withdrawal, stubbornness, autistic features)\n- Limited language with hoarse or high-pitched voice\n- Mild nail hypoplasia\n- Coarse facies\n- Myopia, strabismus\n- Mild short stature\n- Muscular hypotonia\n- Abnormal head shape, low-set and abnormally shaped ears\n- Downslanting palpebral fissures\n- Bulbous nasal tip, thin upper lip\n- Brachydactyly or single palmar creases\n- Frequent infections\n- Intellectual disability, severe speech delay\n- Agenesis or hypoplasia of the corpus callosum\n- Deletions involving ARID1B gene\n- Variability in the complete CSS phenotype", "CLEIDOCRANIAL DYSPLASIA": "Clinical features of the rare genetic disorder include \"Arnold head\" phenotype, delayed eruption of teeth, cleidocranial dysplasia, scoliosis, syringomyelia, growth retardation, decreased height and radius length, extra epiphyses in metacarpals, hypoplastic clavicles, fontanels and wormian bones, hand abnormalities, and underossification of the hyoid bone.", "HURLER SYNDROME": "Clinical features of Hurler syndrome include coarse facies, corneal clouding, mental retardation, hernias, dysostosis multiplex, and hepatosplenomegaly. Other characteristics include short neck, odontoid hypoplasia, cardiovascular abnormalities, respiratory obstruction, musculoskeletal abnormalities, developmental delay, and dermal melanocytosis.", "RUBINSTEIN-TAYBI SYNDROME 1, Rubinstein-Taybi syndrome": "Clinical features of Rubinstein-Taybi syndrome (RSTS) include mental retardation, broad thumbs and toes, facial abnormalities, juvenile glaucoma, talon cusps, pheochromocytoma, broad halluces, persistent fetal pads, shawl scrotum, frequent fractures, constipation, collapsible laryngeal walls, short upper lip, pouting lower lip, high slit-like palate, phenotypic overlap with Saethre-Chotzen syndrome, agenesis of the corpus callosum, iris coloboma, megacolon, pulmonary hypertension, mitral valve regurgitation, patent ductus arteriosus, cardiac abnormalities, increased risk of tumor formation, slipped capital femoral epiphysis, patellar dislocation, premature thelarche, defective antibody response, orodental features, varicella meningoencephalitis, visual difficulties, keloids, eating problems, spinal curvature, joint laxity, behavioral problems, and growth abnormalities. Incomplete RSTS may present with broad thumbs, antimongoloid slant of the palpebral fissures, beaked nose, and characteristic facial appearance.", "PIERPONT SYNDROME": "Clinical features of Pierpont syndrome include global developmental delay, microcephaly, midface hypoplasia, enlarged fleshy ears, depressed nasal bridge, anteverted nostrils, high forehead, bilateral congenital fat pads, deep palmar and plantar grooves, and pillowing of soft tissues. Other characteristics may include axial hypotonia, feeding problems, speech delay, distinct facial phenotype, short neck, small penis and scrotum, excessive skin over hands and feet, widely spaced teeth, learning disability, narrow palpebral fissures, microcornea, scoliosis, short fingers and toes, hearing loss, microphthalmia, pendular nystagmus, cryptorchidism, dermal sinus, peripheral joint laxity, growth restriction, intellectual impairment, Chiari malformation, gyration disorder, atypical fat distribution, and syndactyly.", "NICOLAIDES-BARAITSER SYNDROME": "Clinical features of Nicolaides-Baraitser syndrome include mental retardation, sparse hair, prominent lower lip, brachydactyly, swelling of interphalangeal joints, seizures, language loss, short stature, obesity, alopecia, skin wrinkling, dysmorphic facial features, cryptorchidism, cone-shaped epiphyses, hypotrichosis, epilepsy, and severe mental delay. Other characteristics include triangular face, narrow palpebral fissures, periorbital sagging, narrow nasal bridge, broad nasal tip, wide mouth, thin upper vermilion border, thick lower vermilion border, and prominent finger joints. The syndrome is associated with intellectual disability, microcephaly, low birth weight, and poor growth. It is distinguishable from Coffin-Siris syndrome and is caused by mutations in the SMARCA2 gene.", "KABUKI SYNDROME 1, Kabuki syndrome": "Clinical features of Kabuki syndrome include:\n1. Peculiar facial characteristics: eversion of lower lateral eyelid, arched eyebrows, depressed nasal tip, prominent ears.\n2. Skeletal anomalies: brachydactyly V, spinal deformity, cleft vertebrae.\n3. Dermatoglyphic abnormalities: increased digital ulnar loop, hypothenar loop patterns, absence of digital triradius c and/or d, fingertip pads.\n4. Mild to moderate mental retardation.\n5. Postnatal growth deficiency.\n6. Fetal finger pads.\n7. Congenital heart defects.\n8. Early breast development in some infant girls.\n9. Autosomal dominant inheritance with variable expressivity.\n10. Variable additional features: cleft palate, diaphragmatic hernia, hepatic anomalies, hearing loss, oral manifestations, behavioral phenotype, immune deficiency, and others.", "NIJMEGEN BREAKAGE SYNDROME": "Clinical features of this rare genetic disorder, known as Nijmegen Breakage Syndrome (NBS), include microcephaly, microgenia, 'bird-like' facies, immunodeficiency, and normal serum levels of alpha-fetoprotein. Patients also exhibit chromosomal instability, particularly involving chromosomes 7 and 14, and are hypersensitive to irradiation. NBS is distinct from Ataxia-Telangiectasia (AT), as patients with NBS do not have ataxia or telangiectasia. Other features include stunted growth, mental retardation, cafe-au-lait spots, and an increased risk of lymphoreticular malignancies. NBS is inherited in an autosomal recessive manner.", "MOWAT-WILSON SYNDROME": "Clinical features of Mowat-Wilson syndrome include distinctive facial phenotype, mental retardation, microcephaly, short stature, Hirschsprung disease, epilepsy, congenital heart defects, agenesis of the corpus callosum, and characteristic facial features such as hypertelorism, convergent strabismus, and broad nasal bridge. Other features may include deafness, pigmentation defects, iris coloboma, ptosis, cleft palate, hypospadias, and agenesis of the corpus callosum. The syndrome is caused by mutations or deletions in the ZFHX1B gene. Neuroimaging findings may include anomalies of the corpus callosum, hippocampal abnormalities, enlargement of cerebral ventricles, and white matter abnormalities. Patients may also exhibit behavioral problems and have abnormal eye malformations.", "SOTOS SYNDROME 1, Sotos syndrome": "Abnormality of the cardiovascular system Flushing Broad forehead Seizure Dolichocephaly Autistic behavior Downslanted palpebral fissures Global developmental delay Scoliosis Long face Ventriculomegaly Abnormality of the kidney Accelerated skeletal maturation Abnormal mandible morphology Sparse anterior scalp hair Soft, doughy skin Overgrowth", "WAARDENBURG SYNDROME, TYPE 3, WAARDENBURG SYNDROME, TYPE 1, Waardenburg syndrome": "Clinical features of the rare genetic disorder, Waardenburg syndrome, include limb anomalies, pigmentary defects, and sensorineural hearing loss. Other characteristics include facial changes, winged scapulae, upper limb abnormalities (such as hypoplasia, contractures, fusion of carpal bones, and syndactyly), microcephaly, mental retardation, spastic paraplegia, dystopia canthorum, blepharophimosis, flexion contractures of fingers, and white forelock. Prevalence of hearing loss varies according to genotype, with WS1 due to PAX3 mutations having a prevalence of 52.3% to 57.1%.", "TREACHER COLLINS SYNDROME 1, Treacher Collins syndrome": "Clinical features of the rare genetic disorder, possibly an autosomal recessive form of Treacher Collins syndrome, include downward-slanting palpebral fissures, coloboma of the lower lids, malar hypoplasia, abnormal pinnae, intraorbital hollowness, prominent ears, delayed-onset infantile cataracts, hypoplasia of the zygomatic complex and mandible, conductive deafness, microtia, atresia of the external ear canal, and dental anomalies. Additional features may include encephalocele, malformation of the eyes, and extracraniofacial anomalies involving the thyroid, thymus, heart, spleen, adrenal gland, and external genitalia. Genotype/phenotype correlations are absent, and modifying factors influence phenotypic expression.", "SMITH-MAGENIS SYNDROME": "Clinical features of the rare genetic disorder associated with interstitial deletion of chromosome 17p11.2 include mental retardation, hypotonia, speech delay, small ears, conductive hearing loss, esotropia, dental enamel dysplasia, and prominent premaxilla. Additional characteristics may include brachycephaly, midface hypoplasia, prognathism, hoarse voice, psychomotor and growth retardation, behavioral problems, facial malformations, cleft palate, cardiac anomalies, skeletal anomalies, genitourinary anomalies, broad flat midface with brachycephaly, broad nasal bridge, brachydactyly, decreased or absent deep tendon reflexes, pes planus or pes cavus, decreased sensitivity to pain, decreased leg muscle mass, self-destructive behavior, sleep disturbance, absence of REM sleep, otolaryngologic abnormalities, eye abnormalities, hearing impairment, scoliosis, brain abnormalities, cardiac abnormalities, renal abnormalities, low thyroxine levels, low immunoglobulin levels, forearm abnormalities, and a range of IQ scores falling in the moderate to mild range of mental retardation. Diagnosis can be made through cytogenetic analysis or by an experienced clinician based on the distinctive phenotype.", "BORJESON-FORSSMAN-LEHMANN SYNDROME": "Clinical features of this rare genetic disorder include severe mental defect, epilepsy, hypogonadism, hypometabolism, marked obesity, swelling of subcutaneous tissue of face, narrow palpebral fissure, large but not deformed ears, prominent superciliary ridges, deep-set eyes, ptosis, learning problems, moderate short stature, truncal obesity, gynecomastia, tapering fingers, shortened toes, heavy facial appearance, and skewed X inactivation. In females, manifestations may include hyperkyphosis, no menarche, sudden death, hypotonia, obesity, diabetic ketoacidosis, 'coarse' face, small hands, amenorrhea, hypothyroidism, epilepsy, learning difficulties, psychomotor retardation, shallow forehead, fleshy earlobes, broad feet, hammertoes, and hypoplastic fifth digits.", "LIG4 SYNDROME": "Clinical features of the rare genetic disorder, LIG4 syndrome, include immunodeficiency, developmental and growth delay, unusual facial features, microcephaly, pancytopenia, and various skin abnormalities. Patients also exhibit pronounced radiosensitivity and impaired DNA double-strand break rejoining. Additionally, a small decrease in rejoining frequency and elevated imprecision at signal junctions in V(D)J recombination is observed. Some patients may also present with acute T-cell leukemia and chromosomal breakage. Another variant of the disorder may manifest as severe combined immunodeficiency with sensitivity to ionizing radiation, recurrent infections, and decreased immunoglobulins.", "CRANIOFRONTONASAL SYNDROME": "CFNS is a rare genetic disorder characterized by hypertelorism, craniosynostosis, craniofacial asymmetry, frontal bossing, downslanting palpebral fissures, clefting of the nasal tip, longitudinally grooved fingernails, and other digital anomalies. It predominantly affects females and can also present with brachycephaly, high-arched palate, thick and low-set ears, short neck, cryptorchidism, and various skeletal abnormalities. CFNS is associated with X-linked dominant inheritance and can manifest with thick, wiry hair. Other features include syndactyly, pectus excavatum, diaphragmatic hernia, and intellectual disability. CFNS can be confirmed through molecular analysis and may be associated with mutations in the EFNB1 gene.", "COSTELLO SYNDROME": "Clinical features of Costello syndrome include short stature, redundant skin of the neck, palms, soles, and fingers, curly hair, papillomata around the mouth and nares, mental retardation, aged facial appearance, thin anterior hair of the head, epicanthal folds, large depressed nasal bridge, large earlobes, thickened and hyperkeratotic skin over the hands and feet, dark skin color, feeding problems, abnormal speech, acanthosis nigricans, abnormal glucose metabolism, failure to thrive, cardiomyopathy, furrowing of palmar creases, sialuria, oral motor apraxia, coarse face, wide hirsute forehead, wide anteverted nostrils, thick lips, multiple congenital anomalies/mental retardation, sociable and humorous behavior, skeletal abnormalities, low-set ears with large/thick lobes, hypertrophic cardiomyopathy, tachyarrhythmias, bladder carcinoma, rhabdomyosarcoma, transitional cell carcinoma of the bladder, neural crest neoplasia, and increased risk of malignancy.", "MUCOPOLYSACCHARIDOSIS, TYPE II, Mucopolysaccharidoses": "Clinical features of Hurler syndrome include coarse facies, corneal clouding, mental retardation, hernias, dysostosis multiplex, and hepatosplenomegaly. Other common characteristics include cardiovascular abnormalities, respiratory obstruction, musculoskeletal deformities, and neurological decline. In Hunter syndrome, clinical manifestations include severe airway obstruction, skeletal deformities, cardiomyopathy, and neurologic decline. Both disorders exhibit a wide range of clinical variability.", "DONNAI-BARROW SYNDROME": "Rare genetic disorder characterized by ocular and facial anomalies (telecanthus, hypertelorism), sensorineural deafness, myopia, proteinuria, diaphragmatic hernia, exomphalos, agenesis of the corpus callosum, and developmental delay. Autosomal recessive inheritance. Additional features include iris coloboma, retinal detachment, macular and iris hypoplasia, cataract, high myopia, and nonacidotic proximal tubulopathy. Imaging reveals brain anomalies and urine samples show proteinuria with retinol-binding and vitamin D-binding protein spillage.", "OCULODENTODIGITAL DYSPLASIA, OCULODENTODIGITAL DYSPLASIA, AUTOSOMAL RECESSIVE": "Clinical features of the rare genetic disorder include bilateral microphthalmia, abnormally small nose, hypotrichosis, dental anomalies, fifth finger camptodactyly, syndactyly of the fourth and fifth fingers, missing toe phalanges, microcornea, glaucoma, enamelogenesis imperfecta, widened phalanges and metacarpals, spastic paraplegia, cognitive impairment, subcortical white matter lesions, curly hair, trichorrhexis nodosa, keratoderma, dental abscess, taurodontism, optic nerve and retinal dysplasia, ciliary body cysts, telecanthus, epicanthal folds, malformed teeth, soft tissue syndactyly of toes, skeletal changes, cranial hyperostosis, mandibular overgrowth, spinal cord compression, calcification of basal ganglia, hypotonia, micrognathia, delayed tooth eruption, sparse hair, gross motor and speech delay, short stature, triangular face, brachycephalic head, psychomotor retardation, deficiency of growth hormone and insulin-like growth factor-1.", "UROFACIAL SYNDROME 1, Urofacial syndrome": "Clinical features of the rare genetic disorder, known as Urofacial Syndrome (UFS), include hydronephrosis, hydroureter, and a peculiar facial expression that is mainly observed when smiling or crying. Urethral valves and obstruction may also be present. Cryptorchidism is seen in males. The disorder can be inherited in an autosomal dominant or recessive manner, with consanguinity and occurrence in multiple siblings supporting recessive inheritance. Other common features include neuropathic bladder, constipation, slow growth rate, and electrocardiographic changes. Facial grimacing and urinary tract infections are also observed.", "CRANIOMETAPHYSEAL DYSPLASIA, AUTOSOMAL RECESSIVE": "Clinical features of the rare genetic disorder include: optic atrophy leading to blindness, prominent supraorbital ridges and hypertelorism, square profile face with prominent mandible, bilateral mixed hearing loss, mental retardation, widened ribs and metaphyses, diaphyseal hyperostosis in limb bones with mild metaphyseal widening, nasal flattening, relative macrocephaly, thick bony wedge over the bridge of the nose, depressed and flattened nasal bridge, secondary nasolacrimal duct obstruction, significant sclerosis of the skull base, difficulty breathing, but no loss of vision or hearing loss.", "SECKEL SYNDROME 4, Seckel syndrome": "Clinical features of this rare genetic disorder, known as Seckel syndrome, include dwarfism, small head, large eyes, beak-like nose, narrow face, and receding lower jaw. Mental retardation is less severe than expected. It is inherited in an autosomal recessive manner and can occur in both sexes. Some patients may have chromosome instability and hematologic problems. Seckel syndrome may also be associated with myelodysplasia and acute myeloid leukemia. Imaging studies of the central nervous system may show abnormalities. There is phenotypic overlap with type II microcephalic osteodysplastic primordial dwarfism. Cardiac malformations, such as tetralogy of Fallot, have been reported. Mutations in the ATR gene have been identified in some cases. Other features may include skeletal anomalies, abnormal gyration of the brain, and growth disorders of the nails. Immunologic defects and DNA repair factor abnormalities have also been observed.", "BARDET-BIEDL SYNDROME 2": "Clinical features of Bardet-Biedl syndrome include polydactyly, mental retardation, retinitis pigmentosa, obesity, hypogenitalism in males, renal hypoplasia, dilated cardiomyopathy, bicuspid aortic valve, secundum atrial septal defect, and kidney defects. Some affected individuals are shorter than their parents. The phenotype is similar in families with mutations at different loci, suggesting involvement of common biochemical pathways.", "3MC SYNDROME 1, 3MC syndrome": "Clinical features of Michels syndrome (also known as 3MC syndrome) include blepharophimosis, blepharoptosis, epicanthus inversus, cleft lip/palate, skeletal abnormalities, craniosynostosis, telecanthus, hearing loss, and developmental defects of the eye. Other characteristics may include spina bifida occulta, cranial asymmetry, abnormality of the occipital bone, radioulnar synostosis, short fifth finger, low-set ears, large anterior fontanel, accessory nipples, tuberous angioma, supraumbilical depression, small hands with bilateral short fifth fingers, broad feet, and severe axial hypotonia. Growth hormone deficiency and secondary hypogonadism may also be present in some cases. The disorder is believed to be a single recessive spectrum encompassing Michels, Malpuech, Carnevale, and OSA syndromes.", "FRAGILE X SYNDROME": "Clinical features of the rare genetic disorder include mental retardation, large testes, low-set large ears, asymmetric facial features, macroorchidism, characteristic facies, delayed language and motor development, unusual behavior, macrocephaly, dolichocephaly, normal intelligence in some carriers, irregular teeth, hypermobility of finger joints, extreme obesity, regional skin hyperpigmentation, delayed motor and speech development, hyperkinesis, autistic-like behavior, unilateral macroorchidism, mild to moderately severe mental retardation, and high psychiatric comorbidity.", "MEIER-GORLIN SYNDROME 1, Meier-Gorlin syndrome": "Clinical features of the rare genetic disorder, Meier-Gorlin syndrome, include microtia, absent patellae, micrognathia, camptodactyly, short stature, poor weight gain, and characteristic facial features. Other skeletal anomalies may include dislocation of the elbow, slender ribs and long bones, abnormal modeling of the glenoid fossas, and clinodactyly. Delayed bone age, joint hyperextensibility, and abnormal genitalia may also be present. Some patients may experience hearing loss, congenital labyrinthine anomalies, and mental retardation. Growth hormone deficiency and hernias may also occur.", "HAJDU-CHENEY SYNDROME": "Rare genetic disorder: Hajdu-Cheney syndrome. Clinical features include basilar impression, craniofacial and peripheral dysostosis, spinal osteoporosis, chondrodystrophy, acroosteolysis, multiple wormian bones, hypoplasia of ramus of mandible, osteoporosis with basilar impression, short stature, persistent cranial sutures, early loss of teeth, joint laxity, bathrocephaly, dislocations of the patella, hernia, micrognathia, narrow high palate, prominent ears, deep voice, shrinking fingers, mast cell abundance, dysmorphic face, joint hypermobility, open sutures of the skull, decreased bone density. Clinical features vary in number and severity, change over time, and progress with age.", "BOHRING-OPITZ SYNDROME": "Clinical features of the rare genetic disorder, Bohring-Opitz syndrome, include intrauterine growth retardation, cleft lip/palate, exophthalmos, retinal involvement, flexion deformities of the upper limbs, dislocation of radial heads, forehead hirsutism, failure to thrive, brain abnormalities, and facial anomalies such as bulging forehead, retrognathia, hypertelorism, and cleft/lip palate. Other characteristics may include hearing loss, seizures, and developmental delays. Variability in severity and overlap with other syndromes have been observed.", "BECKWITH-WIEDEMANN SYNDROME": "Macroglossia Hemimacroglossia Omphalocele Hemihypertrophy Hemihypertrophy of lower limb Hemihypertrophy of upper limb Hyperinsulinemic hypoglycemia Hyperinsulinemia Large for gestational age Nevus flammeus Nevus flammeus of the forehead Epidermal nevus Nevus Polyhydramnios Large placenta Abnormalities of placenta or umbilical cord Large placenta Abnormalities of placenta or umbilical cord Linear earlobe crease Diagonal earlobe crease Anterior creases of earlobe Postauricular pit Preauricular pit Posterior helix pit Supraauricular pit Nephroblastoma Hepatoblastoma Splenomegaly ", "APERT SYNDROME": "Apert syndrome is a rare genetic disorder characterized by skull malformation (acrocephaly), syndactyly (fusion) of the hands and feet, and fusion of bony structures. It is divided into typical and atypical forms based on the presence of a middigital hand mass with a single nail common to digits 2-4. Progressive synostosis occurs in various parts of the body, including the feet, hands, carpus, tarsus, cervical vertebrae, and skull. Crouzon disease, which shares some similarities with Apert syndrome, can be distinguished by the pattern of cervical fusion. Syndactyly severity in Apert syndrome is classified into three types, with the central three digits always being fused. The upper limb is typically more affected than the lower limb, and coalition of distal phalanges and synonychia is only found in the hands.", "GAPO SYNDROME": "The most crucial phenotype characteristics of the rare genetic disorder described in these texts include: frontal bossing, high forehead, midfacial hypoplasia, wide-open anterior fontanel, skeletal dysplasia, retarded bone age, cerebrovenous circulatory anomalies, dilated scalp veins, progeroid syndrome, glaucoma, keratoconus, hypogonadism, recurrent infections, alopecia, choanal stenosis, growth retardation, white eyelashes, deep furrows on sternum and back, disproportionate body build, severe glaucoma, band keratopathy, pseudoanodontia, papilledema, intracranial bruit, narrowing of sigmoid sinuses, optic atrophy, collagen fibers accumulation, extracellular pathologic collagenosis, short stature, large ears, depressed nasal bridge, prominent cheeks, thin lips, large tongue, unerupted teeth, micrognathia, large genitalia, dysmorphic craniofacial features, absence of facial pneumatization, maxillary and mandibular hypoplasia, ankylosis, cognitive defects, bone alterations, dilated cardiomyopathy, low IGF1 level, psychomotor retardation, craniofacial dysmorphism, vascular malformation, macrocephaly, hypertelorism, thickened eyelids, sparse eyebrows and eyelashes, depressed nasal bridge, long philtrum, thick lips, micrognathia, increased subcutaneous accumulations, keratopathy, myelinated retinal nerve fiber, glaucoma, central apnea, and respiratory insufficiency.", "MUCOLIPIDOSIS II ALPHA/BETA": "Mucolipidosis II is a rare genetic disorder with severe clinical features including dislocation of the hip, thoracic deformities, hernia, and hyperplastic gums. It is characterized by retarded psychomotor development, clear corneas, and restricted joint mobility. The condition, also known as I-cell disease, is caused by abnormal inclusions in fibroblasts. There is variability in age of onset, organ manifestation, and radiologic findings among affected individuals. Other symptoms may include pericardial effusion and brain atrophy. Biochemical studies show abnormal enzyme activity.", "SHORT SYNDROME": "Clinical features of the rare genetic disorder include Rieger anomaly, short stature, partial lipodystrophy, delayed dental eruption, delayed bone age, hyperextensibility of joints, midface hypoplasia, hypotrichosis, glucose intolerance, insulinopenic diabetes mellitus, lipoatrophy, delayed speech development, clinodactyly, congenital hip dislocation, iridocorneal abnormalities, megalocornea, progeria-like face, sensorineural hearing loss, nephrocalcinosis, microcornea, nystagmus, poor weight gain, macrocephaly, dysmorphic facial features, decreased subcutaneous fat, and cardiac anomalies. Other features include triangular face, deep-set eyes, small facial bones, narrow body build, absence of iridal stroma, and elevated intraocular pressure. Insulin resistance and diabetes are common, as well as sensorineural deafness and hyperextensibility of joints.", "COFFIN-SIRIS SYNDROME 2, Coffin-Siris syndrome": "Clinical features of the rare genetic disorder include mental retardation, absent or hypoplastic nails and terminal phalanx of the fifth finger, hypertrichosis, dysmorphic facial features, rough skin with hyperkeratotic plaques, broad feet and fingertips, thick and short corpus callosum, short stature, myopia, strabismus, coarse facies, behavioral abnormalities, limited language, hoarse or high-pitched voice, ventricular septal defect, patent ductus arteriosus, hip dislocation, muscular hypotonia, abnormal head shape, low-set and abnormally shaped ears, downslanting palpebral fissures, bulbous nasal tip, thin upper lip, teeth anomalies, brachydactyly or single palmar creases, developmental delay, hirsutism, frequent infections, severe speech delay, agenesis of the corpus callosum, sparse scalp hair, long eyelashes, seizures, ptosis, macroglossia, feeding and sucking problems, cardiac findings, and delayed bone age.", "COFFIN-LOWRY SYNDROME": "Clinical features of Coffin-Lowry syndrome (CLS) include mental retardation, pugilistic nose, large ears, tapered fingers, drumstick terminal phalanges, pectus carinatum, small stature, hypotonia, hypertelorism, anteverted nares, prominent frontal region, patulous lips, and large mouths. Other features include hydrocephalus, fullness of forearms, bulbous tapering fingers, puffy appearance of hands, kyphoscoliosis, proteodermatan sulfate storage, neurogenic weakness, calcification of ligamenta flava, myelopathy, sensorineural hearing deficit, premature exfoliation of primary teeth, depressive psychosis, drop episodes, premature death, progressive kyphoscoliosis, spinal stenosis, abnormalities in dentition, hearing loss, ocular abnormalities, and cognitive impairment. Brain abnormalities, such as decreased total brain volumes, altered neurodevelopment, and disruptions in neuronal organization, have also been observed. Clinical variability exists, with some individuals exhibiting milder features.", "VELOCARDIOFACIAL SYNDROME": "The del22q11 syndrome, also known as velocardiofacial syndrome (VCFS), is characterized by a wide range of clinical features. Common features include cleft palate, cardiac anomalies, typical facies, and learning disabilities. Other less frequent features include microcephaly, mental retardation, short stature, slender hands and digits, minor auricular anomalies, and inguinal hernia. VCFS is also associated with holoprosencephaly, tetralogy of Fallot, and hypoparathyroidism. Patients with VCFS often have characteristic facial dysmorphia, cardiac anomalies, ophthalmologic abnormalities, and frequent infections. They may also have T-lymphocyte dysfunction and a higher risk of developing psychiatric disorders, including schizophrenia. Growth parameters in patients with VCFS show weight deficiency in early childhood, weight normalization in later years, and development of obesity in adolescence. Intellectual disabilities, hypocalcemia, palatal anomalies, and cardiovascular anomalies are common in patients with VCFS. Neuropsychological features include blunt or inappropriate affect, severe psychiatric illnesses in adolescence, and a high rate of psychosis. Patients with VCFS may also have learning disabilities, behavioral problems, attention-deficit hyperactivity disorder (ADHD), and obsessive-compulsive disorder (OCD). VCFS is associated with an increased risk of autoimmune diseases, renal abnormalities, hearing deficits, and skeletal and ocular anomalies. The syndrome is caused by a deletion in the 22q11 region and can be inherited or occur as a result of de novo mutations.", "TRICHORHINOPHALANGEAL SYNDROME, TYPE I, TRICHORHINOPHALANGEAL SYNDROME, TYPE III, Trichorhinophalangeal syndrome": "Clinical features of the rare genetic disorder include sparse hair, beaked nose, long upper lip, severe metacarpophalangeal shortening, brachydactyly, cone-shaped epiphyses, low-set posteriorly rotated ears, prominent malar eminence and orbital ridge, bulbous nose, hypoplastic nasi alae nasi, hypotrichosis, long philtrum, wide halluces, flat arches, vertebral spondylosis, scoliosis, spondylolisthesis, osteophyte formation, osteopenia, secondary arthritic changes, and progressive osteopenia and osteoarthritis in older patients. Mental retardation and microcephaly are absent. The disorder can be differentiated from Ruvalcaba syndrome and trichorhinophalangeal syndrome. It is known as TRPS type III or Sugio-Kajii syndrome. Autosomal dominant and autosomal recessive inheritance patterns have been observed.", "LATERAL MENINGOCELE SYNDROME": "Clinical features of the rare genetic disorder include:\n- Generalized osteosclerosis\n- Distinctive craniofacial features (downslanting palpebral fissures, high-arched palate, mandibular and facial bone hypoplasia)\n- Multiple thoracic and lateral meningoceles\n- Enlarged sella turcica and optic foramina\n- Basilar impression and widened spinal cord\n- Scalloping of the posterior surfaces of the vertebral bodies\n- Short stature\n- Enlarged sella turcica\n- Thickened calvaria and prominent metopic sutures\n- Malar hypoplasia and wormian bones\n- Keloid formation and cryptorchidism in males\n- Hypoplastic posterior arch of the atlas\n- Connective tissue abnormalities\n- Hypertelorism, downslanting palpebral fissures, ptosis, and micrognathia\n- Chiari I malformation and dorsal extradural arachnoid cyst\n- Dural ectasia and multiple lateral meningoceles\n- Telecanthus, micrognathia, and inguinal hernias\n- Dolichocephaly, hypertelorism, high-arched palate, and scoliosis\n- Coarse hair, ptosis, posteriorly angulated ears, and nasal voice\n- Feeding difficulties, hypotonia, and dysmorphic features\n- Bicuspid aortic valve, sleep apnea, conductive hearing loss, and pectus excavatum\n- Scoliosis with expansion of the spinal canal and intervertebral foramina\n- Connective tissue defects\n- Acute back pain, urinary and stool incontinence, abnormal gait, and neuropathic pain.", "OPITZ GBBB SYNDROME, TYPE II": "Clinical features of the rare genetic disorder, Teebi syndrome, include hypertelorism, prominent forehead, arched eyebrows, broad nasal bridge, long philtrum, short stature, bicornuate uterus, umbilical defects, and congenital heart defects. Other features may include cleft lip/palate, central nervous system defects, and developmental delays. Males and females are equally affected, and there may be instances of male-to-male transmission. Mutations in the SPECC1L gene are associated with Teebi syndrome.", "COCKAYNE SYNDROME B": "Cockayne syndrome is a rare genetic disorder characterized by severe failure to thrive, mental retardation, congenital cataracts, loss of adipose tissue, joint contractures, distinctive facial features, kyphosis, and cachectic dwarfism. Other common features include sensorineural hearing loss, language impairment, inability to sit or walk independently, and early death. Patients have impaired DNA repair and increased sensitivity to radiation. Diagnosis is based on clinical features such as growth failure, microcephaly, cold extremities, abnormal brain imaging, weakness, hearing loss, photosensitivity, tremor, joint contractures, abnormal liver function, abnormal bowel movements, and cataracts. Early cataracts are associated with poorer prognosis. Metronidazole should be avoided due to the risk of acute hepatic failure. Phenotypic discordance between siblings is common.", "ACHONDROPLASIA": "Clinical features of this rare genetic disorder include short stature, long and narrow trunk, short extremities (especially in proximal segments), large head with frontal bossing, hypoplasia of the midface, trident configuration of the hands, hyperextensibility of joints (especially knees), limited extension and rotation at the elbow, thoracolumbar gibbus at birth, delayed motor milestones, normal intelligence (unless complications arise), caudad narrowing of interpediculate distance, notchlike sacroiliac groove, circumflex or chevron seat on metaphysis, megalencephaly, hydrocephalus, increased risk of intracranial bleeding, brainstem compression, risk of sudden unexpected death, respiratory dysfunction, obesity, tibial bowing, neurologic signs, middle ear disease, speech delay, orthodontic problems, ventricular shunt placement, cervicomedullary decompression surgery, cardiorespiratory and sleep dysfunction, jugular bulb dehiscence, acanthosis nigricans, increased mortality rate, and decreased life expectancy.", "TREACHER COLLINS SYNDROME 2, Treacher Collins syndrome": "Clinical features of the rare genetic disorder, possibly an autosomal recessive form of Treacher Collins syndrome, include downward-slanting palpebral fissures, coloboma of the lower lids, malar and mandibular hypoplasia, abnormal pinnae, conductive deafness, microtia, atresia of the external ear canal, dental anomalies, delayed-onset infantile cataracts, and additional anomalies involving the thyroid, thymus, heart, and genitalia. Phenotypic expression varies, and modifying factors may play a role. POLR1D mutations causing TCS2 exhibit similar features, but rare features reported in TCS1 are absent.", "FRONTOMETAPHYSEAL DYSPLASIA 1": "Clinical features of the rare genetic disorder include:\n- Extraordinarily marked frontal hyperostosis with prominent supraciliary ridges\n- Underdeveloped mandible\n- Cryptorchidism\n- Subluxated radial heads\n- Metaphyseal dysplasia resembling Pyle disease\n- Progressive contracture of fingers and lysis and fusion of carpal bones\n- Progressive osteosclerosis\n- Broad thumbs\n- Lack of molding of long bone shafts\n- Scoliosis\n- Limited wrist and elbow movement\n- Flexion deformities of fingers and ulnar deviation of wrists\n- Missing permanent teeth and retained deciduous teeth\n- Obstructive uropathy, subglottic stenosis, and tracheal web in some cases\n- Increased bone density, fused skull sutures, and flared metaphyses in neonates\n- Complications such as esophageal atresia, distal tracheoesophageal fistula, and respiratory distress\n- Severe progressive scoliosis, hearing loss, and urogenital anomalies in some cases\n- Prominent supraorbital ridges, hypertelorism, micrognathia, pectus carinatum, kyphoscoliosis, and contractures in fingers and toes\n- Thickened and sclerosed skull and facial bones with Erlenmeyer flask deformities in femurs\n- No extraskeletal manifestations in carrier mothers except for prominent supraorbital ridges.", "BIRK-BAREL SYNDROME": "Rare genetic disorder: mental retardation, hypotonia, dysmorphism, hyperactivity, feeding difficulties, dysphagia, muscle weakness, normal coordination/sensation, dysmorphic facial features (elongated face, narrow bitemporal diameter, flared eyebrows, downturned eyelids, high/narrow nasal bridge, short/broad/thick philtrum, micrognathia), speech abnormalities, joint contractures, pilonidal dimple/sinus, normal X-ray, normal mitochondria, axonal motor peripheral neuropathy, mild cerebellar syndrome, areflexia, tongue fasciculations, lagophthalmos, dysarthria, dysphonia, dysphagia, motor/speech delay, intellectual impairment, behavioral issues, seizures, sleep apnea, scoliosis, thin upper lip, microretrognathia, highly arched eyebrows.", "BARAITSER-WINTER SYNDROME 2, Baraitser-Winter syndrome": "Clinical features of the rare genetic disorder, Baraitser-Winter syndrome, include short stature, postnatal microcephaly, intellectual disability, hearing loss, seizures, trigonocephaly, hypertelorism, high-arched eyebrows, ptosis, iris or retinal coloboma, and lissencephaly. Other associated features include dysmorphic facial features, cleft lip and palate, congenital heart defects, renal tract anomalies, joint stiffness, and muscular involvement. There is phenotypic overlap with Fryns-Aftimos syndrome and Dubowitz syndrome.", "CROUZON SYNDROME": "Crouzon syndrome is a rare genetic disorder characterized by craniofacial dysostosis. Clinical features include cranial and facial manifestations, respiratory distress, exorbitism, midfacial retrusion, and neurosurgical complications such as hydrocephalus and tonsillar herniation. Phenotypic variability can include additional conditions like gonadal dysgenesis and short stature.", "PITT-HOPKINS SYNDROME": "Clinical features of Pitt-Hopkins syndrome include mental retardation, wide mouth, intermittent overbreathing, beaked nose, broad nasal bridge, clubbing of fingers and toes, pes cavus, microcephaly, dysmorphic facial features (such as thick lips and broad palate), abnormal breathing pattern, epilepsy, and intestinal problems. Other characteristics may include hypopigmented skin macules, high-grade myopia, and a hypoplastic corpus callosum. The onset of seizures and hyperventilation episodes is typically limited to the first decade of life. Some patients may have a milder phenotype with less severe intellectual disability and minor facial anomalies. Fetal pads on the fingers and toes can be a useful diagnostic feature. Not all mutations in the TCF4 gene cause the severe PTHS phenotype.", "BARAITSER-WINTER SYNDROME 1, Baraitser-Winter syndrome": "Clinical features of the rare genetic disorder include iris coloboma, bilateral ptosis, hypertelorism, broad nasal bridge, prominent epicanthal folds, short stature, mental retardation, craniofacial dysmorphism, edema, narrowing of the frontal part of the skull, arched eyebrows, trigonocephaly, hypertelorism with a broad root and bridge of the nose, large mouth with a fine upper lip and everted lower lip, prominent upper central incisors, posteriorly rotated hypoplastic ears, high-arched palate, short and broad neck, widely spaced hypoplastic inverted nipples, neonatal edema followed by significant weight loss, complex epilepsy, pachygyria, limited extension at knees and elbows, normal metabolic investigations and karyotypes, multiple craniofacial and skeletal dysmorphic features, bilateral frontal pachygyria, brachycephaly, wide forehead, hypertelorism, wide palpebral fissures with multiple eyelid colobomas, broad nasal root, long philtrum, macrostomia, prominent lips, high-arched palate, midline alveolar cleft, small and grooved chin, ear anomalies, structural anomaly of the corpus callosum, brachyacrocephaly, absent nasal tip, wide columella, carp-like mouth, submucous cleft of the soft palate, Dandy-Walker anomaly, gray matter heterotopia, brachycephaly, wide forehead, macroblepharon with eyelid colobomas, ectropion, depressed nasal tip, macrostomia, small and grooved chin, ear anomalies, structural anomaly of the corpus callosum, dilatation of the fourth ventricle, urogenital sinus, dysmorphic facial features, facial edema, temporal flattening, webbed neck, hypoplastic thorax with inverted nipples, limited extension of elbows and knees, epilepsy, severe mental retardation, diffuse pachygyria, short stature, microcephaly, intellectual disability, seizures, hearing loss, colobomata of the iris or retina, anterior-to-posterior gradient lissencephaly, reduction of shoulder girdle muscle bulk, progressive joint stiffness, muscular involvement, congenital arthrogryposis, cleft lip and palate, hallux duplex, congenital heart defects, renal tract anomalies, dysmorphic facial features with hypertelorism, broad nose, congenital nonmyopathic ptosis, ridged metopic sutures, sensorineural deafness, microcephaly, pachygyria, lissencephaly, reduction of shoulder girdle muscle bulk, progressive joint stiffness, intellectual disability, epilepsy, acute lymphocytic leukemia, cutaneous lymphoma, pleiotropic developmental disorder, feeding difficulties, growth retardation, microcephaly, intellectual disability, speech and motor delay, behavioral abnormalities, dystonia, pectus deformities, tracheoesophageal fistula, esophageal atresia, distal skeletal anomalies, hypertrichosis, excess skin, lytic lesions of the skull, atrial septal defect, sensorineural hearing loss, mild joint contractures, dysmorphic facial features, hypertelorism, wavy eyebrows, wide nose, wide mouth, prominent chin, phenotypic overlap with Dubowitz syndrome, microcephaly, dysmorphic facial features, low-set ears, ptosis, low anterior hairline, hypertrichosis, metopic ridging, asymmetric positioning of the globes, posteriorly rotated ears, broad nasal root, long columella, bifid uvula, limb anomalies, obsessive-compulsive behaviors, hyperactivity, myopia, optic nerve asymmetry, conductive hearing loss.", "FOCAL FACIAL DERMAL DYSPLASIA 3, SETLEIS TYPE, Focal facial dermal dysplasia": "Clinical features of Setleis syndrome include an aged leonine appearance, absent or multiple rows of eyelashes, slanted eyebrows, rubbery nose and chin, temporal marks, periorbital puffiness, flattened nasal bridge, redundant facial soft tissue, and normal growth and development. Some patients may also have imperforate anus, aberrant hair pattern, linear skin lesions, short palpebral fissures, cone-shaped teeth, pectus carinatum, and abnormal dermatoglyphic patterns. The syndrome has been reported in Puerto Rican, Japanese, Australian, English, German, and Mexican-American populations.", "NEURODEVELOPMENTAL DISORDER WITH IMPAIRED INTELLECTUAL DEVELOPMENT, HYPOTONIA, AND ATAXIA": "Phenotype characteristics of the rare genetic disorder described in the texts include global developmental delay, delayed walking, ataxic gait, hypotonia, hyporeflexia, poor or absent speech, dysmorphic features (such as pointed chin, downslanting palpebral fissures, high-arched palate, long face, long fingers, epicanthal folds, upturned nares, anteverted nares, prominent cheeks, small joint laxity), mild short stature, breath-holding spells, normal or slightly dysmorphic brain imaging, intellectual impairment, myopia and astigmatism, increased distractibility and hyperactivity, deficits in verbal and nonverbal reasoning, executive function, memory, receptive and expressive language, fine motor skills, and academic skills. Other features include multiple congenital anomalies (such as tracheoesophageal fistula with esophageal atresia, vertebral and rib anomalies, single kidney with hydronephrosis and hydroureter), shallow sulci, dysmorphic gyri, underdeveloped white matter, cavum septum pellucidum, syrinx, T2 hyperintensities in the periventricular corona radiata and putamen, fine motor delay, self-injurious behaviors, autism spectrum disorder, diminished white matter in the occipital lobes, enlarged Virchow-Robin spaces, hypoplastic splenium of the corpus callosum, spina bifida, cyclic vomiting, macrocephaly, frontal bossing, deep and widely set eyes, moderately enlarged lateral and third ventricles, and resolution of a Chiari malformation.", "DEVELOPMENTAL DELAY WITH SHORT STATURE, DYSMORPHIC FACIAL FEATURES, AND SPARSE HAIR": "Clinical features of the rare genetic disorder described in the texts include syndromic intellectual disability, delayed psychomotor development, unusual skull shape (scaphocephaly), short stature, hypertelorism, downslanting palpebral fissures, epicanthal folds, low-set ears, depressed nasal bridge, micrognathia, sparse hair of the scalp, eyelashes, and eyebrows. Brain imaging showed posterior malformations such as Dandy-Walker malformation, cerebellar vermis hypoplasia, and posterior fossa cyst. Other features included ventricular septal defect, renal anomalies, dysmorphic facial features, ectodermal dysplasia-like features, and developmental delays. Some patients had additional findings such as hematuria, proteinuria, dilated cardiomyopathy, and bony defects.", "SPASTIC PARAPLEGIA, INTELLECTUAL DISABILITY, NYSTAGMUS, AND OBESITY": "Phenotype characteristics: intellectual disability, dilated lateral ventricles, high growth percentiles, obesity, delayed speech, hypotonia, spastic paraplegia, poor visual acuity, nystagmus, dysmorphic features (brachyplagiocephaly, prominent forehead, full cheeks, deep-set eyes), reduced white matter bulk, delayed myelination, cerebral atrophy, partial agenesis of corpus callosum, developmental regression, language retardation, walking on tip-toes, lower limb hypertonia, pyramidal signs, mild global developmental delay, mild facial anomalies (short philtrum, ectropion of nostril, plump cheeks), abnormal corpus callosum, myelin defects, optic nerve dysplasia.", "BASILICATA-AKHTAR SYNDROME": "Rare genetic disorder: Neurodevelopmental disorder associated with point mutations in the MSL3 gene. Common features: Hypotonia, feeding difficulties, global delay in cognitive skills, motor milestones, and speech. Behavioral abnormalities, progressive spasticity, skeletal abnormalities, dysmorphic facial features. Brain imaging normal in most. Seizures, hearing loss, and retinal abnormalities observed in few. Developmental delay in all patients with varying severity. Autism spectrum disorder in 50%. Hypotonia, movement disorders, and seizures seen. MRI shows cerebellar vermis hypoplasia. Gastrointestinal, genitourinary, hearing, macrocephaly, and vision problems. Clinical management recommendations include referrals and regular follow-up.", "CHUNG-JANSEN SYNDROME": "1. Moderate gross motor delay, broad-based gait, severe speech delay, and intellectual disability.\n2. Dysmorphic features: straight eyebrows, strabismus, blepharophimosis, ptosis, long philtrum, and full lips. Tapered fingers and clinodactyly of fifth fingers, and long toes.\n3. Brain imaging was normal.\n4. Stereotypic behavior and anxiety.\n5. Slightly enlarged gyri and sulci and atypical large cavum septum pellucidum on brain MRI.\n6. Global developmental delay, intellectual disability, anxiety, hypotonia, poor balance, and obesity.\n7. Dysmorphic features: fleshy ears, small nose, deep-set eyes, short philtrum, micrognathia, round face, and upturned upper lip.\n8. Normal brain imaging.\n9. DIDOD associated with point mutations in the PHIP gene.\n10. Gross chromosomal abnormalities in two additional patients.\n11. Variable intellectual disability or learning difficulties, and behavioral problems such as autistic features, ADHD, anxiety, aggression, poor impulse control, and mood disorders.\n12. Dysmorphic features: high forehead, full eyebrows/synophrys, full fleshy ears, upturned nose with thick alae nasi, long philtrum, and thin lips.\n13. Additional features: hypotonia, easy fatigability, tapered fingers, clinodactyly, and skin syndactyly of the second and third toes.\n14. Variable features: high palate, hypertelorism, upslanting palpebral fissures, epicanthal folds, strabismus, cryptorchidism, joint hypermobility, cafe-au-lait spots, hypermetropia, and nystagmus.\n15. Most patients had normal brain imaging, but some had nonspecific mild abnormalities.", "COFFIN-SIRIS SYNDROME 1": "Rare genetic disorder: Coffin-Siris syndrome (CSS)\nPhenotype characteristics:\n- Mental retardation\n- Absent or hypoplastic fifth fingernails/toenails and phalanx\n- Hypertrichosis (excessive hair growth)\n- Dysmorphic facial features (low anterior hairline, thick arched eyebrows, broad nose, thick lips)\n- Rough skin with hyperkeratotic plaques\n- Broad feet and fingertips\n- Short stature\n- Behavioral abnormalities (obsessive-compulsive disorder, withdrawal, stubbornness, autistic features)\n- Limited language with hoarse or high-pitched voice\n- Mild nail hypoplasia\n- Coarse facies\n- Additional features: myopia, strabismus, mild short stature, nail hypoplasia, ventricular septal defect, patent ductus arteriosus, coarctation of the aorta, hip dislocation, muscular hypotonia, abnormal head shape, low-set and abnormally shaped ears, downslanting palpebral fissures, bulbous nasal tip, thin upper lip, minor teeth anomalies, brachydactyly or single palmar creases, frequent infections, agenesis of the corpus callosum, severe speech delay, intellectual disability.", "COFFIN-SIRIS SYNDROME 2": "Clinical features of the rare genetic disorder include developmental delay, abnormal corpus callosum, absent/hypoplastic fifth finger/toenails, sparse scalp hair, long eyelashes, coarse facial appearance, wide mouth, thick lips, and abnormal ears. Other characteristics include feeding and sucking problems, frequent infections, cardiac findings, short stature, and absent/hypoplastic fifth phalanx of hands and feet. Additional features include low frontal hairline, thick and arched eyebrows, ptosis, low-set ears, thin upper and full lower vermilion borders, flat nasal bridge, broad nose, large mouth, macroglossia, brachytelephalangy, nail hypoplasia, delayed bone age, hypotonia, seizures, and agenesis of the corpus callosum. Chromosome 1p36.11 microduplication syndrome is characterized by microcephaly, impaired intellectual development, delayed motor milestones, hand and foot anomalies, growth impairment, constipation, frequent airway infections, dysmorphic facial features, stereotypies, and distinctive feet with brachydactyly and shortening and medial deviation of the great toes.", "COFFIN-SIRIS SYNDROME 4": "Coffin-Siris syndrome: developmental delay, hypotonia, microcephaly, seizures, Dandy-Walker malformation, vision and hearing problems, absent/hypoplastic fifth nails, hirsutism, sparse scalp hair, thick eyebrows, long eyelashes.", "COFFIN-SIRIS SYNDROME 5": "Coffin-Siris syndrome (CSS) is characterized by delayed psychomotor development, intellectual disability, absent speech, poor overall growth, short stature, microcephaly, and dysmorphic facial features. These features include coarse facies, low frontal hairline, thick eyebrows, long eyelashes, flat nasal bridge, broad nose with thick anteverted nares, large mouth, thick lower vermilion, short philtrum, abnormal ears, and sparse scalp hair. Other features may include hypoplasia of distal phalanges with nail hypoplasia, atrial septal defect, dextropositio cordis, small cerebellum, Dandy-Walker malformation, abnormal corpus callosum, feeding difficulties, and congenital heart defects. Some patients may also have seizures.", "BAINBRIDGE-ROPERS SYNDROME": "Clinical features of the rare genetic disorder described in the texts include severe psychomotor retardation, feeding problems, severe postnatal growth retardation, arched eyebrows, anteverted nares, ulnar deviation of the hands, hypotonia, developmental delay, absent speech, poor or absent independent walking, dysmorphic features such as downslanting palpebral fissures and broad nasal bridge, loss of white matter in the brain, thin corpus callosum, relative microcephaly, intellectual disability, delayed walking, nonverbal communication, autistic features, seizures, sleep problems, prominent forehead, hypertelorism, strabismus, high-arched eyebrows, long tubular nose, high-arched palate, crowded teeth, marfanoid habitus with arachnodactyly, tall stature, pes planus, scoliosis, and minor abnormalities on brain imaging.", "NOONAN SYNDROME 4": "Noonan syndrome caused by SOS1 gene mutation has distinct features: more pulmonic stenosis, less atrial septal defect, ectodermal manifestations (keratosis pilaris, curly hair), macrocephaly, rare mental retardation. SOS1 mutation patients have higher prevalence of keratosis pilaris, curly hair, and ocular ptosis compared to PTPN11 mutation patients. Facial dysmorphisms, prenatal anomalies, and moderate pulmonic stenosis are common in newborns with SOS1 mutation. NS4 patients have variable phenotypic expression, including suggestive facial characteristics, pectus excavatum, ptosis, sparse eyebrows, intellectual and motor delays, and sensorineural hearing loss. No short stature, lymphatic dysplasia, cryptorchidism, skin findings, or congenital heart disease.", "NEURODEVELOPMENTAL DISORDER WITH SPEECH IMPAIRMENT AND DYSMORPHIC FACIES": "Patients with the rare genetic disorder described in the texts exhibit a range of neurodevelopmental and physical characteristics. These include global developmental delay, mild motor delay, impaired intellectual development, learning difficulties, poor speech and language acquisition, and speech apraxia. Many patients also display behavioral or psychiatric abnormalities, dysmorphic facial features, distal limb anomalies, and additional features such as gastrointestinal problems, recurrent infections, and visual impairment. Some patients experience seizures or have nonspecific brain imaging findings. Clinical variability is observed, with one patient specifically presenting with speech delay and childhood apraxia of speech. A genetic mutation in the SETD1A gene was identified in one patient.", "SHPRINTZEN-GOLDBERG CRANIOSYNOSTOSIS SYNDROME": "Clinical features of the rare genetic disorder, Shprintzen-Goldberg syndrome (SGS), include craniosynostosis, severe exophthalmos, maxillary and mandibular hypoplasia, soft tissue hypertrophy of the palatal shelves, low-set ears, multiple abdominal hernias, arachnodactyly, camptodactyly, infantile hypotonia, developmental delay, mental retardation, obstructive apnea, pectus carinatum or excavatum, bowing of long bones, flare of the metaphyses, large anterior fontanel, 13 pairs of ribs, distinct vertebral abnormalities, progressive osteopenia, communicating hydrocephalus, choanal atresia and stenosis, intestinal malrotation, cranial asymmetry, hypotonia, osteopenia, hydrocephalus, dysmorphic facial features, foot deformities, myopia, delayed puberty, and lack of subcutaneous fat. SGS is likely a generalized connective tissue dysplasia. It is important to differentiate SGS from other syndromes with similar features. Some cases may be misdiagnosed.", "CHITAYAT SYNDROME": "Clinical features of the rare genetic disorder include: diffuse bronchomalacia, facial dysmorphism (box-shaped skull, hypertelorism, depressed nasal bridge, midface hypoplasia, retrognathia), digital anomalies (short middle fingers, extra bone on index fingers, clinodactyly, proximal insertion of thumbs, syndactyly, overlapping fingers), skeletal abnormalities (hyperphalangism, dysplasia of phalanges, delayed ossification of carpal bones, hallux valgus), respiratory distress (requiring assisted ventilation, recurrent infections), pectus excavatum, and polyhydramnios.", "GLOBAL DEVELOPMENTAL DELAY, ABSENT OR HYPOPLASTIC CORPUS CALLOSUM, AND DYSMORPHIC FACIES": "Rare genetic disorder: Intellectual disability syndrome with respiratory insufficiency, hypotonia, feeding problems. Dysmorphic features: small fontanel, flat occiput, coarse square-shaped face, broad nasal bridge, wide-set eyes, retrognathia, upturned nose, prominent columella, long smooth prominent philtrum, narrow palate, widely spaced inverted nipples, talipes equinovarus. Delayed psychomotor development, poor expressive speech, intellectual disability. Common dysmorphic features: short stature, triangular/oval face, pointed chin, epicanthal folds, wide-set eyes, smooth/deeply grooved philtrum, prominent columella, wide mouth, abnormally shaped ears. Other features: microcephaly, growth hormone deficiency, hyperopia, feeding problems, renal/cardiac anomalies, absence/hypoplastic corpus callosum.", "NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA, SEIZURES, AND ABSENT LANGUAGE": "Text 1: A boy with severe developmental delay, absent speech, epilepsy, encephalopathy, hypotonia, dystonia/dyskinesia, and macrocephaly. Brain imaging showed cerebral atrophy, enlarged ventricles, and white matter abnormalities. Mutation in HECW2 gene.\n\nText 2: 7 patients with a severe neurodevelopmental disorder. Hypotonia, severely delayed psychomotor development, and absent language. Abnormal behaviors, autistic features, and seizures observed. Dysmorphic features include prominent forehead, midface retrusion, strabismus, and wide mouth with high-arched palate. Brain imaging showed cerebral atrophy and enlarged ventricles.", "ARTHROGRYPOSIS, DISTAL, TYPE 2B1": "Clinical features of the rare genetic disorder, designated DA2B, include triangular face, downslanting palpebral fissures, attached earlobes, prominent nasolabial folds, small mouth, small mandible, arched palate, cervical webbing, short stature, severe camptodactyly, ulnar deviation, and vertical talus and/or talipes equinovarus. The disorder differs from DA2A (Freeman-Sheldon syndrome) as it lacks feeding difficulties at birth or surgical revision of the mouth. Other families with DA2B also exhibited camptodactyly, ulnar deviation, vertical talus, talipes equinovarus, small mouth, prominent nasolabial folds, small chin, triangular face, facial asymmetry, hypertelorism, high nasal bridge, malar hypoplasia, micrognathia, highly arched palate, notched chin, posteriorly angulated ears, cleft lip and palate, ptosis, webbed neck, kyphoscoliosis, and short stature. Some individuals with DA2B had trismus, congenital contractures in the hands and feet, congenital hip dislocation, proximal joint contractures, short neck muscles, thin calves, camptodactyly, mildly increased serum creatine kinase, myopathic changes in muscle biopsies, narrow palpebral fissures, limited mouth opening, and a heterozygous mutation in the TNNI2 gene. Another family with DA2B exhibited bilateral and symmetric congenital contractures of the distal limbs, camptodactyly, planovalgus, lateral rotation of the big toes, small mouth, prominent nasolabial folds, downslanting palpebral fissures, and blepharophimosis. Although initially diagnosed with Freeman-Sheldon syndrome (DA2A), molecular analysis confirmed a diagnosis of DA2B1.", "FACIAL DYSMORPHISM, HYPERTRICHOSIS, EPILEPSY, INTELLECTUAL/DEVELOPMENTAL DELAY, AND GINGIVAL OVERGROWTH SYNDROME": "Three unrelated children with a neurodevelopmental syndrome were studied. Patient 1 had delayed milestones, patient 2 had motor and language delays, and patient 3 had mildly delayed milestones. All had generalized hypertrichosis and a distinct facial appearance. Other features included nystagmus, hypotonia, hyperreflexia, and seizures. Patient 1 had abnormal EEG and brain imaging showed thin corpus callosum and enlarged ventricles. Patient 2 had a developmental index of 85 and patient 3 had brachydactyly and hip dysplasia.", "CLEFT PALATE, CARDIAC DEFECTS, AND MENTAL RETARDATION": "Clinical features of the rare genetic disorder include: congenital heart defects (atrial septal defect, Fallot pentalogy, ventricular septal defects), cleft lip/palate, short stature, microcephaly, distally-placed thumbs, short second and fifth fingers, long and broad first toes, wide distance between first and second toes, medial dorsal curvature of the fourth toes with syndactyly of the second and third toes. Other features include delayed motor development, learning difficulties, overlapping facial features (broad forehead, finely arched eyebrows, mildly shortened philtrum, tented upper lip), dysmorphic facial features (arched and laterally extended eyebrows, mildly upslanting palpebral fissures, deeply set eyes, bitemporal narrowing, thin upper vermilion, full lower vermilion), feeding problems, skeletal anomalies, and intellectual disability. Some patients may also have autism spectrum disorder, hearing loss, short stature, hypotonia, failure to thrive, and gastrointestinal, skeletal, limb, and skin abnormalities.", "BARTSOCAS-PAPAS SYNDROME 1": "Clinical features of Bartsocas-Papas syndrome include popliteal pterygium, synostosis of hand and foot bones, digital hypoplasia, syndactyly, facial clefts, ankyloblepharon, filiform bands between the jaws, absent eyebrows and eyelashes, hypoplastic nose, cleft lip and palate, nail hypoplasia, cutis aplasia, widely spaced nipples, low-set umbilicus, renal hypoplasia, omphalocele, aplasia of the urethra, ectropion, micrognathia, short neck, asymmetric nipples, anal stenosis, rectal polyp, hypoplastic labia majora, and various skeletal abnormalities. The disorder is often lethal, but some cases have survived beyond the neonatal period. The syndrome is more common among individuals of Mediterranean and Arab ancestry. Autosomal recessive inheritance is likely.", "ABLEPHARON-MACROSTOMIA SYNDROME": "Clinical features of the rare genetic disorder include absent eyelids, eyebrows, and eyelashes, fusion defects of the mouth, rudimentary external ears, ambiguous genitalia, absent or rudimentary nipples, coarse and dry skin with redundant skin folds, delayed development of expressive language, absence of zygomatic arches, failure of lip fusion resulting in an enlarged fish-like mouth, abnormally shaped ears and nose, absence of lanugo, ventral hernia, vestigial eyelid structures, shallow orbits with inadequate eyelids, hypertelorism, large square mouth, protrusion of maxilla, malformed low-set ears, wrinkled and hairless skin, ambiguous genitalia, shortness of the eyelids, low nasal bridge with hypoplastic and anteverted nostrils, macrostomia, small ears, absence of nipples, absence of lanugo, absence of hair, brows, and lashes, macrostomia, ear anomalies, redundant skin, abnormal genitalia, visual problems, hearing loss, poor hair growth, finger contractures, growth retardation, mild developmental impairment, absence of scalp hair, eyelids, eyebrows, or eyelashes, camptodactyly, syndactyly of fingers 2 to 5, distinctive clinical manifestations shared with Barber-Say syndrome, ablepharon in AMS versus ectropion in Barber-Say syndrome, marked hypertrichosis in Barber-Say syndrome, severe genital abnormalities in AMS, absent eyelashes and eyebrows, vertical shortening of upper and lower eyelids, abnormal ears with rudimentary cartilage, alae nasi and malar hypoplasia, absent zygomatic arches, small chin, chin and breast hypoplasia, partial cutaneous syndactyly with camptodactyly, high frequency hearing loss, normal developmental milestones and intelligence, harlequin-shaped eyebrows, hypoplastic nasal dorsum, absent columella, hypoplastic ala nasi, macrostomia, CL II malocclusion, conical teeth, long uvula, deficient lateral development of the vermilion border, thin and disrupted elastic fibers, abnormal collagen patterns.", "CEREBELLAR, OCULAR, CRANIOFACIAL, AND GENITAL SYNDROME": "Rare genetic disorder: \n- Absence of scrotum and labia majora\n- Bilateral undescended testes\n- Agenesis of the scrotum\n- Complete agenesis of the labia majora\n- Visual impairment\n- Moderate hearing loss\n- Dysmorphic features\n- Cognitive impairment\n- Corneal dystrophy\n- Microcephaly\n- Distinctive facial features (short forehead, laterally extended, medially flared eyebrows)\n- Central corneal opacities\n- Underdevelopment of labioscrotal folds\n- Nonprogressive pontocerebellar hypoplasia\n- Hair extruding from lactiferous ducts\n- Dandy-Walker malformation\n- Global developmental delay", "INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC 34": "Phenotype characteristics of the rare genetic disorder include: \n- Syndromic form of intellectual disability\n- Delayed psychomotor development\n- Poor nasal speech\n- Slender build\n- Scoliosis or kyphosis\n- Pes planus\n- Ankylosis of the metacarpophalangeal joint of P1\n- Macrocephaly\n- Long face with upslanting palpebral fissures\n- Malar hypoplasia\n- Thin and high nasal root\n- Small open mouth\n- Narrow high-arched palate with dental crowding\n- Variable features such as strabismus, myopia, and hypotonia\n- Seizures and delayed puberty in some cases\n- Brain imaging abnormalities including thickening or dysgenesis of the corpus callosum, Chiari type I malformation, and hypoplastic cerebellum\n- Developmental delay\n- Left ventricular noncompaction (LVNC)\n- Autism and mild intellectual disability\n- Aggressive behavior\n- Dysmorphic features such as long face, prominent nose, wide mouth, thick lips, and short philtrum\n- General hypotonia\n- Increased patellar and Achilles reflexes without clonus\n- Kyphoscoliosis and bilateral hallux valgus\n- Corpus callosum defects in some cases\n- Dilated cardiomyopathy with LVNC and Ebstein anomaly\n- Prenatal onset of growth failure with preservation of head circumference\n- Failure to thrive, feeding intolerance, and silent tracheal aspiration\n- Global developmental delay\n- Mild pseudobulbar palsy\n- Dilated left ventricle with myocardial noncompaction, Ebsteinoid tricuspid valve tethering, and patent foramen ovale\n- Exotropia, severe mixed central and obstructive sleep apnea, and fungal esophagitis\n- Dysmorphic features including triangular face, widely spaced eyes, downslanting palpebral fissures, malar flattening, and thin vermilion of the upper lip\n- Brain imaging abnormalities including thick genu of the corpus callosum, mild Arnold Chiari I malformation, and flattened pituitary gland.", "TRICHORHINOPHALANGEAL SYNDROME, TYPE I": "Clinical features of the rare genetic disorder described in the texts include thin and slowly growing hair, pear-shaped nose with high philtrum, brachyphalangy with finger deformation and wedge-shaped epiphyses. Other characteristics include supernumerary incisors, pseudo-pseudohypoparathyroidism, low-set posteriorly rotated ears, prominent malar eminence and orbital ridge, bulbous nose, hypoplastic nasi alae nasi, hypotrichosis, long philtrum, brachydactyly, wide halluces, flat arches, vertebral spondylosis, scoliosis, spondylolisthesis, shortening of phalanges, osteophyte formation, osteopenia, secondary arthritic changes, and cone-shaped epiphyses. The disorder shows clinical variability and can present with early-onset slowly progressive spastic paraplegia, dysarthria, low-normal intellectual capacity, and skeletal abnormalities of the hands and feet. The disorder is caused by mutations in the SACS gene and TRPS1 gene, resulting in autosomal recessive spastic ataxia-6 and type I trichorhinophalangeal syndrome, respectively.", "NEURODEVELOPMENTAL DISORDER WITH CENTRAL AND PERIPHERAL MOTOR DYSFUNCTION": "1. Neurodevelopmental disorder with various clinical features: generalized hypertonia, stridor, poor feeding, global developmental delay, hyperreflexia, small head circumference, no purposeful movements, poor overall growth, no social smile, babbling, dysmorphic features (hypertelorism, high and broad nasal bridge, micrognathia, glossoptosis, cleft palate, long thin hyperextensible fingers, 11 pairs of ribs), diffuse white matter T2 hyperintensities on brain imaging, high mortality rate.\n\n2. Severe neurologic disorder: polyhydramnios, respiratory insufficiency, severe hypotonia, amimia, contractures of hands and feet, absence of reflexes, no reaction to touch or pain, no eye contact, narrow symmetric pupils, seizures, normal brain and spinal cord imaging.\n\n3. Developmental delay, delayed walking, wide-based ataxic gait, cerebellar signs (dysarthria, intention tremor, dysmetria, saccadic pursuits, dysdiadochokinesia), progressive spastic hypertonia with hyperreflexia, clonus, extensor plantar responses, myoclonic jerks, mild intellectual disability, aggression, anxiety, cerebellar atrophy, diffuse T2 hyperintensities suggesting hypomyelination, decreased central motor nerve conduction velocities, decreased somatosensory evoked potentials, length-dependent demyelinating sensorimotor peripheral neuropathy.", "DCPS": "Text 1: Delayed psychomotor development, microcephaly, congenital hypotonia, severe growth delay, dysmorphic facial features, joint laxity, brachydactyly, sandal gap, skin hypopigmentation, atrial septal defects. Normal brain imaging.\n\nText 2: Delayed psychomotor development, intellectual disability, absent speech, possible prominent upper jaw, microcephaly, severely delayed motor development, hypotonia, normal brain imaging, no abnormalities of skin, hair, joints, vision, or hearing.\n\nText 3: Mutation in the DCPS gene, below 3rd centile for height, weight, and head circumference, respiratory distress, atrial septal defect, feeding intolerance, recurrent respiratory infections, sleep apnea, growth delay, psychomotor delay, reduced subcutaneous tissue, hypotrophic muscle mass, dysmorphic facial features, short neck, brachydactyly, fifth finger clinodactyly, blond hair, pigmentary skin anomalies along Blaschko lines.", "KENNY-CAFFEY SYNDROME, TYPE 1": "Kenny-Caffey syndrome is a rare genetic disorder with autosomal recessive inheritance. Clinical features include generalized hypertonic seizures, hypocalcemia, neonatal hypoparathyroidism, short stature, and intelligence. Other characteristics include cortical thickening and medullary stenosis. Growth retardation, craniofacial anomalies, small hands and feet, and absent diploic space in the skull are also observed. Psychomotor retardation and absence of macrocephaly are common.", "ANDERSEN CARDIODYSRHYTHMIC PERIODIC PARALYSIS": "Clinical features of Andersen syndrome include potassium-sensitive periodic paralysis, ventricular ectopy, and dysmorphic features. Dysmorphic features may include short stature, low-set ears, hypoplastic mandible, clinodactyly, and scoliosis. Cardiac manifestations can include a variable prolongation of the QT interval, ventricular bigeminy, and short runs of bidirectional ventricular tachycardia. Other features may include cleft palate, hyperthyroidism, and mild dysmorphic features. Mutations in the KCNJ2 gene have been identified in individuals with Andersen syndrome. Dental and skeletal anomalies, such as delayed eruption of permanent dentition and hand and foot size at the lower limits of normal, may also be present.", "ACRODYSOSTOSIS 1 WITH OR WITHOUT HORMONE RESISTANCE": "Acrodysostosis is a rare genetic disorder characterized by small hands and feet, peculiar facies including short nose, open mouth, and prognathism. Other common features include cone-shaped epiphyses, mental deficiency, nasal hypoplasia, peripheral dysostosis, blue eyes, and advanced skeletal maturation. Epiphyseal stippling is a consistent radiologic feature. Hormone resistance and endocrine abnormalities are also observed. Different mutations in PRKAR1A and PDE4D genes result in distinct phenotypes, with PRKAR1A mutations associated with hormone resistance, normal intellect, and no facial dysostosis, while PDE4D mutations are linked to characteristic facial features, intellectual disability, and lack of hormone resistance. Developmental disabilities and spinal stenosis are common in both groups.", "ARTHROGRYPOSIS MULTIPLEX CONGENITA 2, NEUROGENIC TYPE": "Rare genetic disorder characterized by arthrogryposis-like symptoms, including flexion contractures at elbows and knees. No hip dislocation observed. In an inbred Arab group, 23 cases were found, later increasing to 40. Congenital heart defects limited to one sibship. Neurologic examination revealed a neuropathic type of arthrogryposis. Common clinical features include flexion contractures of elbows and knees, marked equinovarus. Incomplete penetrance in females. Autopsies showed depletion of spinal motor neurons and absence of muscle spindles.", "BARBER-SAY SYNDROME": "Rare genetic disorder: Barber-Say syndrome. Clinical features include macrostomia, ectropion, atrophic skin, marked hypertrichosis, growth retardation, psychomotor retardation, ocular hypertelorism, thin lips, abnormal auricles and nose, redundant facial skin, hypoplastic nipples, and delayed tooth eruption. Features resemble Cornelia de Lange syndrome. Inheritance may be autosomal dominant or X-linked. Distinguishing features from ablepharon-macrostomia syndrome include ectropion and marked hypertrichosis. Skin biopsy shows atrophic epidermis and reduced elastic fibers. Dental abnormalities and gingival fibromatosis may be present. Considered an ectodermal dysplasia.", "COFFIN-SIRIS SYNDROME 11": "Summary: This study describes a rare neurodevelopmental disorder in five unrelated children. Common features include global developmental delay, delayed walking, intellectual impairment, speech and language delay, and dysmorphic features such as sparse hair, low hairline, and external ear malformations. Other characteristics include prenatal concerns, visual impairment, feeding difficulties, and small hands and feet. The most severely affected patient had additional features consistent with Coffin-Siris syndrome.", "KEIPERT SYNDROME": "Keipert syndrome is characterized by sensorineural deafness, abnormal facies (especially nose), broad thumbs, and broad phalanges. Other features include depressed nasal bridge, prominent frontal bones, hypoplastic maxilla, mild pulmonic stenosis, hoarseness, and cognitive impairment. Mutations in the GPC4 gene have been identified in some cases. Fibrous dysplasia of the sphenoid sinus and conductive hearing loss have been reported in a few patients. Autism or autistic features may also be present. Deafness appears to be relatively infrequent in Keipert syndrome.", "NOONAN SYNDROME 1": "Noonan syndrome is characterized by various clinical features including webbing of the neck, coarctation of the aorta, cryptorchidism, pterygium colli, deformed sternum, myocardiopathy, pulmonary stenosis, patent ductus arteriosus, elevated alkaline phosphatase levels, seizures, anomalous upper lateral incisors, lymphedema, posterior cervical hygroma, cutaneous lymphangioma, craniofacial anomalies, hypertrophic cardiomyopathy, short stature, headache, Arnold-Chiari malformation, ECG abnormalities, congenital heart defects, and motor performance impairments.", "INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC, HACKMANN-DI DONATO TYPE": "This study describes a rare X-linked intellectual developmental disorder in 10 male patients. They presented with global developmental delay, delayed walking, impaired intellectual development, and speech delay. Most had behavioral abnormalities such as ADHD or aggression. Patients had a marfanoid body habitus with tall stature, long face, slender limbs, joint laxity, arachnodactyly, and camptodactyly. Dysmorphic features included short philtrum, midface hypoplasia, open mouth appearance, and prominent ears. Cardiac anomalies, cryptorchidism, hypospadias, and micropenis were also observed.", "CSNK1G1": "Rare genetic disorder: Mutation in serine/threonine kinase gene leads to non-syndromic early-onset epilepsy. Encoded kinase phosphorylates acidic proteins like caseins and Claspin, involved in cell cycle checkpoint arrest in response to stalled replication forks.", "OHDO SYNDROME, X-LINKED": "Text 1: Patient 2 had low weight, blepharophimosis, ptosis, broad and depressed nasal bridge, long flat philtrum, thin vermilion, microstomia, micrognathia, cryptorchidism, scrotum hypoplasia, joint hyperextensibility, clinodactyly, overriding third toes, cafe-au-lait spots, developmental delay, deafness, and feeding problems. Diagnosed with Ohdo blepharophimosis syndrome.\n\nText 3: Maternal nephew had a similar phenotype and died of metastatic carcinoma. Classified as a distinct blepharophimosis-mental retardation syndrome, MKB type, with X-linked inheritance. Phenotype in adulthood had coarse facial features, thick alae nasi, triangular face, and a different gestalt from SBBYS type.\n\nText 2: 3 sibs with impaired intellectual development, characteristic facial features, and distal extremity anomalies. One had tetralogy of Fallot, bronchiectasis, pneumonia, recurrent otitis media, global developmental delay, short stature, microcephaly, short palpebral fissures, small mouth, low B-cell and T-cell proliferation, low IgG levels, and low antibody titers. Other sibs had otitis media, low B-cell count, low antibody titers, and atrioventricular canal defect with pulmonic stenosis. Blepharophimosis and blepharitic keratopathy in some patients.", "INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC, CLAES-JENSEN TYPE": "Clinical features of the rare genetic disorder include severe mental retardation, slowly progressive spastic paraplegia, facial hypotonia, maxillary hypoplasia, aggressive behavior, strabismus, epileptic seizures, short stature, microcephaly, hypermetropia, small feet, dysmorphic facial features, small testes or penis, overfriendly and anxious character, large ears with raised lobes, big hands with large fingers and proximal thumbs, prominent and separated superior incisors, scrotal tongue, pectus excavatum, poor speech, low weight, high palate, mild cognitive impairment, motor delay, severe language delay, intellectual impairment, developmental delay, round face, high forehead, downslanting palpebral fissures, low columella, short philtrum, thin lips, obesity, hypothyroidism, primary amenorrhea, mild hypertrichosis, learning difficulties, impaired intellectual development, behavioral disorders, hypotonia, memory difficulties, epilepsy, and features of autism.", "MEGALENCEPHALY-CAPILLARY MALFORMATION-POLYMICROGYRIA SYNDROME": "Clinical features of the rare genetic disorder, megalencephaly-cutis marmorata telangiectatica congenita (MCMTC), include abnormalities of somatic growth, facial features, brain, and connective tissue. Common characteristics include cutis marmorata, nevus flammeus, cavernous hemangiomas, asymmetric growth pattern, central nervous system malformations, and neurologic abnormalities. Other features may include macrocephaly, hemifacial and segmental overgrowth, macrosomia, and visceral and subcutaneous cavernous hemangiomas. Additional findings include poor clinical outcomes, growth failure, arrhythmia, structural cerebral abnormalities, cerebellar tonsillar herniation, ventriculomegaly, abnormal cortical morphogenesis, and various vascular anomalies. Some patients may have normal functioning or minor problems, particularly if there are no structural brain anomalies. There may be an overlap with megalencephaly, polymicrogyria-polydactyly hydrocephalus syndrome (MPPH), and the term MPPH-CM has been proposed. Growth hormone deficiency and other endocrine abnormalities may also be present in some cases.", "NOONAN SYNDROME 2": "Autosomal recessive Noonan syndrome: average to large birth length and head circumference, developmental delay in some patients, congenital heart defects or valve disease in most patients, variable facial features (low-set ears, broad short neck), leukemia in some families, prenatal presentation with polyhydramnios, cystic hygroma, and/or arthrogryposis, neonatal deaths, rarely reported cryptorchidism.\n\nAutosomal recessive Noonan syndrome with hypertrophic obstructive cardiomyopathy: typical Noonan syndrome phenotype, hypertrophic obstructive cardiomyopathy at birth, improvement or deterioration of the defect over time, more frequent than in autosomal dominant Noonan syndrome.\n\nNoonan syndrome 2: distinctive facial features suggestive of Noonan syndrome, hypertrophic cardiomyopathy, 5th brachymetapody, mild intellectual disability.", "ALAZAMI SYNDROME": "Rare genetic disorder: Alazami syndrome\n- Facial dysmorphism: malar hypoplasia, deep-set eyes, broad nose, short philtrum, macrostomia\n- Severely impaired intellectual development\n- Primordial dwarfism: growth parameters 3.5 SD below mean\n- Skeletal findings: scoliosis, mild epiphyseal changes, no dysplasia\n- Normal laboratory investigations: plasma amino acids, acylcarnitines, urine organic acids, very long-chain fatty acids, CBC, renal profile, bone profile\n- Brain imaging: normal or mild cortical thickening\n- Other features: failure to thrive, poor overall growth, short stature, developmental delay, involuntary hand movements, poor speech, poor balance, hypersensitivity to touch and sound, anxiety\n- Additional features in some patients: disproportionately mild microcephaly, thickened skin over hands and feet, stereotypic hand wringing, scoliosis", "SCHUURS-HOEIJMAKERS SYNDROME": "Clinical features of Schuurs-Hoeijmakers syndrome (SHMS) include distinctive facial appearance (arched eyebrows, long eyelashes, hypertelorism, downslanting palpebral fissures), intellectual impairment, delayed psychomotor development, poor speech, hypotonia, congenital anomalies (cardiac defects, eye abnormalities), feeding difficulties, delayed motor development, seizures, brain abnormalities (cerebellar hypoplasia, ventriculomegaly), kidney abnormalities, cryptorchidism, behavioral difficulties, and autistic features. Overgrowth, clinodactyly, camptodactyly, persistent ductus arteriosus, patent foramen ovale, bicuspid aortic valve, seizures, ataxia, and decreased complement factor C3 were also observed in some patients. Paroxysmal movements and constipation were reported in two patients, with one having a lipomyelomeningocele.", "CANTU SYNDROME": "Clinical features of Cantu syndrome include generalized congenital hypertrichosis, macrosomy at birth, narrow thorax, cardiomegaly, wide ribs, platyspondyly, hypoplastic ischiopubic branches, small obturator foramen, bilateral coxa valga, enlarged medullary canal, Erlenmeyer-flask-like long bones, generalized osteopenia, and a coarse facial appearance. Other reported findings include pericardial effusion, pulmonary hypertension, deep plantar creases, pyloric stenosis, elevated alkaline phosphatase levels, calcification of the arteriae thalamostriatae, and developmental delay. Facial changes evolve over time, with lengthening of the face, high nasal bridge, and prominent supraorbital ridges. Some patients may experience recurrent infections, low immunoglobulin levels, gastric bleeding, and cardiac manifestations such as patent ductus arteriosus, septal hypertrophy, and pulmonary hypertension. Learning difficulties tend to be mild, and a behavior phenotype involving anxiety and obsessive traits may emerge in the long term.", "TOLCHIN-LE CAIGNEC SYNDROME": "Patients with this rare genetic disorder exhibit a range of clinical features. Most commonly, they experience global developmental delay and mild to moderate intellectual impairment. Behavioral problems, including ADHD and autism, are also prevalent. Sleep disturbances, emotional lability, anxiety, restlessness, oppositional disorder, and aggressive episodes may occur. Some patients have craniosynostosis and dysmorphic features such as a prominent occiput, high forehead, micrognathia, hypertelorism, and broad nasal bridge. Other features include multiple osteochondromas, congenital anomalies like diastasis recti and umbilical hernia, and cardiac rhabdomyoma. Additional variable features include sensorineural deafness, hypermetropia, palatal abnormalities, flat feet, and arachnodactyly. Growth is generally normal, but some patients may have a large head circumference.", "HYPERPHOSPHATASIA WITH MENTAL RETARDATION SYNDROME 2, Hyperphosphatasia with mental retardation syndrome": "Clinical features of the rare genetic disorder include severe mental retardation, seizures, various neurologic abnormalities, greatly elevated alkaline phosphatase, delayed motor and speech development, hypotonia, delayed myelinization in the brain, distinct facial features (hypertelorism, downturned corners of the mouth), hypoplastic terminal phalanges and nails, anal anomalies, clefting of the hard and soft palates, hearing impairment, macrocephaly, cleft lip/palate, Hirschsprung disease, and persistent elevation of alkaline phosphatase activity. The disorder is characterized by hyperphosphatasia, severe psychomotor retardation, brachytelephalangy, and facial dysmorphism. Intracellular inclusions may be present in some tissues.", "ALAGILLE SYNDROME 1": "Clinical features of this rare genetic disorder include neonatal jaundice, posterior embryotoxon and retinal pigmentary changes in the eye, pulmonic valvular stenosis and peripheral arterial stenosis in the heart, abnormal vertebrae and decreased interpediculate distance in the bones, absent deep tendon reflexes and poor school performance in the nervous system, broad forehead, pointed mandible, and bulbous tip of the nose in the facies, and varying degrees of foreshortening in the fingers. Histology of the liver shows few intrahepatic bile ducts. Other features may include renal dysplasia, ocular abnormalities, and cardiovascular involvement such as moyamoya syndrome and vascular anomalies.", "NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA, MICROCEPHALY, AND SEIZURES": "Rare genetic disorder: \n- Neurodevelopmental disorder \n- Failure to thrive, developmental delay, axial hypotonia \n- Early-onset intractable seizures, status epilepticus \n- Global developmental delay, severe to profoundly impaired intellectual development \n- Poor or absent eye contact, cortical visual blindness, absent language \n- Peripheral spasticity, feeding difficulties, poor overall growth \n- Microcephaly, dysmorphic features \n- Brain anomalies: thin corpus callosum, brain atrophy, delayed myelination \n\nDevelopmental delay and encephalopathy: \n- Infantile spasms, myoclonic jerks, generalized seizures \n- Microcephaly, strabismus, axial hypotonia, appendicular spasticity, contractures \n- Cerebral atrophy, corpus callosum hypoplasia, ventricular enlargement \n\nSevere developmental delay and seizures: \n- Microcephaly, axial hypotonia, progressive spastic tetraplegia, hyperreflexia \n- Cerebral atrophy, corpus callosum hypoplasia, abnormal signal in the lentiform nucleus, cortical and subcortical atrophy", "SANDESTIG-STEFANOVA SYNDROME": "Clinical features of this rare genetic disorder include pre- and postnatal microcephaly, congenital cataract, ventricular septal defect, camptodactyly, clinodactyly, and rocker-bottom feet. Other common characteristics are a distinct facial gestalt with arched eyebrows, broad nasal bridge, low-set ears, and hypoplastic tragus. Patients also exhibit lethargy, hypotonia, and respiratory failure, often leading to early childhood death. Brain imaging shows abnormalities such as enlarged ventricles, thin corpus callosum, and delayed myelination. Additional findings include digital anomalies, congenital heart anomalies, and vision impairment. Autopsy findings include brain gliosis, lung hyperinflation, and streak ovaries.", "NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA, NEONATAL RESPIRATORY INSUFFICIENCY, AND THERMODYSREGULATION": "Children with this rare genetic disorder exhibit severe hypotonia, poor feeding, and overall growth, as well as neonatal respiratory insufficiency. They have profound global developmental delays, with no acquisition of milestones such as sitting, walking, or speaking. Eye contact is poor or absent, and cortical visual impairment is observed. Some patients develop glaucoma or cataracts, while others experience infantile seizures and unexplained fevers. Brain imaging shows thin or dysplastic corpus callosum, along with other nonspecific changes. Mild to moderate dysmorphic features may include a large forehead, upslanting palpebral fissures, and a short nose with flattened nasal bridge. Family history may include miscarriages.", "HOLOPROSENCEPHALY 12 WITH OR WITHOUT PANCREATIC AGENESIS": "Patients with this rare genetic disorder exhibit variable features suggestive of holoprosencephaly, including congenital pancreatic agenesis, type 1 diabetes mellitus, and pancreatic exocrine deficiency. Other common characteristics include intrauterine growth retardation, absence of the gallbladder, dysmorphic facial features, and brain abnormalities such as lobar holoprosencephaly and agenesis/hypoplasia of the corpus callosum. Some patients may also experience muscle weakness, seizures, learning difficulties, and developmental delays.", "NABAIS SA-DE VRIES SYNDROME, TYPE 1": "Patients: 2 unrelated patients (ages 4, 5, and 10)\nClinical features: Global developmental delay, delayed walking and speech, impaired intellectual development, variable behavioral abnormalities, hearing loss, congenital microcephaly, dysmorphic facial features (small forehead, round face, low anterior hairline, prominent glabella, highly arched eyebrows, synophrys, blepharophimosis, downslanted or narrow palpebral fissures, epicanthus, depressed or broad nasal bridge with short nose, bulbous nasal tip, anteverted nares, flat philtrum, micrognathia, pointed chin), simplified gyral pattern (patient 1), severely impaired intellectual development, bilateral optic nerve hypoplasia, vesicoureteral reflux, respiratory and gastrointestinal problems necessitating tracheostomy and feeding tube (patient 2).\n", "NABAIS SA-DE VRIES SYNDROME, TYPE 2": "Neurodevelopmental disorder with global developmental delay, speech delay, and intellectual impairment (IQ 45-53). Neonatal difficulties, including hypotonia, swallowing/breathing difficulties, failure to thrive, and bradycardia. Dysmorphic facial features (macrocephaly, high forehead, low-set ears, hypertelorism, etc.). Congenital heart disease (septal defects, stenosis, etc.) in 4 patients. Endocrine abnormalities (hypogonadism, hypothyroidism) in 3 patients. Other features include seizures, brain abnormalities, and ocular/reflux/sleep issues.", "DEVELOPMENTAL DELAY, IMPAIRED GROWTH, DYSMORPHIC FACIES, AND AXONAL NEUROPATHY": "Patients with a rare genetic disorder caused by mutations in the MORC2 gene exhibit a complex neurologic phenotype. Common features include hypotonia, muscle weakness, developmental delay, muscle atrophy, sensory impairment, areflexia, claw hands, scoliosis, and axonal degeneration. Additional characteristics include gait disturbances, intellectual impairment, brain abnormalities, short stature, microcephaly, dysmorphic facial features, hearing loss, retinopathy, and various other abnormalities. Phenotypic heterogeneity is observed, expanding the clinical spectrum associated with MORC2 mutations.", "PONTOCEREBELLAR HYPOPLASIA, TYPE 10": "Rare genetic disorder: developmental delay, severe intellectual disabilities, microcephaly, refractory seizures, poor overall growth, limb spasticity, hypertonia, hyperreflexia, axonal sensorimotor neuropathy, cortical dysgenesis, simplified gyral pattern, cerebellar vermian loss, thinning of brainstem, dysmorphic facial features (high-arched eyebrows, prominent eyes, esotropia, long palpebral fissures, broad nasal root, hypoplastic nasal alae), involvement of central and peripheral nervous systems, encephalopathy, failure to develop motor skills, delayed speech, progressive spasticity, pontocerebellar hypoplasia, thinning of corpus callosum, enlarged ventricles, white matter abnormalities, progressive spinal motor neuron loss, PCH10 designation, constipation, visual impairment, low hanging columella, tapered fingers, upper and lower limb hypertrichosis, kyphoscoliosis, hip abnormalities, cutaneous capillary vascular malformations, EEG abnormalities, global white matter volume reduction, thin corpus callosum, prominent cysterna magna, mild pontine hypoplasia.", "DEAFNESS, DYSTONIA, AND CEREBRAL HYPOMYELINATION": "Severe X-linked mental retardation with limited motor and cognitive development, dysmorphic features (microcephaly, strabismus), failure to thrive, deafness, early-onset dystonia, pyramidal signs (quadriplegia), seizures, optic atrophy. Brain MRI showed hypomyelination, cerebral/cerebellar atrophy. Transiently increased liver enzymes during febrile illness, but no abnormalities on liver ultrasound.", "DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 76": "Neurodevelopmental disorder with severely impaired intellectual development, microcephaly, seizures, and autistic behaviors. Hyperekplexia, global developmental delay, agenesis of the corpus callosum, ventricular dilatation, simplified gyral pattern, and colpocephaly. Refractory seizures, slowed background activity, slow spike-wave complexes, poor growth, microcephaly, spastic tetraplegia, kyphoscoliosis, and feeding difficulties. Severe global developmental delay, absent speech, seizures, hypotonia, spasticity, and feeding difficulties. Dysmorphic features including frontal bossing, bulbous nose, deep-set eyes, and strabismus.", "INTELLECTUAL DEVELOPMENTAL DISORDER WITH SEVERE SPEECH AND AMBULATION DEFECTS": "Rare genetic disorder: Global developmental delay, severely impaired intellectual development, absent language, hypotonia, features of autism (stereotypies), inability to walk independently (wide-based gait), dysmorphic features (prominent forehead, wide mouth, diastema, bulbous nose, hypertelorism, short phalanges/nails), small head circumference (not microcephaly), thin corpus callosum, generalized atrophy, mild periventricular gliosis (brain imaging), infantile spasms and generalized tonic-clonic seizures (1 patient).", "MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 2": "Text 1: Lethal multiple congenital anomaly disorder with Pierre-Robin sequence, dysmorphic facial features, joint contractures, and brain malformations. \n\nText 2: Profound developmental retardation, infantile seizures, hypsarrhythmia on EEG, and cortical and cerebellar atrophy. \n\nText 3: Early-onset epileptic encephalopathy with dysmorphic facial features, cortical atrophy, delayed myelination, and joint contractures. \n\nText 4: Lethal multiple congenital anomaly syndrome with hypotonia, seizures, dysmorphic facial features, and somatic overgrowth. \n\nText 5: Multiple congenital anomalies including macrocephaly, craniofacial anomalies, skeletal defects, and hypotonia. \n\nText 6: Early-onset epileptic encephalopathy with dysmorphic facial features, intellectual disability, severe motor disturbances, and decreased expression of CD16. \n\nText 7: Severe form of Simpson-Golabi-Behmel syndrome with multiple congenital anomalies, hypotonia, and neurologic impairment. \n\nText 8: Lethal multiple congenital anomaly syndrome with delayed psychomotor development, refractory seizures, dysmorphic facial features, and progressive cerebral atrophy.", "SCAF4": "Autistic features, hyperactivity, aggressive behavior, seizures (including myoclonic and intractable seizures), nonspecific white matter abnormalities, multicystic kidneys, unilateral kidney agenesis, cryptorchidism, ventricular septal defects, kyphosis/scoliosis, ankle rotation, brachydactyly, nonspecific dysmorphic facial features (including epicanthal folds and flat nasal bridge), global developmental delay (including mildly delayed walking), and mild intellectual disability with speech delay.", "MICROCEPHALY WITH OR WITHOUT CHORIORETINOPATHY, LYMPHEDEMA, OR MENTAL RETARDATION": "Clinical features of the rare genetic disorder include microcephaly, chorioretinopathy, mental retardation, lacunar depigmentation of the retina, microphthalmos, retinal folds, lymphedema, intellectual normality, congenital hypotonia, thick volar tissues, white lines on palm prints, coarse hair follicles, upslanting palpebral fissures, broad nose with rounded tip, long philtrum with thin upper lip, prominent large ears, reduced head circumference, and various ocular abnormalities.", "STRUCTURAL BRAIN ANOMALIES WITH IMPAIRED INTELLECTUAL DEVELOPMENT AND CRANIOSYNOSTOSIS": "Rare genetic disorder: Bicoronal synostosis, brain abnormalities, impaired intellectual development, learning disability, abnormal ventricles and corpus callosum, occult spina bifida, language delay, motor skills affected, progressive scoliosis, autism spectrum disorder, attention deficit-hyperactivity disorder, microcephaly, agenesis of corpus callosum, brachycephaly, cerebellar hypoplasia, scoliosis, tethered cord, facial anomalies, hypotonia, reduced reflexes, positive Babinski sign, feeding difficulties, hypertonia, neurogenic bladder dysfunction, speech difficulties, abnormal brain growth, premature cranial sutural synostosis, microcephaly, sagittal and bilambdoid sutures closure, ventriculomegaly, possible abnormalities in corpus callosum, posterior fossa, frontal and perisylvian cortex.", "UBR7": "Patients with this rare genetic disorder exhibit global developmental delay, impaired intellectual development, hypotonia, and absent speech. They may also have brisk reflexes, seizures, cardiac abnormalities, hypothyroidism, and genital anomalies. Other features include short stature, microcephaly, dysmorphic facial features, and various skeletal and gastrointestinal abnormalities. Brain imaging reveals ventricular enlargement, cortical atrophy, thin corpus callosum, delayed myelination, and white matter abnormalities.", "RBL2": "Text 1: Severe neurodevelopmental disorder with hypotonia, delayed crawling, no independent ambulation, severe developmental delay, impaired intellectual development, no social interaction, absent speech, stereotypic and autoaggressive behavior, nystagmus, strabismus (older sister), optic atrophy (younger brother), developmental regression, refractory myoclonic seizures, minor dysmorphic features, supra- and infratentorial atrophy, hyperostosis of the skull, thin corpus callosum, no microcephaly.\n\nText 2: Severe neurodevelopmental disorder with hypotonia, global developmental delay, unsteady walking, lower limb spasticity (2 patients), wheelchair-bound (2 patients), profound intellectual disability, limited or absent speech, well-controlled seizures (2 patients), ocular abnormalities (strabismus, hypermetropia, corneal clouding, myopia, anisometropia, astigmatism), normal hearing, progressive microcephaly (2 patients), sleep disturbances, irritability.", "PPP2CA": "Neurodevelopmental disorder with global developmental delay, impaired intellectual development, hypotonia, behavioral abnormalities (often autism spectrum disorder), seizures, microcephaly or macrocephaly, dysmorphic features (plagiocephaly, broad forehead, hypertelorism, etc.), visual problems (megalocornea), feeding problems, hernia, cardiac defects, single palmar crease, joint hypermobility. Nonspecific brain imaging findings (dilated ventricles, delayed myelination, absence/dysplasia of corpus callosum).", "Noonan syndrome-like disorder with loose anagen hair": "Clinical features of the rare genetic disorder include:\n- Short stature\n- Facial phenotype with macrocephaly, high forehead, hypertelorism, palpebral ptosis, and low-set and posteriorly rotated ears\n- Short neck with redundant skin\n- Enlarged cerebrospinal fluid spaces\n- Severe growth hormone deficiency\n- Mild psychomotor delay with attention deficit/hyperactivity disorder\n- Mild dilatation of the pulmonary root\n- Ectodermal abnormalities with darkly pigmented and hairless skin\n- Loose anagen hair syndrome with easily pluckable, sparse, thin, slow-growing, and silver-blond hair\n- Distinctive hyperactive behavior and cognitive deficits\n- Cardiac anomalies, including mitral valve and septal defects\n- Darkly pigmented skin with eczema or ichthyosis\n- Hypernasal voice\n- Skin hyperpigmentation, sparse light-colored hair, increased fine wrinkles, and ligamentous laxity\n- Developmental delay, hypotonia, and macrocephaly\n- Structural cardiac anomalies, polyhydramnios, high birth weight, and feeding tube requirement\n- Distinctive brain abnormalities, including relative megalencephaly and enlarged subarachnoid spaces\n- Cerebellar tonsillar ectopia\n- Prenatal diagnosis of cystic hygroma, hypertrophic cardiomyopathy, and absence of ductus venosus\n- Skeletal anomalies, including pectus carinatum and pectus excavatum\n- Clinical variability with features overlapping Noonan and CFC syndromes\n- Mutation in the SHOC2 gene\n- Optic nerve hypoplasia, nystagmus, poor hair growth, speech delay, and hyperactive behavior\n- Average stature, intellectual disability, high-arched palate, and clubbed nails in affected individuals.", "Progeria": "Clinical features of the rare genetic disorder, progeria, include a progeroid appearance, disproportionately large head, \"pinched\" facial features, lipodystrophy, stiffness of joints, senile appearance, arteriosclerosis, absence of subcutaneous fat, premature aging, cardiovascular complications, growth impairment, insulin resistance, dilated cardiomyopathy, hypergonadotropic hypogonadism, short stature, loss of subcutaneous fat, hair loss, tooth loss, low bone density, beaked nose, hyperlipidemia, atherosclerosis, and various malignancies.", "CHANARIN-DORFMAN SYNDROME": "Clinical features of the rare genetic disorder include congenital ichthyosis, hepatosplenomegaly, vacuolated granulocytes (Jordans anomaly), and myopathy. Pathological studies showed nonlysosomal triglyceride storage, and fibroblasts exhibited abnormal fatty acid metabolism. Other symptoms include failure to produce ketone bodies, fatty degeneration of the liver, cataracts, nystagmus, hearing loss, ataxia, and increased cerebrospinal fluid protein. The disorder can be recognized by lipid vacuoles in granulocytes, monocytes, and eosinophils. It is associated with psychomotor delay, neurologic deficits, and mild primary myopathy. Cerebral involvement has also been observed.", "WEAVER SYNDROME": "Clinical features of Weaver syndrome include accelerated growth and osseous maturation, unusual craniofacial appearance, hoarse and low-pitched cry, hypertonia with camptodactyly, psychomotor delay, looseness of skin, hernias, and dysmorphic facial features such as large bifrontal diameter, flat occiput, large ears, ocular hypertelorism, long philtrum, and relative micrognathia. Other characteristics may include accelerated harmonic skeletal maturation, platyspondyly, vertebral wedging, dental dysplasia, joint laxity, and thoracolumbar kyphosis. Weaver syndrome may be difficult to differentiate from Sotos syndrome, but early photographs may help distinguish between the two. Autosomal dominant inheritance has been suggested in some cases, while others occur sporadically. Some individuals with Weaver syndrome may also develop neoplasia, such as ovarian endodermal sinus tumor or acute lymphoblastic leukemia.", "Joubert syndrome": "Clinical features of the rare genetic disorder, Joubert syndrome, include agenesis of the vermis of the cerebellum, tremor, hypotonia, Dandy-Walker malformation, hypoplasia of the corpus callosum, occipital meningoencephalocele, coloboma of the optic nerve, cardiac malformations, cutaneous dimples, telecanthus, micrognathia, chorioretinal coloboma, large head, prominent forehead, high rounded eyebrows, epicanthal folds, ptosis, upturned nose, open mouth, low-set and tilted ears, oculomotor apraxia, hyperpnea, malformation of brainstem structures, temperament problems, hyperactivity, aggressiveness, dependency, severe cognitive and developmental impairment, malformation of cerebellar hemispheres, absence of decussation of superior cerebellar peduncles, dysmorphic facial features, and genetic heterogeneity.", "JOUBERT SYNDROME 14, Joubert syndrome": "Clinical features of Joubert syndrome include severe developmental delay, hypotonia, ataxia, abnormal breathing pattern, nystagmus, strabismus, and the molar tooth sign. Characteristic facial features include tall forehead, malar flattening, hypertelorism, deep-set eyes, downslanting palpebral fissures, ptosis, epicanthal folds, arched eyebrows, high nasal bridge, short philtrum with tented upper lip, open mouth, and posteriorly rotated low-set ears. Other variable features include retinal colobomas, postaxial polydactyly, cystic kidneys, occipital encephalocele, and posterior fossa abnormalities. Increased mortality is observed.", "JOUBERT SYNDROME 35, Joubert syndrome": "Clinical features of Joubert syndrome include agenesis of the vermis of the cerebellum, tremor, hypotonia, Dandy-Walker malformation, hypoplasia of the corpus callosum, occipital meningoencephalocele, coloboma of the optic nerve, cardiac malformations, cutaneous dimples, telecanthus, micrognathia, chorioretinal coloboma, large head, prominent forehead, high rounded eyebrows, epicanthal folds, ptosis, upturned nose, open mouth, low-set and tilted ears, oculomotor apraxia, hyperpnea, malformation of brainstem structures, temperament problems, cognitive impairment, physical developmental delays, molar tooth sign on neuroimaging, retinal dystrophy, renal cysts, dysmorphic facial features, developmental delay, ataxia, retinal rod-cone dystrophy, oculomotor apraxia, renal involvement, and dysmorphic facial features.", "JOUBERT SYNDROME 24, Joubert syndrome": "Joubert syndrome is a rare genetic disorder characterized by cerebellar vermis aplasia, the molar tooth sign on brain imaging, hypotonia, and delayed psychomotor development. Other features may include nystagmus, talipes equinovarus, spasticity, and renal abnormalities. Additional findings include postaxial hexadactyly, polymicrogyria, pachygyria, myelination defects, and various facial dysmorphic features. Cognitive and behavioral impairments are common, and brainstem malformations contribute to episodic hyperpnea and oculomotor apraxia. The disorder shows phenotypic variability and is associated with mutations in the TCTN2 gene.", "JOUBERT SYNDROME 18, Joubert syndrome": "Clinical features of the rare genetic disorder, Joubert syndrome, include vermis agenesis, molar tooth sign, kyphoscoliosis, polydactyly, camptodactyly, abnormal eye movements, breathing anomalies, severe mental retardation, joint laxity, intrauterine growth retardation, oral anomalies, micrognathia, horseshoe kidney, ventricular septal defect, tremor, hypotonia, episodic tachypnea, complex cardiac malformation, cutaneous dimples, telecanthus, chorioretinal coloboma, large head, prominent forehead, high rounded eyebrows, epicanthal folds, ptosis, upturned nose, open mouth, low-set and tilted ears, oculomotor apraxia, hyperpnea, malformation of brainstem structures, temperament problems, hyperactivity, aggressiveness, dependency, severe impairment in developmental attainments, malformation of multiple brainstem structures, phenotypic discordance, hypotonia evolving into ataxia, marked oculomotor apraxia, mental retardation, absence of decussation of superior cerebellar peduncles, dysmorphic facial features (long face, frontal prominence, bitemporal narrowing, ptosis, prominent nasal bridge and tip, prognathism, eyebrow abnormalities, trapezoid-shaped mouth, lower lip eversion, thick ear lobes), and extreme variability.", "RENPENNING SYNDROME 1": "Clinical features of the rare genetic disorder include X-linked mental retardation, short stature, moderate microcephaly, unremarkable facies, spastic diplegia, microphthalmia, choroid coloboma, camptodactyly, arachnodactyly, seizures, hypoplastic and malpositioned kidney, long narrow face, large anteverted ears, bulbous nose, maxillary hypoplasia, prognathism, low-set protruding ears, rounded face, micrognathia, long philtrum, prominent metopic suture, brachycephaly, small testes, intrauterine growth retardation, severe congenital heart defects, cleft or highly arched palate, abnormal ears, broad nasal bridge, malar hypoplasia, small mouth, hyperreflexia or spastic diplegia, triangular face, open mandibular angle, anal atresia, complete situs inversus, lean body habitus, iris coloboma, decreased head circumference, atrial septal defect, language delay, autistic features, anxiety, long triangular face, large ridged nose, half-depilated eyebrows, dysplastic or protruding ears, rough slightly sparse hair, progressive muscular atrophy, metacarpophalangeal ankylosis of the thumb, and velar dysfunction.", "STANKIEWICZ-ISIDOR SYNDROME": "Neurodevelopmental disorder with developmental delay, intellectual disability, autism, motor and speech delay. Variable features include hypotonia, deafness, feeding difficulties, thumb agenesis/hypoplasia. Cardiac, renal, and genital anomalies observed. Dysmorphic craniofacial features, low-set ears, retrognathia, hypertelorism, large nose. Eye abnormalities, pineal cyst on brain imaging.", "Bardet-Biedl syndrome": "Clinical features of Bardet-Biedl syndrome include renal abnormalities, retinal dystrophy, polydactyly, mental retardation, mild obesity, hepatic fibrosis, nephronophthisis, hypertension, calyceal clubbing, calyceal cysts, lobulated renal outlines, small testes and genitalia in men, menstrual irregularities and low estrogen levels in women, diabetes mellitus, vaginal atresia, hydrometrocolpos, hypogonadotropic hypogonadism, situs inversus, Hirschsprung disease, decreased corneal positive potential, anosmia, peripheral sensation decrease, cone-rod dysfunction, macular dystrophy, and taller affected offspring in BBS1 category.", "PACS2": "DEE66 is a rare genetic disorder characterized by early-onset seizures, including focal motor, autonomic, tonic, and generalized tonic-clonic seizures. Patients may also experience myoclonic seizures. Developmental delay, intellectual disability, delayed speech, and behavioral disturbances are common. Neurologic features include hypotonia, hand stereotypies, wide-based gait, hyperreflexia, nystagmus, myopia, and cortical visual impairment. Dysmorphic facial features may include coarse features, synophrys, hypertelorism, downslanting palpebral fissures, broad nasal root, thin upper lip, and wide mouth with downturned corners. Other features may include distal limb anomalies, cardiac septal defects, cryptorchidism, and hematologic disturbances. Brain MRI may show dysgenesis of the cerebellar folia, inferior vermian hypoplasia, mega cisterna magna, and hypothalamic fusion in some cases.", "KMT2A": "Clinical features of the rare genetic disorder include pre- and postnatal growth deficiency, psychomotor delay, round and flat face, short nose, hypertelorism, long philtrum, short palpebral fissures, low-set ears, high-arched palate, alternating convergent squint, dilatation of renal calyces, short and thick limbs, hairy elbows, short stature, rhizomelic shortening of limbs, heavy jaw, downslanting palpebral fissures, mild hypertelorism, thick alae, facial asymmetry, developmental delay, delayed speech, hypertrichosis of distal-lateral arms and proximal-lateral forearms, hypotonia, left-sided hypoplasia, left ptosis, epicanthal folds, dolichocephaly, telecanthus, synophrys, narrow and downslanting palpebral fissures, low nasal bridge, thin upper lip, sacral dimple, fifth finger clinodactyly, mild mental retardation, dolichocephaly, prominent forehead, low-set ears, triangular nostrils, short philtrum, high-arched palate, pectus excavatum, delayed bone age, mental retardation, hyperactivity, long eyelashes, thick or arched eyebrows, vertically narrow palpebral fissures, excessive hair on back, below 10th centile for height, sacral dimple, hypertelorism, broad nose, synophrys, small mouth, short fingers and/or toes, hypotonia, failure to thrive, seizures, pericentric inversion of chromosome 9, interstitial duplication of chromosome 12q14.1, thick eyebrows, long eyelashes, generalized hirsutism, hypertrichosis of elbows and back, postnatal growth retardation, intellectual disability, broad nasal bridge, clinodactyly, fleshy hands, hypotonia, normal bone age, and phenotypic overlap with Kabuki syndrome.", "ALPK3": "Clinical features of the rare genetic disorder include pediatric cardiomyopathy, severe left ventricular dilation, reduced contractility of both ventricles, mitral and tricuspid regurgitation, cardiomegaly, subendocardial fibroelastosis, absence of desmosomal proteins, hydrops fetalis, cardiac hypertrophy, biventricular dilation, repolarization abnormalities, concentric left ventricular hypertrophy, prolonged QT interval, inferolateral ST depression, biatrial enlargement, large ventricular voltages, multiple pterygia, skeletal muscle underdevelopment, and mild facial dysmorphism.", "PQBP1": "Clinical features of the rare genetic disorder include X-linked mental retardation, short stature, moderate microcephaly, unremarkable facies, spastic diplegia, microphthalmia, choroid coloboma, camptodactyly, arachnodactyly, seizures, hypoplastic and malpositioned kidney, long narrow face, large anteverted ears, bulbous nose, maxillary hypoplasia, prognathism, low-set protruding ears, rounded face, micrognathia, long philtrum, prominent metopic suture, brachycephaly, small testes, intrauterine growth retardation, severe congenital heart defects, cleft or highly arched palate, abnormal ears, broad nasal bridge, malar hypoplasia, small mouth, hyperreflexia or spastic diplegia, triangular face, open mandibular angle, anal atresia, complete situs inversus, lean body habitus, iris coloboma, decreased head circumference, atrial septal defect, language delay, autistic features, anxiety, long triangular face, large ridged nose, half-depilated eyebrows, dysplastic or protruding ears, rough slightly sparse hair, progressive muscular atrophy, metacarpophalangeal ankylosis of the thumb, and velar dysfunction.", "ROTHMUND-THOMSON SYNDROME, TYPE 2, Rothmund-Thomson syndrome": "Clinical features of the rare genetic disorder, Rothmund-Thomson syndrome (RTS), include poikiloderma, lenticular opacities, atrophy, pigmentation, telangiectasia, juvenile cataract, saddle nose, congenital bone defects, disturbances of hair growth, hypogonadism, severe skeletal dysplasia, joint abnormalities, kyphoscoliosis, hypermobility, cutaneous ulcers, mesodermal dysgenesis of the iris, hypodontia, soft tissue contractures, proportionate short stature, anemia, and osteogenic sarcoma. There are two forms of RTS: type 1, characterized by poikiloderma without osteosarcoma, and type 2, characterized by poikiloderma with an increased risk of osteosarcoma and deleterious mutations in the RECQL4 gene. Clinical variability exists, with some patients exhibiting additional features such as bilateral radial aplasia, cleft palate, micrognathia, anal atresia, patellar aplasia/hypoplasia, and sensorineural deafness.", "PGAP3": "Clinical features of HPMRS4 include severely delayed psychomotor development, hypotonia, inability to speak or walk independently, seizures, dysmorphic facial features (hypertelorism, upslanting palpebral fissures, broad nasal bridge, short nose, long philtrum, tented upper lip, full cheeks, large fleshy earlobes), postnatal microcephaly, cleft palate, thin corpus callosum, dilated lateral ventricles, increased serum alkaline phosphatase, bulbous nose, epicanthal folds, megalocornea, overlapping toes, abnormal dentition, hypoplastic cerebellum, communication between third ventricle and posterior fossa, brain atrophy, hearing loss, characteristic facies, abnormal teeth, megalocornea, congenital heart defects, impaired intellectual development, hypotonia, epilepsy, abnormal MRI findings, microretrognathia, wide anterior fontanel, left ear pit, pectus carinatum, hypoplastic nails, left inguinal hernia, patent foramen ovale, frontoparietal atrophy, bilateral enlargement of lateral ventricles, profound developmental delay, aspiration pneumonia, blue sclerae, hypertrophic gums, thin sparse hair, pectus excavatum, umbilical hernia, unilateral pes equinovarus, callosal dysgenesis, minor hippocampal structural anomaly, and elevated alkaline phosphatase levels.", "Rubinstein-Taybi syndrome": "Clinical features of Rubinstein-Taybi syndrome (RSTS) include mental retardation, broad thumbs and toes, facial abnormalities, juvenile glaucoma, talon cusps, pheochromocytoma, broad halluces, persistent fetal pads, shawl scrotum, frequent fractures, constipation, collapsible laryngeal walls, short upper lip, pouting lower lip, high slit-like palate, phenotypic overlap with Saethre-Chotzen syndrome, agenesis of the corpus callosum, iris coloboma, megacolon, pulmonary hypertension, mitral valve regurgitation, patent ductus arteriosus, cardiac abnormalities, increased risk of tumor formation, slipped capital femoral epiphysis, patellar dislocation, premature thelarche, defective antibody response, orodental features, varicella meningoencephalitis, visual difficulties, keloids, eating problems, spinal curvature, joint laxity, behavioral problems, and growth abnormalities. Incomplete RSTS may present with broad thumbs, antimongoloid slant of the palpebral fissures, beaked nose, and characteristic facial appearance.", "BLEPHAROPHIMOSIS, PTOSIS, AND EPICANTHUS INVERSUS": "Clinical features of this rare genetic disorder, known as blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), include small palpebral fissures, epicanthus inversus, low nasal bridge, and ptosis of the eyelids. It is distinct from congenital ptosis. Female infertility is a common effect, with primary ovarian failure and small atrophic ovaries observed. BPES can be inherited as an autosomal dominant sex-limited trait. Some cases of BPES are associated with premature ovarian failure. Mental retardation or developmental delay may be present in individuals with other malformation syndromes.", "ALAGILLE SYNDROME 1, WOLFF-PARKINSON-WHITE SYNDROME, Alagille syndrome": "Clinical features of this rare genetic disorder include short PR interval, prolonged QRS, and a slurred-up stroke of the R wave called a delta wave. Patients are prone to paroxysmal supraventricular tachycardia. The disorder can be familial and has been associated with cardiomyopathy. Other features include posterior embryotoxon, retinal pigmentary changes, pulmonic valvular stenosis, peripheral arterial stenosis, abnormal vertebrae, poor school performance, broad forehead, pointed mandible, bulbous tip of the nose, and varying degrees of foreshortening in the fingers. Liver involvement is characterized by neonatal jaundice, hepatic artery and portal vein abnormalities, and few intrahepatic bile ducts. Craniofacial involvement includes a prominent forehead, pointed chin, and eye abnormalities. Skeletal involvement includes abnormalities in vertebral bodies and short distal phalanges. Ocular involvement includes posterior embryotoxon, iris abnormalities, and retinal changes. Kidney involvement includes renal dysplasia, renal artery stenosis, and hypertension. Cardiovascular involvement includes abdominal coarctation of the aorta, moyamoya syndrome, and noncardiac vascular anomalies. Other features include caudal dysplasia sequence, insensitivity to growth hormone, papillary thyroid carcinoma, xanthomas, and supernumerary digital flexion creases.", "MENTAL RETARDATION, AUTOSOMAL DOMINANT 53": "In Kury et al (2017), patients with a rare genetic disorder showed delayed psychomotor development, intellectual disability (ranging from mild to severe), hypotonia, delayed or absent speech, behavioral abnormalities (including autistic features), and some had seizures. Dysmorphic facial features were also observed in some patients. Brain imaging was mostly normal, but some patients had abnormalities such as a thickened corpus callosum or microcephaly. \n\nIn Akita et al (2018), patients with MRD53 had seizures starting in infancy, severely impaired neurologic development, poor overall growth, small head circumference, and profound intellectual disability. Some patients were nonverbal and had motor impairments. Brain imaging showed progressive cerebellar atrophy in one patient. These patients were identified through whole-exome sequencing in a cohort of individuals with neurodevelopmental disorders.", "MENTAL RETARDATION, AUTOSOMAL DOMINANT 54": "Kury et al (2017) described a rare genetic disorder characterized by delayed psychomotor development, intellectual disability (ranging from mild to severe), hypotonia, delayed walking and speech, behavioral abnormalities (including autistic features), poor overall growth, seizures, EEG abnormalities, visual anomalies, gastrointestinal difficulties, dysmorphic facial features, and other variable features such as ectodermal dysplasia, food allergies, and breathing anomalies. Akita et al (2018) reported two unrelated Japanese boys with the disorder, one presenting with mild intellectual disability, seizures, and hypotonia, and the other with severely delayed development, inability to speak or hold his head, abnormal eye movements, and progressive cerebellar atrophy.", "BOSMA ARHINIA MICROPHTHALMIA SYNDROME": "Clinical features of this rare genetic disorder, known as Bosma syndrome or arhinia, include congenital absence of the nose and anterior nasopharynx, hypoplasia of the eyes, sensory abnormalities of taste and smell, impaired vision with cataracts and colobomata, bilateral inguinal hernias, cryptorchidism, and hypogonadotropic hypogonadism. Other common characteristics include high-arched or cleft palate, absent paranasal sinuses, hypoplastic maxilla, choanal atresia, and ocular abnormalities such as anophthalmia or microphthalmia, uveal coloboma, and cataract. Most individuals with this disorder have normal intelligence.", "SCHEIE SYNDROME, Mucopolysaccharidoses": "Clinical features of Scheie syndrome, a rare genetic disorder, include stiff joints, clouding of the cornea, survival to a late age with little impairment of intellect, and aortic regurgitation. Diagnosis is often made in adulthood, with symptoms appearing after age 5. Other characteristics include facial abnormalities, cardiovascular issues, respiratory problems, musculoskeletal abnormalities, and developmental delay.", "Baraitser-Winter syndrome": "Clinical features of the rare genetic disorder include iris coloboma, bilateral ptosis, hypertelorism, broad nasal bridge, prominent epicanthal folds, short stature, mental retardation, craniofacial dysmorphism, edema, narrowing of the frontal part of the skull, arched eyebrows, trigonocephaly, hypertelorism with a broad root and bridge of the nose, large mouth with a fine upper lip and everted lower lip, prominent upper central incisors, posteriorly rotated hypoplastic ears, high-arched palate, short and broad neck, widely spaced hypoplastic inverted nipples, neonatal edema followed by significant weight loss, complex epilepsy, pachygyria, limited extension at knees and elbows, multiple craniofacial and skeletal dysmorphic features, multiple eyelid colobomas, structural anomaly of the corpus callosum, brachycephaly, wide forehead, widow's peak, macrostomia, prominent lips, midline alveolar cleft, small and grooved chin, ear anomalies, Dandy-Walker anomaly, gray matter heterotopia, brachyacrocephaly, absent nasal tip, wide columella, carp-like mouth, submucous cleft of the soft palate, urogenital sinus, periventricular nodular heterotopia, cystic areas in the white matter, short stature, microcephaly, intellectual disability, seizures, hearing loss, reduction of shoulder girdle muscle bulk, progressive joint stiffness, muscular involvement, congenital arthrogryposis, cleft lip and palate, hallux duplex, congenital heart defects, renal tract anomalies, sensorineural deafness, dysmorphic facial features, ridged metopic sutures, iris or retinal coloboma, pectus deformities, tracheoesophageal fistula, esophageal atresia, distal skeletal anomalies, hypertrichosis, excess skin, lytic lesions of the skull, atrial septal defect, mild joint contractures, wavy eyebrows, dense eyelashes, wide mouth, prominent chin, and hoarse voice.", "Silver-Russell syndrome": "Silver-Russell syndrome (SRS) is characterized by low birth weight, short stature, triangular face, broad forehead, small chin, thin mouth, body asymmetry, hepatocellular carcinoma, clinodactyly, growth deficiency, camptodactyly, genital abnormalities, feeding problems, sweating, pallor, special education needs, UPD of chromosome 7, gastrointestinal symptoms, ophthalmologic abnormalities, impaired glucose tolerance, hypertension, hypercholesterolemia, educational achievement, and absence of typical childhood characteristics in adulthood. Molecular confirmation is necessary for diagnosis in adults.", "CORNELIA DE LANGE SYNDROME 1, Cornelia de Lange syndrome": "Thin vermilion border Bilateral single transverse palmar creases Global developmental delay Intrauterine growth retardation Anteverted nares Hypoplastic labia majora Curly eyelashes Posteriorly rotated ears Thick eyebrow Micromelia Cutis marmorata Micrognathia Hypoplastic nipples Downturned corners of mouth Small hand Brachycephaly Clinodactyly of the 5th finger Oligodactyly Depressed nasal bridge Generalized hirsutism Proximal placement of thumb Short stature Downturned corners of mouth Feeding difficulties in infancy Truncal obesity Conductive hearing impairment Asymmetric growth Long philtrum Toe syndactyly Micromelia Global developmental delay Short nose Hearing impairment Cryptorchidism Thin vermilion border Myopia Low posterior hairline Abnormally low-pitched voice Micrognathia Abnormality of speech or vocalization Short stature Widely spaced teeth Radioulnar synostosis Wide nasal bridge Low-set ears Long eyelashes Limited elbow extension Wide nasal bridge Intestinal malrotation Severe postnatal growth retardation Intellectual disability, severe Proximal placement of thumb Short 1st metacarpal Attention deficit hyperactivity disorder Microcephaly Failure to thrive Hypoplasia of penis Toe syndactyly Gastroesophageal reflux Thick eyebrow Premature birth Abnormal aggressive, impulsive or violent behavior Highly arched eyebrow obsolete Abnormality of the ulna Prenatal movement abnormality Atrial septal defect Abnormality of cardiovascular system morphology Synophrys Synophrys Intellectual disability Short foot Microcephaly Talipes Intellectual disability, severe Ptosis Blepharitis High palate Low-set ears Strabismus Sensorineural hearing impairment Seizure Increased nuchal translucency Thickened helices", "CORNELIA DE LANGE SYNDROME 2, Cornelia de Lange syndrome": "Thin vermilion border Bilateral single transverse palmar creases Global developmental delay Intrauterine growth retardation Anteverted nares Hypoplastic labia majora Curly eyelashes Posteriorly rotated ears Thick eyebrow Micromelia Cutis marmorata Micrognathia Hypoplastic nipples Downturned corners of mouth Small hand Brachycephaly Clinodactyly of the 5th finger Oligodactyly Depressed nasal bridge Generalized hirsutism Proximal placement of thumb Short stature Downturned corners of mouth Feeding difficulties in infancy Truncal obesity Conductive hearing impairment Asymmetric growth Long philtrum Toe syndactyly Micromelia Global developmental delay Short nose Hearing impairment Cryptorchidism Thin vermilion border Myopia Low posterior hairline Abnormally low-pitched voice Micrognathia Abnormality of speech or vocalization Short stature Widely spaced teeth Radioulnar synostosis Wide nasal bridge Low-set ears Long eyelashes Limited elbow extension Wide nasal bridge Intestinal malrotation Severe postnatal growth retardation Intellectual disability, severe Proximal placement of thumb Short 1st metacarpal Attention deficit hyperactivity disorder Microcephaly Failure to thrive Hypoplasia of penis Toe syndactyly Gastroesophageal reflux Thick eyebrow Premature birth Abnormal aggressive, impulsive or violent behavior Highly arched eyebrow obsolete Abnormality of the ulna Prenatal movement abnormality Atrial septal defect Abnormality of cardiovascular system morphology Synophrys Synophrys Intellectual disability Short foot Microcephaly Talipes Intellectual disability, severe Ptosis Blepharitis High palate Low-set ears Strabismus Sensorineural hearing impairment Seizure Increased nuchal translucency Thickened helices", "Cornelia de Lange syndrome": "Thin vermilion border Bilateral single transverse palmar creases Global developmental delay Intrauterine growth retardation Anteverted nares Hypoplastic labia majora Curly eyelashes Posteriorly rotated ears Thick eyebrow Micromelia Cutis marmorata Micrognathia Hypoplastic nipples Downturned corners of mouth Small hand Brachycephaly Clinodactyly of the 5th finger Oligodactyly Depressed nasal bridge Generalized hirsutism Proximal placement of thumb Short stature Downturned corners of mouth Feeding difficulties in infancy Truncal obesity Conductive hearing impairment Asymmetric growth Long philtrum Toe syndactyly Micromelia Global developmental delay Short nose Hearing impairment Cryptorchidism Thin vermilion border Myopia Low posterior hairline Abnormally low-pitched voice Micrognathia Abnormality of speech or vocalization Short stature Widely spaced teeth Radioulnar synostosis Wide nasal bridge Low-set ears Long eyelashes Limited elbow extension Wide nasal bridge Intestinal malrotation Severe postnatal growth retardation Intellectual disability, severe Proximal placement of thumb Short 1st metacarpal Attention deficit hyperactivity disorder Microcephaly Failure to thrive Hypoplasia of penis Toe syndactyly Gastroesophageal reflux Thick eyebrow Premature birth Abnormal aggressive, impulsive or violent behavior Highly arched eyebrow obsolete Abnormality of the ulna Prenatal movement abnormality Atrial septal defect Abnormality of cardiovascular system morphology Synophrys Synophrys Intellectual disability Short foot Microcephaly Talipes Intellectual disability, severe Ptosis Blepharitis High palate Low-set ears Strabismus Sensorineural hearing impairment Seizure Increased nuchal translucency Thickened helices", "CORNELIA DE LANGE SYNDROME 5, Cornelia de Lange syndrome": "Thin vermilion border Bilateral single transverse palmar creases Global developmental delay Intrauterine growth retardation Anteverted nares Hypoplastic labia majora Curly eyelashes Posteriorly rotated ears Thick eyebrow Micromelia Cutis marmorata Micrognathia Hypoplastic nipples Downturned corners of mouth Small hand Brachycephaly Clinodactyly of the 5th finger Oligodactyly Depressed nasal bridge Generalized hirsutism Proximal placement of thumb Short stature Downturned corners of mouth Feeding difficulties in infancy Truncal obesity Conductive hearing impairment Asymmetric growth Long philtrum Toe syndactyly Micromelia Global developmental delay Short nose Hearing impairment Cryptorchidism Thin vermilion border Myopia Low posterior hairline Abnormally low-pitched voice Micrognathia Abnormality of speech or vocalization Short stature Widely spaced teeth Radioulnar synostosis Wide nasal bridge Low-set ears Long eyelashes Limited elbow extension Wide nasal bridge Intestinal malrotation Severe postnatal growth retardation Intellectual disability, severe Proximal placement of thumb Short 1st metacarpal Attention deficit hyperactivity disorder Microcephaly Failure to thrive Hypoplasia of penis Toe syndactyly Gastroesophageal reflux Thick eyebrow Premature birth Abnormal aggressive, impulsive or violent behavior Highly arched eyebrow obsolete Abnormality of the ulna Prenatal movement abnormality Atrial septal defect Abnormality of cardiovascular system morphology Synophrys Synophrys Intellectual disability Short foot Microcephaly Talipes Intellectual disability, severe Ptosis Blepharitis High palate Low-set ears Strabismus Sensorineural hearing impairment Seizure Increased nuchal translucency Thickened helices", "CORNELIA DE LANGE SYNDROME 3 WITH OR WITHOUT MIDLINE BRAIN DEFECTS, Cornelia de Lange syndrome": "Thin vermilion border Bilateral single transverse palmar creases Global developmental delay Intrauterine growth retardation Anteverted nares Hypoplastic labia majora Curly eyelashes Posteriorly rotated ears Thick eyebrow Micromelia Cutis marmorata Micrognathia Hypoplastic nipples Downturned corners of mouth Small hand Brachycephaly Clinodactyly of the 5th finger Oligodactyly Depressed nasal bridge Generalized hirsutism Proximal placement of thumb Short stature Downturned corners of mouth Feeding difficulties in infancy Truncal obesity Conductive hearing impairment Asymmetric growth Long philtrum Toe syndactyly Micromelia Global developmental delay Short nose Hearing impairment Cryptorchidism Thin vermilion border Myopia Low posterior hairline Abnormally low-pitched voice Micrognathia Abnormality of speech or vocalization Short stature Widely spaced teeth Radioulnar synostosis Wide nasal bridge Low-set ears Long eyelashes Limited elbow extension Wide nasal bridge Intestinal malrotation Severe postnatal growth retardation Intellectual disability, severe Proximal placement of thumb Short 1st metacarpal Attention deficit hyperactivity disorder Microcephaly Failure to thrive Hypoplasia of penis Toe syndactyly Gastroesophageal reflux Thick eyebrow Premature birth Abnormal aggressive, impulsive or violent behavior Highly arched eyebrow obsolete Abnormality of the ulna Prenatal movement abnormality Atrial septal defect Abnormality of cardiovascular system morphology Synophrys Synophrys Intellectual disability Short foot Microcephaly Talipes Intellectual disability, severe Ptosis Blepharitis High palate Low-set ears Strabismus Sensorineural hearing impairment Seizure Increased nuchal translucency Thickened helices", "INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC, CABEZAS TYPE": "Clinical features of the rare genetic disorder include:\n- Short stature\n- Patulous lips\n- Difficulty in speech\n- Short thumbs and little fingers with adduction\n- Hypotonia at a young age, later followed by hypertonia, restlessness, and seizures\n- Pes planus\n- Small testes and delayed sex development in males\n- Mild facial dysmorphisms, such as microcephaly, hypertelorism, micrognathia, and macrostomia\n- Brachydactyly\n- Macroglossia\n- Unique gait with toes pointing inwards\n- Muscle wasting in lower legs\n- Kyphosis\n- Joint hyperextensibility\n- Tremor\n- Impaired speech and decreased attention span\n- Mental retardation with IQ scores ranging from 29 to 57\n- Minor dysmorphic features in carrier females\n- Language and learning problems in carrier females\n- Coarse face\n- Downslanting palpebral fissures\n- Large bulbous nose\n- Hypoplastic earlobes\n- Moderate short stature\n- Central obesity\n- Unprovoked aggressive outbursts\n- Fine intention tremor\n- Pes cavus\n- Abnormalities of the toes\n- Intrauterine growth retardation in one twin\n- Scaphocephaly in the other twin\n- Intellectual disability with severe speech impairment\n- Behavioral problems, gait abnormalities, tremor, and seizures\n- Hypogonadism, short stature, small hands, kyphosis, gynecomastia, and macrocephaly\n- Dysmorphic facial features including high forehead, prominent lower lip, and malformed/abnormally positioned ears\n- Neuroimaging abnormalities, including ventriculomegaly, polymicrogyria, cortical dysplasia, white matter abnormalities, and cerebellar vermis atrophy.", "INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC, NASCIMENTO TYPE": "Clinical features of the rare genetic disorder include mental retardation, dysmorphic features such as synophrys, upslanted palpebral fissures, large mouth with downturned corners and thin lips, short and broad neck, low posterior hairline, and hair whorls. Other characteristics include midface hypoplasia, wide face, large head circumference, marked generalized hirsutism, myxedematous appearance, widely spaced nipples, small penis, small flat feet, dry skin, onychodystrophy, seizures, absent speech, white matter hypodensities, and increased risk of acute myeloid leukemia. The disorder is X-linked and affects males, with similar physical features including a large head, prominent supraorbital ridges, synophrys, deep-set almond-shaped eyes, large ears, wide mouth, widely spaced nipples, large great toes, hypopigmented skin spots, abnormal hair whorls, low posterior hairline, short neck, micropenis, poor speech, seizures, aggressive behavior, and echolalia.", "CORNELIA DE LANGE SYNDROME 4 WITH OR WITHOUT MIDLINE BRAIN DEFECTS, Cornelia de Lange syndrome": "Thin vermilion border Bilateral single transverse palmar creases Global developmental delay Intrauterine growth retardation Anteverted nares Hypoplastic labia majora Curly eyelashes Posteriorly rotated ears Thick eyebrow Micromelia Cutis marmorata Micrognathia Hypoplastic nipples Downturned corners of mouth Small hand Brachycephaly Clinodactyly of the 5th finger Oligodactyly Depressed nasal bridge Generalized hirsutism Proximal placement of thumb Short stature Downturned corners of mouth Feeding difficulties in infancy Truncal obesity Conductive hearing impairment Asymmetric growth Long philtrum Toe syndactyly Micromelia Global developmental delay Short nose Hearing impairment Cryptorchidism Thin vermilion border Myopia Low posterior hairline Abnormally low-pitched voice Micrognathia Abnormality of speech or vocalization Short stature Widely spaced teeth Radioulnar synostosis Wide nasal bridge Low-set ears Long eyelashes Limited elbow extension Wide nasal bridge Intestinal malrotation Severe postnatal growth retardation Intellectual disability, severe Proximal placement of thumb Short 1st metacarpal Attention deficit hyperactivity disorder Microcephaly Failure to thrive Hypoplasia of penis Toe syndactyly Gastroesophageal reflux Thick eyebrow Premature birth Abnormal aggressive, impulsive or violent behavior Highly arched eyebrow obsolete Abnormality of the ulna Prenatal movement abnormality Atrial septal defect Abnormality of cardiovascular system morphology Synophrys Synophrys Intellectual disability Short foot Microcephaly Talipes Intellectual disability, severe Ptosis Blepharitis High palate Low-set ears Strabismus Sensorineural hearing impairment Seizure Increased nuchal translucency Thickened helices", "TRICHOHEPATONEURODEVELOPMENTAL SYNDROME": "Rare genetic disorder: Dysmorphic facial features (coarse facies, ptosis, downturned mouth, simple ears), unusual hair (coarse, woolly, curly), microcephaly, brachycephaly, severe global developmental delay, liver dysfunction, pruritus, hypotonia, joint laxity or distal arthrogryposis, nipple hypoplasia, overlapping toes, midface hypoplasia, hypertelorism, dental abnormalities, plagiocephaly, narrow chest, hip dysplasia, bilateral clubfoot, severe developmental delay, nonverbal with generalized hypotonia, cerebral atrophy, abnormal ventricular morphology, immunodeficiency, recurrent infections.", "WDR37": "Patients with mutations in the WDR37 gene exhibit overlapping ocular and neurologic phenotypes. Common features include eye anomalies, dysmorphic facial features, seizures, feeding difficulties, developmental delay, intellectual disability, hypotonia, microcephaly, congenital cardiac defects, and hearing loss. Male patients may have micropenis and undescended testes, while female patients may experience delayed thelarche and menarche. Brain malformations include gyral hypoplasia, hippocampal dysplasia, reduced white matter volume, thin corpus callosum, brainstem and cerebellar hypoplasia, and enlarged posterior fossa. Other features such as spastic quadriplegia and neuroregression may be present in some patients. Additional multisystem phenotypes include craniofacial anomalies, hearing loss, genitourinary anomalies, feeding disorders, gastrointestinal anomalies, and skeletal anomalies. Severe neurologic impairment and cardiac anomalies can lead to early mortality.", "HNRNPK": "Clinical features of the rare genetic disorder, known as Okamoto syndrome or Au-Kline syndrome (AUKS), include congenital hydronephrosis, severe mental retardation, growth failure, generalized floppiness, and cleft palate. Facial characteristics consist of midface hypoplasia, hypertrichosis, long eyelashes, prominent eyes, epicanthus, low-set ears, long ear lobe, flat nasal bridge, short upturned nose, long philtrum, and webbed neck. Other common features include cardiac anomalies, developmental delay, hypotonia, and skeletal abnormalities. Additional findings may include anal stenosis, splenomegaly, brain abnormalities, and genitourinary anomalies. A mutation in the HNRNPK gene has been identified in some patients. AUKS shares similarities with Kabuki syndrome but has distinct features such as ridged metopic sutures, open mouths, and high pain tolerance.", "Alagille syndrome": "Clinical features of this rare genetic disorder include neonatal jaundice, posterior embryotoxon and retinal pigmentary changes in the eye, pulmonic valvular stenosis and peripheral arterial stenosis in the heart, abnormal vertebrae and decreased interpediculate distance in the bones, absent deep tendon reflexes and poor school performance in the nervous system, broad forehead, pointed mandible, and bulbous tip of the nose in the facies, and varying degrees of foreshortening in the fingers. Histology of the liver shows few intrahepatic bile ducts. Other features may include renal dysplasia, ocular abnormalities, and cardiovascular involvement such as moyamoya syndrome and vascular anomalies.", "KLEEFSTRA SYNDROME 1": "Clinical features of the rare genetic disorder include mental retardation, hypotonia, characteristic facial features (microcephaly, brachycephaly, hypertelorism, synophrys, midface hypoplasia, protruding tongue, eversion of the lower lip, prognathism), increased birth weight, childhood obesity, delayed motor function, congenital heart defects, seizures, micropenis, cryptorchidism, vesicoureteral reflux, tracheo-/bronchomalacia, gastroesophageal reflux, abnormal brain imaging, behavioral changes in adolescence (apathy, aggression, psychosis, autistic features, catatonia, bipolar mood disorder, regression in daily function and cognitive abilities), and white matter abnormalities on brain imaging. Haploinsufficiency for the EHMT1 gene is responsible for the main phenotypic features.", "Rothmund-Thomson syndrome": "Clinical features of the rare genetic disorder, Rothmund-Thomson syndrome (RTS), include poikiloderma, lenticular opacities, atrophy, pigmentation, telangiectasia, juvenile cataract, saddle nose, congenital bone defects, disturbances of hair growth, hypogonadism, severe skeletal dysplasia, joint abnormalities, kyphoscoliosis, hypermobility, cutaneous ulcers, mesodermal dysgenesis of the iris, hypodontia, soft tissue contractures, proportionate short stature, anemia, and osteogenic sarcoma. There are two forms of RTS: type 1, characterized by poikiloderma without osteosarcoma, and type 2, characterized by poikiloderma with an increased risk of osteosarcoma and deleterious mutations in the RECQL4 gene. Clinical variability exists, with some patients exhibiting additional features such as bilateral radial aplasia, inflammatory gut disorders, cleft palate, micrognathia, anal atresia, patellar aplasia/hypoplasia, and sensorineural deafness.", "BARTH SYNDROME": "Clinical features of the rare genetic disorder described in the texts include dilated cardiomyopathy, neutropenia, skeletal myopathy, abnormal mitochondria, endocardial fibroelastosis, short stature, abnormal carnitine metabolism, elevated urinary levels of certain organic acids, recurrent infections, delayed motor milestones, proximal muscle weakness, bacterial and fungal infections, failure to thrive, mild facial weakness, learning disabilities, increased excretion of 3-methylglutaconic acid, and variable neutrophil count. The disorder shows X-linked inheritance and has high mortality in the first few years of life, although some patients can reach adulthood with intrafamilial variability in symptoms.", "INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISTIC FEATURES AND LANGUAGE DELAY, WITH OR WITHOUT SEIZURES": "This study describes a neurodevelopmental disorder characterized by global developmental delay, impaired intellectual development, poor speech and language acquisition, and behavioral abnormalities such as autism. Some patients had seizures, chronic constipation, and dysmorphic features including large ears, thick eyebrows, and deep-set eyes. Brain imaging was normal. In some families, affected individuals had a parent with neuropsychiatric and/or behavioral abnormalities.", "ECTODERMAL DYSPLASIA WITH FACIAL DYSMORPHISM AND ACRAL, OCULAR, AND BRAIN ANOMALIES": "Patients with this rare genetic disorder exhibit linear hypopigmentation and hypotrichosis along the lines of Blaschko. They also have facial dysmorphism, including microstomia, malar hypoplasia, downslanting palpebral fissures, and a broad nasal bridge. Acral anomalies such as brachydactyly, syndactyly, and a broad first toe are present, along with dental anomalies like oligodontia, microdontia, conical teeth, and abnormal enamel. Ocular anomalies include microphthalmia, strabismus, and myopia. Brain MRI reveals diffuse cystic leukoencephalopathy with mildly enlarged lateral ventricles, but no intellectual or neurologic impairment is observed.", "CEBALID SYNDROME": "CEBALID syndrome is characterized by global developmental delay, hypotonia, feeding difficulties, intellectual impairment, and speech delay. Patients often have abnormal craniofacial development, including skull shape abnormalities, frontal bossing, midface hypoplasia, and ear anomalies. Brain imaging may show abnormalities such as rhombencephalosynapsis and perisylvian polymicrogyria. Some patients may have seizures, thin lips, dental crowding, and hernias. A milder form of the syndrome may present with milder dysmorphic facies, conductive hearing loss, and expressive language delay.", "TREACHER COLLINS SYNDROME 4": "Patients with Treacher Collins syndrome and mutations in the POLR1B gene exhibit downslanting palpebral fissures, malar hypoplasia, mandibular hypoplasia, microtia, atresia of the external ear canal, conductive deafness, facial asymmetry, cleft palate, and choanal atresia. In the neonatal period, they often require tube feedings and may undergo intubation or tracheostomy.", "NEUROOCULOCARDIOGENITOURINARY SYNDROME": "Patients with mutations in the WDR37 gene exhibit overlapping ocular and neurologic phenotypes. Common features include eye anomalies, dysmorphic facial features, seizures, feeding difficulties, developmental delay, intellectual disability, hypotonia, microcephaly, congenital cardiac defects, and hearing loss. Male patients may have micropenis and undescended testes, while female patients may experience delayed thelarche and menarche. Brain malformations include gyral hypoplasia, hippocampal dysplasia, reduced white matter volume, thin corpus callosum, and cerebellar hypoplasia. Other features such as spastic quadriplegia and neuroregression may be present in some patients. Additional multisystem phenotypes include craniofacial anomalies, hearing loss, genitourinary anomalies, feeding disorders, gastrointestinal anomalies, and skeletal anomalies. Severe neurologic impairment and cardiac anomalies can lead to early mortality.", "MENKE-HENNEKAM SYNDROME 1, Menke-Hennekam syndrome": "Patients with mutations in CREBBP (exon 30 or 31) exhibit a phenotype distinct from Rubinstein-Taybi syndrome (RSTS1). They do not have broad thumbs or characteristic facial features. However, they commonly experience developmental delay or intellectual disability, short stature, microcephaly, and variable facial characteristics such as short palpebral fissures, telecanthus, depressed nasal bridge, short nose, anteverted nares, short columella, and long philtrum. Autistic behavior and self-injurious behavior are observed in some cases. Other symptoms include recurrent upper airway infections, feeding problems, and impaired hearing. No major malformations are reported. Additional patients with MKHK1 also exhibit impaired intellectual development, autistic behavior, short stature, microcephaly, feeding problems, and vision and hearing impairment. Malformations such as cleft palate, congenital heart anomaly, renal anomaly, malrotation, and cryptorchidism are less common. Cerebral anomalies are seen in some patients, and facial features vary, but patients with mutations in a restricted 3-prime region resemble each other. Broad thumbs or angulated thumbs are not observed in any patients.", "NIZON-ISIDOR SYNDROME": "Patients with this rare genetic disorder exhibit global developmental delay, delayed walking and speech, impaired intellectual development (mild to moderate), and behavioral abnormalities including autism, ADHD, anxiety, stereotypic movements, and aggressive behavior. Dysmorphic features such as downslanting palpebral fissures, hypertelorism, and prominent nasal bridge are observed. Other variable features include feeding difficulties, gastroesophageal reflux, constipation, sleep disturbances, and distal hand or foot anomalies. Brain imaging abnormalities were observed in some patients, including corpus callosum abnormalities and cortical signal abnormalities. Seizures were present in one patient.", "OPITZ-KAVEGGIA SYNDROME": "Clinical features of the rare genetic disorder described in the texts include mental retardation, disproportionately large head, imperforate anus, congenital hypotonia, partial agenesis of the corpus callosum, short stature, joint contractures, seizures, characteristic facial appearance, gastrointestinal defects, congenital heart defects, sensorineural deafness, broad forehead, hypertelorism, long philtrum, open mouth, macrocephaly, broad thumbs and great toes, syndactyly, undescended testes, sagittal craniosynostosis, split-hand malformation, socially oriented attention-seeking behaviors, triangular face, micrognathia, low-set ears, short webbed neck, branchial cleft fistulae, hypoplastic penis with hypospadias, skeletal abnormalities, gastrointestinal dysmotility, language and communication deficits, inattention, anxiety, and impulsive behavior.", "GNAI1": "Rare genetic disorder: \n- Global developmental delay \n- Impaired intellectual development \n- Poor or absent speech \n- Hypotonia \n- Rare hypertonia \n- Poor motor coordination \n- Behavioral abnormalities \n- Sleep disturbances \n- Hypoplasia of the cerebrum \n- Nonspecific dysmorphic facial features \n- Skeletal anomalies \n- Seizures (in some cases) \n- Nonspecific brain imaging abnormalities \n- Dysmorphic features \n- Feeding difficulties \n- Hyperphagia with obesity (in some cases) \n- Constipation \n- Cryptorchidism (in some cases) \n- Cerebral palsy (in some cases) \n- Acute lymphoblastic leukemia (in some cases)", "NEURODEVELOPMENTAL DISORDER WITH BRAIN ANOMALIES AND WITH OR WITHOUT VERTEBRAL OR CARDIAC ANOMALIES": "Neurodevelopmental disorder with brain anomalies, vertebral/cardiac anomalies. Phenotype characteristics include: developmental disability, impaired intellectual development, cortical volume loss, dysgenesis of corpus callosum, colpocephaly, delayed myelination, thickened sulci, polymicrogyria, cerebellar volume loss, cerebellar hypoplasia, seizures, ophthalmoplegia, scoliosis, hypotonia, ventricular septal defect, atrial septal defect, skeletal anomalies, plagiocephaly, facial asymmetry, telecanthus, epicanthal folds, pectus excavatum, short stature, hypotonia, intramural thrombus, agenesis of corpus callosum, ventriculomegaly, colpocephaly, cerebellar dysplasia, intracranial cysts, polymicrogyria, heterotopia, chorioretinal lacunae, optic nerve coloboma, choreoathetosis, silent aspiration, scoliosis, dysmorphic features, precocious puberty, developmental delay, hypotonia, hypertelorism, pointed chin, midface hypoplasia, tooth agenesis, hypoplastic nails, Wolff-Parkinson-White syndrome.", "OGDEN SYNDROME": "Intellectual disability severe Gait disturbance Delayed gross motor development Poor coordination Delayed fine motor development obsolete Toe walking Autism Anxiety Delayed speech and language development Reduced eye contact Expressive language delay Repetitive compulsive behavior Receptive language delay Narrow palpebral fissure Narrow palpebral fissure Abnormal nasal bridge morphology Abnormal morphology of the nasal alae Broad philtrum Long philtrum Abnormality of upper lip vermillion Gastroesophageal reflux Hip dysplasia obsolete Toe walking Sparse anterior scalp hair Sleep disturbance X-linked inheritance", "MICROPHTHALMIA, SYNDROMIC 1": "Intellectual disability severe Gait disturbance Delayed gross motor development Poor coordination Delayed fine motor development obsolete Toe walking Autism Anxiety Delayed speech and language development Reduced eye contact Expressive language delay Repetitive compulsive behavior Receptive language delay Narrow palpebral fissure Narrow palpebral fissure Abnormal nasal bridge morphology Abnormal morphology of the nasal alae Broad philtrum Long philtrum Abnormality of upper lip vermillion Gastroesophageal reflux Hip dysplasia obsolete Toe walking Sparse anterior scalp hair Sleep disturbance X-linked inheritance", "INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 50, WITH BEHAVIORAL ABNORMALITIES": "Patients with heterozygous variants in the NAA15 gene exhibit a range of neurodevelopmental disorders. Common features include developmental delay/intellectual disability (DD/ID), delayed speech and language, and autism spectrum disorder (ASD). Other characteristics may include motor delay, behavior problems, poor growth, and nonspecific dysmorphic features. Seizures and abnormal brain imaging are not typically observed. Additionally, some patients may have a family history of mild intellectual disability. The phenotype is variable, but all patients show some degree of neurodevelopmental disability, including impaired motor abilities, intellectual disability, language impairment, and behavioral abnormalities. Dysmorphic facial features, poor overall growth, short stature, fine motor problems, hypotonia, seizures, feeding difficulties, and cardiac anomalies may also be present. The phenotype of patients with MRD50, caused by mutations in the NAA15 gene, is highly variable and includes global developmental delay, speech delay, autism spectrum disorder, ADHD, and seizures. The severity of symptoms can range from mild to severe, with some individuals showing improvement and normal cognition over time.", "MCCUNE-ALBRIGHT SYNDROME": "McCune-Albright syndrome (MAS) is characterized by abnormalities in the bony skeleton, skin, and endocrine system. Skeletal features include asymmetry, pathologic fractures, and deformities. Skin manifestations include large cafe-au-lait spots. Endocrine abnormalities include precocious puberty, hyperthyroidism, and excessive growth hormone secretion. MAS can also lead to malignancies, such as osteosarcoma. The syndrome shows phenotypic variation, with different clinical features and severity among individuals. Genetic analysis reveals mutations in the GNAS1 gene.", "SIN3B": "Clinical features of the rare genetic disorder described in the texts include: persistent ductus arteriosus, inguinal hernia, developmental delay, lymphedema, thrombocytopenia, midface hypoplasia, synophrys, ptosis, exotropia, short philtrum, thin upper lip, poor visual acuity, congenital nystagmus, sensorineural deafness, retinal dysplasia, pericardial effusion, hydrothorax, ascites, hypoalbuminemia, protein-losing enteropathy, poor postnatal growth, microcephaly, delayed psychomotor development, intellectual disability, behavioral disorders, facial dysmorphism, hearing and vision problems, cardiac abnormalities, immune and hematologic involvement, skeletal anomalies, genitourinary abnormalities, hypotonia, skin nevi, seizures, and brain abnormalities.", "MENTAL RETARDATION, AUTOSOMAL DOMINANT 40": "Rare genetic disorder: CHAMP1 gene mutation\n- Intellectual disability, severe speech impairment\n- Dysmorphic features: microcephaly, long face, open mouth, epicanthal folds, strabismus, upslanting palpebral fissures, short philtrum, tented upper lip, everted lower lip, high-arched palate, pointed chin, low-set ears\n- Additional features: hypotonia, feeding difficulties, delayed psychomotor development, hyperopia, decreased pain sensation, recurrent infections, ataxic gait, stereotypic movements, joint hypermobility\n- Brain imaging: normal or mild atrophy, delayed myelination, cerebellar cortical dysplasia\n- Behavioral abnormalities: autistic behavior, unmotivated laughter, aggressiveness\n- Ophthalmologic issues: hypermetropia, astigmatism, amblyopia, nystagmus\n- Associated conditions: seizures, failure to thrive, developmental delay, motor delay, gait abnormalities\n- Autism spectrum disorder traits, attention deficit-hyperactivity disorder, obsessive-compulsive disorder traits", "Meier-Gorlin syndrome": "Clinical features of this rare genetic disorder, known as Meier-Gorlin syndrome or ear-patella-short stature syndrome (EPS), include bilateral microtia (small ears), absent patellae, short stature, poor weight gain, and characteristic facial features. Other skeletal anomalies may include joint hyperextensibility, abnormal modeling of the glenoid fossas, and clinodactyly. Delayed bone age, proportional dwarfism, microcephaly, and craniofacial anomalies are also observed. Additional features may include deafness, congenital labyrinthine anomalies, and hypoplastic genitalia. Growth hormone deficiency and complications such as emphysema and hernia may also be present.", "MEIER-GORLIN SYNDROME 3, Meier-Gorlin syndrome": "Clinical features of this rare genetic disorder include short stature, very small external ears, cryptorchidism in males, bone defects (such as absent or nonossified patellae, femoral asymmetry, coxa valga, abnormal ribs, sacral hypoplasia, skull defect, abnormal development of sternum), micrognathia, microtia, hypoplasia of mammary glands, joint hyperextensibility, and delayed bone age. Other characteristics may include poor weight gain, dislocation of the knees, clubfeet, slender ribs and long bones, abnormal modeling of glenoid fossas, and clinodactyly. Some patients may also exhibit deafness, congenital labyrinthine anomalies, and hypoplastic genitalia.", "RUBINSTEIN-TAYBI SYNDROME 2, Rubinstein-Taybi syndrome": "Clinical features of Rubinstein-Taybi syndrome (RSTS) include mental retardation, broad thumbs and toes, facial abnormalities, juvenile glaucoma, talon cusps, pheochromocytoma, broad halluces, persistent fetal pads, shawl scrotum, frequent fractures, constipation, collapsible laryngeal walls, short upper lip, pouting lower lip, high slit-like palate, phenotypic overlap with Saethre-Chotzen syndrome, agenesis of the corpus callosum, iris coloboma, megacolon, pulmonary hypertension, mitral valve regurgitation, patent ductus arteriosus, cardiac abnormalities, increased risk of tumor formation, slipped capital femoral epiphysis, patellar dislocation, premature thelarche, immunodeficiency, orodental features, varicella meningoencephalitis, visual difficulties, keloids, eating problems, spinal curvature, joint laxity, dental problems, obesity, behavioral problems, and mild dysmorphic features. Incomplete RSTS may present with broad terminal phalanges, antimongoloid slant of the palpebral fissures, beaked nose, and broad thumbs. RSTS2 may have heavy and arched eyebrows, long eyelashes, a prominent nose, pouting lower lip, short broad thumbs, big toes, and square distal fingertips. EP300 gene mutations may cause mild RSTS with microcephaly, dyslexia, dyscalculia, and dysmorphic features.", "OPITZ GBBB SYNDROME, TYPE I, Opitz GBBB syndrome": "Clinical features of the rare genetic disorder, Opitz GBBB syndrome, include hypertelorism, neuromuscular defect of the esophagus and swallowing mechanism, hoarse cry, hypospadias, cryptorchidism, bifid scrotum, imperforate anus, and aspiration. Other features may include Usher syndrome, cleft lip, tracheotomy, anteverted nares, developmental delay, congenital heart disease, genitourinary anomalies, pituitary macroadenoma, cranial osteoma, laryngotracheoesophageal defects, limb defects, vermis hypoplasia or agenesis, and chylothorax.", "TEEBI HYPERTELORISM SYNDROME": "Clinical features of Teebi syndrome include:\n- Striking hypertelorism\n- Normal or slightly broad nasal tip\n- No craniosynostosis or abnormalities of the fingernails\n- More severe hypertelorism compared to CFNS and Aarskog syndrome\n- Absence of short stature and joint laxity\n- Equal occurrence in males and females\n- Prominent forehead\n- Mild antimongoloid slant\n- Long palpebral fissures\n- Heavy and broad eyebrows\n- Widow's peak\n- Broad and depressed nasal bridge\n- Short nose\n- Slightly small, broad hands\n- Mild interdigital webbing\n- Shawl scrotum\n- Male-to-male transmission\n- Variable extracranial abnormalities\n- Hypertelorism, bifid or broad nose, highly arched palate\n- Cleft lip and palate, Sprengel anomaly, pseudarthrosis of the clavicle, pectus excavatum, diaphragmatic hernia, broad first toe, longitudinal grooves of the nails, shawl scrotum, mild retardation\n- Sagittal craniosynostosis, absence of hypospadias in affected males\n- Hypertelorism, laryngotracheoesophageal manifestations, megalencephaly, broad prominent nasal root and bridge\n- Unusual form of GBBB syndrome, hypertelorism, laryngotracheoesophageal manifestations, megalencephaly, broad prominent nasal root and bridge\n- Prominent forehead, arched eyebrows, pronounced hypertelorism, long philtrum, mild interdigital webbing, fifth-finger clinodactyly, umbilical anomalies, hypotonia\n- Ptosis requiring surgical correction, umbilical hernia, heart murmur, iridochorioretinal colobomas\n- Craniosynostosis, no hypospadias in affected males\n- Prominent forehead, hypertelorism, exophthalmos, depressed nasal bridge, broad nasal tip, long philtrum, thin upper lip, short chin, low-set ears with preauricular fistulas, short neck, mild pectus excavatum, clinodactyly of the fifth fingers, pes adductus, natal teeth, umbilical hernia, ectopic right kidney\n- Hypertelorism, hypertelorism, arched eyebrows, prominent forehead, structural cardiac defects\n- Hypertelorism, natal teeth, 2-vessel cord, preauricular pit, micrognathia, hypersegmented lumbar vertebra, short stature, shawl scrotum, sagittal and coronal synostosis, ptosis, ventricular septal defect, dilated aortic root, normal IQ\n- Hypertelorism, natal teeth, atrial and ventricular septal defects, giant omphalocele, short stature, autism, behavioral issues\n- Ocular hypertelorism, cleft lip and palate, micrognathia, prominent forehead, broad nasal bridge, downslanting palpebral fissures, inguinal and umbilical hernias, metopic craniosynostosis, aortic stenosis, bicornuate uterus\n- Hypertelorism, prominent forehead, exophthalmos, long palpebral fissures, depressed nasal bridge, broad nasal tip, thin upper lip with everted lower lip, small chin, low-set ears with preauricular fistulas, short neck, mild pectus excavatum, clinodactyly of the fifth fingers, pes adductus, natal teeth, umbilical hernia, ectopic right kidney, normal psychomotor development\n- Hypertelorism, dysmorphic facial features, pacemaker for third-degree atrioventricular block, characteristic facial appearance, structural cardiac defects\n- Dysmorphic facial features, hypertelorism, broad nasal bridge, downslanting palpebral fissures, long or deep philtrum, arched or thick eyebrows, ear abnormalities, prominent forehead, bicornuate uterus, umbilical defect, congenital heart defect, developmental delays\n- Dysmorphic facial features, hypertelorism, broad nasal bridge, downslanting palpebral fissures, long or deep philtrum, arched or thick eyebrows, ear abnormalities, prominent forehead, bicornuate uterus, umbilical defect, congenital heart defect, developmental delays, CDH, cleft lip/palate, CNS defects", "CDC42": "Clinical features of the rare genetic disorder described in the texts include: persistent ductus arteriosus, inguinal hernia, developmental delay, lymphedema, thrombocytopenia, midface hypoplasia, synophrys, ptosis, exotropia, short philtrum, thin upper lip, poor visual acuity, congenital nystagmus, sensorineural deafness, retinal dysplasia, pericardial effusion, hydrothorax, ascites, hypoalbuminemia, protein-losing enteropathy, poor postnatal growth, microcephaly, delayed psychomotor development, intellectual disability, behavioral disorders, facial dysmorphism, hearing and vision problems, cardiac abnormalities, immune and hematologic involvement, skeletal anomalies, genitourinary abnormalities, hypotonia, skin nevi, seizures, and brain abnormalities.", "NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA AND VARIABLE INTELLECTUAL AND BEHAVIORAL ABNORMALITIES": "Patients with this rare genetic disorder exhibit a range of neurodevelopmental symptoms, including global developmental delay, hypotonia, delayed walking, speech and language delay, strabismus, and behavioral abnormalities. Some patients have a severe phenotype with additional features such as feeding difficulties, recurrent respiratory tract infections, microcephaly, and seizures. Others have a milder form of the disorder with less severe or absent symptoms. Brain imaging abnormalities, such as delayed myelination and cerebellar atrophy, are common in most patients.", "ARTHROGRYPOSIS, DISTAL, TYPE 5, Arthrogryposis, distal": "Distal Arthrogryposis Type 1A1:\n- Ulnar deviation, camptodactyly, absent flexion creases, overriding fingers\n- Metatarsus varus, talipes equinovarus, vertical talus, calcaneovalgus deformity\n- Intrafamilial variability, some patients with hip dislocation\n\nDistal Arthrogryposis Type 2B4:\n- Distal joint contractures at birth\n- Muscle weakness in proximal and distal muscles\n- Hearing impairment, high-arched palate, short neck, short stature, scoliosis\n\nDistal Arthrogryposis Type 5:\n- Ptosis, ophthalmoplegia, astigmatism, strabismus\n- Keratoconus, restrictive lung disease, pulmonary hypertension\n- Macular dystrophy, limited chest excursion, alveolar hypoventilation\n\nNote: These summaries are based on the provided texts and may not include all possible phenotype characteristics of the disorders.", "ARTHROGRYPOSIS, DISTAL, WITH IMPAIRED PROPRIOCEPTION AND TOUCH, Arthrogryposis, distal": "Distal Arthrogryposis Type 1A1: Ulnar deviation, camptodactyly, absent flexion creases, overriding fingers, metatarsus varus, talipes equinovarus, vertical talus, calcaneovalgus deformity, intrafamilial variability, hip dislocation, normal intelligence.\n\nDistal Arthrogryposis Type 2B4: Distal joint contractures, muscle weakness in proximal and distal muscles, hearing impairment, high-arched palate, short neck, short stature, contractures in proximal joints, smooth palms, scoliosis, type 1 fiber predominance in muscle biopsies.\n\nDistal Arthrogryposis Type 2B4 (Korean case): Camptodactyly, overlapping fingers, adducted thumbs, calcaneovalgus deformity, equinovarus deformity, facial dysmorphism, feeding difficulties, myopathy, bilateral sensorineural hearing loss.\n\nDistal Arthrogryposis Type 2B4 (female infant): Congenital distal arthrogryposis, dysmorphic facial features, myopathy, hypertelorism, prominent eyes, hypertrichosis, contractures of wrists, knees, fingers, toes, clubfoot, short nose, open mouth, bilateral sensorineural hearing loss.\n\nDistal Arthrogryposis Type 2B (Chinese family): Congenital contractures, ulnar deviation, camptodactyly, adducted thumbs, overlapping fingers, short stature, minor facial anomalies.\n\nDefects in touch and proprioception: Congenital hip dysplasia, finger contractures, foot deformities, severe progressive scoliosis, hypotonia, delayed motor development, reduced touch discrimination, proprioception, and vibratory sense, sensory axonal neuropathy.\n\nDAIPT: Hypotonia, poor feeding, respiratory insufficiency, delayed motor development, distal muscle weakness and atrophy, dysarthria, areflexia, scoliosis, contractures, myopathic facies, cognitive impairment.\n\nProgressive contractures with impaired touch sensation and proprioception: Severe deformities, short stature, scoliosis, decreased muscle strength, absent reflexes, abduction of first metacarpal bones, flexion contractures, eversion of feet, limited plantar flexion, luxation of radius.\n\nDAIPT (Turkish case): Hypotonia, hip dysplasia, distal laxity, contractures, difficulty feeding, myopathic changes, unsteady gait, elongated face, high-arched palate, distal laxity, flexion contractures, scoliosis, proprioception defect, axonal neuropathy.", "INTELLECTUAL DEVELOPMENTAL DISORDER WITH DYSMORPHIC FACIES, SEIZURES, AND DISTAL LIMB ANOMALIES": "Rare genetic disorder characterized by:\n- Significant global developmental delay since infancy\n- Absent speech, even in teenage patients\n- Early-onset seizures (generalized tonic-clonic, absence, myoclonic, atonic)\n- Variable severity and frequency of seizures\n- Hypotonia and poor motor development\n- Nonambulatory (except 1 patient)\n- Intrauterine growth retardation\n- Severe feeding difficulties, often requiring a feeding tube\n- Dysmorphic features (microcephaly, brachycephaly, flat occiput, arched eyebrows, long downslanting palpebral fissures, long nose, broad nasal root, smooth long philtrum, thin upper lip, retrognathia, high-arched palate, large protruding low-set ears, short neck)\n- Other congenital malformations (cardiac septal defects, sacral dimple, cryptorchidism, scoliosis, abnormalities of distal extremities)\n- Brain imaging abnormalities (nonspecific changes, cortical changes, white matter atrophy, enlarged ventricles, hypoplastic corpus callosum)\n- Clinical variability observed in some cases (mild to moderate intellectual disability, dysmorphic features, arachnodactyly, hyperextensibility of elbows)", "RETT SYNDROME": "Rett syndrome is a rare genetic disorder characterized by progressive encephalopathy, developmental stagnation, severe dementia, loss of purposeful hand use, jerky truncal ataxia, acquired microcephaly, spastic paraparesis, vasomotor disturbances, and epilepsy. Growth failure and metabolic abnormalities are common. Radiologic studies show metatarsal and metacarpal abnormalities. Neuropathologic findings include white matter disease and decreased dendritic trees. Proton magnetic resonance spectroscopy reveals axonal damage and astrocytosis. Cardiac abnormalities, such as prolonged QT interval, are observed. The Zappella variant is a milder form with preserved speech. Affected males have similar clinical features. Atypical Rett syndrome can present with mild mental retardation, autism, or a phenotype resembling Angelman syndrome.", "CARDIOFACIOCUTANEOUS SYNDROME 1, Cardiofaciocutaneous syndrome": "Clinical features of the cardiofaciocutaneous syndrome (CFC) include congenital heart defects, characteristic facial appearance (high forehead, bitemporal constriction, etc.), ectodermal abnormalities (sparse hair, hyperkeratosis), and growth failure. Other common features include pulmonary stenosis, atrial septal defect, and mental retardation. CFC syndrome shows overlap with Noonan syndrome, but can be distinguished by abnormal hair and hyperkeratotic lesions. Mutations in the BRAF gene are often found in CFC patients.", "CARDIOFACIOCUTANEOUS SYNDROME 3, Cardiofaciocutaneous syndrome": "Clinical features of the rare genetic disorder, CFC syndrome, include craniofacial abnormalities, ectodermal abnormalities (curly hair, hyperkeratosis), cardiac defects (pulmonic stenosis, hypertrophic cardiomyopathy), failure to thrive, skeletal demineralization, ocular abnormalities, seizures, developmental delay, hypotonia, heat intolerance, excessive sweating, and gastrointestinal dysmotility. Other common features include sparse hair, absent or sparse eyebrows, keratosis pilaris, nevi, short stature, and mental retardation. The disorder shows phenotypic overlap with Costello syndrome and Noonan syndrome, but is distinguished by the presence of abnormal hair and hyperkeratotic lesions. Mutations in the BRAF or MEK1 genes are associated with CFC syndrome.", "Cardiofaciocutaneous syndrome": "Clinical features of the cardiofaciocutaneous syndrome (CFC) include congenital heart defects, characteristic facial appearance (high forehead, bitemporal constriction, etc.), ectodermal abnormalities (sparse hair, hyperkeratosis), and growth failure. Common cardiac defects are pulmonic stenosis and atrial septal defect. CFC syndrome shows phenotypic overlap with Noonan syndrome, including short stature and keratosis pilaris. Other features include mental retardation, seizures, and gastrointestinal dysmotility. Mutations in the BRAF gene are often found in CFC patients. Craniofacial features include macrocephaly, high forehead, bitemporal narrowing, hypertelorism, and low-set ears. Dental phenotype includes malocclusion and high-arched palate.", "LEOPARD SYNDROME 3, LEOPARD syndrome": "Clinical features of the rare genetic disorder, LEOPARD syndrome, include generalized lentigines, cardiac changes (such as myocardial infarction and pulmonary stenosis), growth stunting, genital abnormalities (hypospadias, undescended testes), behavioral immaturity, and intellectual normality. Other characteristics may include left-sided obstructive cardiomyopathy, hypertrophic obstructive cardiomyopathy, respiratory insufficiency, thoracic deformities, pulmonary hypertension, ocular hypertelorism, mental and growth retardation, deaf mutism, hair loss, granular cell tumors, craniofacial anomalies, short and webbed neck, mitral and aortic valve dysplasia, cognitive deficits, neonatal hypotonia, sensorineural deafness, seizures, delayed puberty, reduced bone density, hyperkeratosis, cafe-au-lait spots, and facial features such as hypertelorism, depressed nasal bridge, and low-set and posteriorly rotated ears. LEOPARD syndrome shares phenotypic similarities with cardiofaciocutaneous syndrome-1.", "NOONAN SYNDROME 7, Noonan syndrome": "Noonan syndrome is characterized by poor neonatal growth, feeding difficulties, short stature, cognitive defects, skeletal anomalies, and hypotonia. Dysmorphic facial features include dolichocephaly, prominent forehead, hypertelorism, and low-set ears. Congenital cardiac defects, pulmonary stenosis, and hyperpigmented cutaneous lesions are also common. Other associated features include webbing of the neck, coarctation of the aorta, cryptorchidism, pterygium colli, myocardiopathy, and ophthalmologic abnormalities. Growth hormone therapy may be beneficial. Facial analysis technology can aid in diagnosis, but clinical evaluation is still necessary. Motor performance is often impaired, with decreased muscle strength and endurance.", "INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC, LUBS TYPE": "Rare genetic disorder: X-linked mental retardation with progressive central nervous system deterioration, hypotonia, myopathy, characteristic facies (downslanting palpebral fissures, hypertelorism, short nose), early mortality. Rett syndrome-like features, epilepsy, undescended testes, increased salivation, bruxism, communication difficulties, peripheral vasomotor disturbance. Severe mental retardation, axial hypotonia, spasticity, lack of speech, seizures, recurrent infections, facial hypotonia, large low-set ears, flat nasal bridge, skull asymmetry. MECP2 duplication/triplication: developmental delay, hypotonia, absent speech, recurrent infections, microcephaly, seizures, stereotypic hand movements, autistic-like features. MECP2 duplication syndrome: severe mental retardation, expressive language defects, autism, hypotonia, seizures, spasticity, endocrine abnormalities, psychiatric manifestations. Congenital hypoventilation syndrome: central hypotonia, hypoventilation, developmental delay, optic nerve hypoplasia, interstitial duplication of Xq28 including MECP2 gene.", "BARDET-BIEDL SYNDROME 6, Bardet-Biedl syndrome": "Clinical features of Bardet-Biedl syndrome include renal abnormalities, retinal dystrophy, polydactyly, mental retardation, mild obesity, hepatic fibrosis, and nephronophthisis. Other characteristics include hypertension, calyceal clubbing or blunting, calyceal cysts or diverticula, lobulated renal outlines, small testes and genitalia in men, menstrual irregularities and low estrogen levels in women, diabetes mellitus, vaginal atresia, hydrometrocolpos, hypogonadotropic hypogonadism, Hirschsprung disease, anosmia, peripheral sensation decrease, cone-rod dysfunction, and macular dystrophy. Bardet-Biedl syndrome shows phenotypic overlap with Laurence-Moon syndrome, and there is ongoing debate about their relationship. Different BBS genes are associated with subtle phenotypic differences, and a fifth BBS locus may exist.", "BARDET-BIEDL SYNDROME 5, Bardet-Biedl syndrome": "Clinical features of Bardet-Biedl syndrome include renal abnormalities, retinal dystrophy, polydactyly, mental retardation, mild obesity, hepatic fibrosis, nephronophthisis, hypertension, calyceal clubbing, calyceal cysts, lobulated renal outlines, small testes and genitalia in men, menstrual irregularities and low estrogen levels in women, diabetes mellitus, vaginal atresia, hydrometrocolpos, hypogonadotropic hypogonadism, situs inversus, Hirschsprung disease, anosmia, peripheral sensation decrease, cone-rod dysfunction, macular dystrophy. Phenotypic overlap with Laurence-Moon syndrome exists.", "BARDET-BIEDL SYNDROME 1, Bardet-Biedl syndrome": "Clinical features of Bardet-Biedl syndrome include renal abnormalities, retinal dystrophy, polydactyly, mental retardation, mild obesity, hepatic fibrosis, nephronophthisis, hypertension, calyceal clubbing, calyceal cysts, lobulated renal outlines, small testes and genitalia in men, menstrual irregularities and low estrogen levels in women, diabetes mellitus, vaginal atresia, hydrometrocolpos, hypogonadotropic hypogonadism, situs inversus, Hirschsprung disease, decreased corneal positive potential, anosmia, peripheral sensation decrease, cone-rod dysfunction, macular dystrophy, and taller affected offspring in BBS1 category.", "KLEEFSTRA SYNDROME 1, Kleefstra syndrome": "Clinical features of the rare genetic disorder include mental retardation, hypotonia, characteristic facial features (microcephaly, brachycephaly, hypertelorism, synophrys, midface hypoplasia, protruding tongue, eversion of the lower lip, prognathism), increased birth weight, childhood obesity, delayed motor function, congenital heart defects, seizures, micropenis, cryptorchidism, vesicoureteral reflux, tracheo-/bronchomalacia, gastroesophageal reflux, abnormal brain imaging, behavioral changes in adolescence (apathy, aggression, psychosis, autistic features, catatonia, bipolar mood disorder, regression in daily function and cognitive abilities), and disturbed sleep-wake pattern. Haploinsufficiency for the EHMT1 gene is responsible for the main phenotypic features.", "STICKLER SYNDROME, TYPE II, Stickler syndrome": "Stickler syndrome is a rare genetic disorder characterized by ocular, auditory, and orofacial features. It is associated with abnormal vitreous architecture, congenital nonprogressive myopia, and high-tone sensorineural hearing loss. Other common features include retinal detachment, cataracts, joint problems, and cleft palate. Variability in clinical manifestations exists, with different subtypes based on mutations in COL2A1 and COL11A1 genes. Diagnosis can be challenging due to phenotypic overlap with other syndromes. Treatment may involve cryotherapy, laser therapy, cleft palate repair, hearing aids, and joint replacements.", "STICKLER SYNDROME, TYPE I, Stickler syndrome": "Clinical features of the rare genetic disorder described in the texts include progressive myopia leading to retinal detachment and blindness, premature degenerative changes in joints, slight hypermobility, changes in vertebrae, hearing deficit, neonatal presentation with Pierre Robin syndrome, midface hypoplasia, absence of joint hyperextensibility or marfanoid habitus, skeletal abnormalities (mild flattening of epiphyses and irregularity of vertebral bodies), dumbbell-shaped femora and humeri, mitral valve prolapse, cataracts, aphakia, variability in symptoms and signs (including high myopia, mental retardation, marfanoid habitus), presence of missense mutation in COL11A1 gene, facial abnormalities (flat face, small mandible, cleft palate), hearing loss, joint problems, delays in diagnosis, and early onset osteoarthritis.", "STICKLER SYNDROME, TYPE IV, Stickler syndrome": "Clinical features of the rare genetic disorder, Stickler syndrome, include sensorineural hearing loss, myopia with vitreoretinopathy, epiphyseal dysplasia, retinal detachment, cleft palate, joint hypermobility, and skeletal abnormalities. Variability in symptoms and signs is observed, with some individuals presenting with high myopia and retinal detachment, while others exhibit cleft palate and characteristic facial changes. Treatment options include cryotherapy, laser therapy, cleft palate repair, and joint replacements.", "ROBINOW SYNDROME, AUTOSOMAL RECESSIVE 1, Robinow syndrome": "Clinical features of recessive Robinow syndrome include characteristic facial features, orodental abnormalities, hypoplastic genitalia, multiple rib and vertebral anomalies, short stature, mesomelic and acromelic brachymelia, hypertelorism, wide palpebral fissures, midface hypoplasia, large mouth, and hypogenitalism. Other associated features include hepatosplenomegaly, macrocephaly, calyectasia, vaginal atresia with cervical agenesis, webbing of the toes, epigastric hernia, intrauterine growth retardation, laxity of ligaments, joints, and skin, congenital heart disease, and endocrine dysfunction. The severity of craniofacial dysmorphology and intraoral features may differ between recessive and dominant forms of the syndrome.", "Robinow syndrome": "Clinical features of recessive Robinow syndrome include characteristic facial features, orodental abnormalities, hypoplastic genitalia, multiple rib and vertebral anomalies, short stature, mesomelic and acromelic brachymelia, hypertelorism, wide palpebral fissures, midface hypoplasia, large mouth, and hypogenitalism. Other associated features include hepatosplenomegaly, macrocephaly, calyectasia, vaginal atresia with cervical agenesis, webbing of the toes, epigastric hernia, intrauterine growth retardation, laxity of ligaments, joints, and skin, congenital heart disease, and endocrine dysfunction. The severity of craniofacial dysmorphology and intraoral features may differ between recessive and dominant forms of the syndrome.", "SIMPSON-GOLABI-BEHMEL SYNDROME, TYPE 1": "Clinical features of the rare genetic disorder include:\n- Distinctive facial appearance: large protruding jaw, widened nasal bridge, upturned nasal tip, enlarged tongue\n- Broad stocky appearance and broad, short hands and fingers\n- Clefting of the lower lip in some cases\n- Normal intelligence\n- Tall stature in some cases\n- Coarse facial features, micrognathia, short fingers, and dental abnormalities\n- Speech and psychosocial development problems\n- Congenital diaphragmatic hernia, ventricular septal defect, and other cardiac abnormalities\n- Polydactyly, syndactyly, and extra nipples\n- Splenomegaly, large dysplastic kidneys, and other organ abnormalities\n- Increased risk of neoplasia, including Wilms tumor\n- High perinatal and infant mortality rate\n- Cardiac arrhythmias and cardiovascular malformations\n- Choledochal cysts and other intraabdominal anomalies\n- Genital anomalies, such as cryptorchidism and hypospadias\n- Developmental delay and intellectual impairment\n- Autism spectrum disorder in some cases\n- Skewed X-inactivation in carrier females, leading to clinical expression of the disorder.", "MARBACH-RUSTAD PROGEROID SYNDROME": "Clinical features: progeroid appearance, delayed dentition with hypodontia, cerebellar intention tremor, microcephaly, protruding eyes, mandibular hypoplasia, prominent veins, paucity of subcutaneous fat, wormian bones, hypoplastic clavicles, crowded jaws with unerupted teeth, low appetite, inadequate nutrition, white matter hyperintensities, progressive hypomyelination, reduced bone mineral density, fractures, growth hormone therapy, echocardiographic abnormalities in patient 1, normal psychomotor development.", "INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 67": "Patients with this rare genetic disorder, caused by a mutation in the EIF3F gene, exhibit a range of clinical features. These include intellectual developmental disorder, impaired intellectual development, seizures, sensorineural hearing loss, short stature, microcephaly, behavioral problems, muscular hypo- or hypertonia, sleep issues, and epilepsy. Some patients also have subtle dysmorphic features, such as cleft lip and palate, anal stenosis, and small hands and feet. Developmental regression may occur in some individuals.", "EEF2": "Autosomal dominant pure spinocerebellar ataxia with slowly progressive gait ataxia, upper limb ataxia, and dysarthria. Pure cerebellar signs including trunk and limb ataxia, dysarthria, and irregular visual pursuit movements. Normal intelligence. MRI shows cerebellar atrophy sparing the pons and medulla. Loss of Purkinje cells in the cerebellar vermis.", "MULTIPLE CONGENITAL ANOMALIES-NEURODEVELOPMENTAL SYNDROME, X-LINKED": "Text 1 (Tripolszki et al, 2021): Severe multisystemic developmental disorder affecting 13 males in a large family. Clinical features include hypotonia, respiratory insufficiency, poor growth, feeding difficulties, global developmental delay, macrocephaly, hydrocephalus, craniosynostosis, deep-set eyes, hypertelorism, large forehead, flat nasal bridge, low-set ears, nystagmus, strabismus, hypospadias, cryptorchidism, limb and hand contractures, foot deformities, short stature, congenital cardiac defects, renal anomalies, seizures, visual impairment, enlarged ventricles, dysgenesis of the corpus callosum.\n\nText 2 (Beck et al, 2021): Developmental disorder with multiple congenital anomalies in 10 patients from 7 unrelated families. Common features include intrauterine growth retardation, poor postnatal growth, microcephaly, hypotonia, global developmental delay, impaired intellectual development, cardiac defects, genitourinary abnormalities, limb or skeletal anomalies, craniosynostosis, midface hypoplasia, retrognathia, low-set posteriorly rotated ears, hypertelorism, downslanting palpebral fissures, hypermetropia, strabismus, nystagmus, astigmatism, depressed nasal bridge, hirsutism, nonspecific renal anomalies, feeding difficulties, enlarged ventricles, thin or absent corpus callosum, pontocerebellar hypoplasia, polymicrogyria.", "NEUROFACIOSKELETAL SYNDROME WITH OR WITHOUT RENAL AGENESIS": "Clinical features of the rare genetic disorder described in the texts include severely delayed psychomotor development, partial agenesis of the corpus callosum, craniofacial dysmorphism (scaphocephaly, bitemporal hypertelorism, upslanting and asymmetric palpebral fissures, broad nasal root and tip, wide mouth, submucous cleft palate, low-set dysmorphic ears), disproportionate short stature with short limbs, kyphoscoliosis, flexion contractures of joints, brachydactyly of hands and feet, increased muscle tone, severely delayed motor and cognitive development, impaired vision, thoracic kyphoscoliosis with barrel-shaped vertebral bodies, subluxation of hip joint, delayed bone maturation, and ocular anomalies.", "NEURODEVELOPMENTAL DISORDER WITH PROGRESSIVE MICROCEPHALY, SPASTICITY, AND BRAIN IMAGING ABNORMALITIES": "Rare genetic disorder: Lethal microcephalic disorder with progressive microcephaly, delayed psychomotor development, lack of head control, ambulation, and speech development. Neurologic features: spastic quadriparesis, hyperreflexia, hypotonia, and early-onset seizures. Brain imaging shows enlarged ventricles, hypoplasia of corpus callosum, brainstem, and cerebellum. Increased plasma lysophosphatidylcholine (LPC) levels. Severe intellectual disability, absent speech, and spastic quadriparesis in another kindred. Brain imaging shows paucity of cerebral white matter. Syndromic neurodevelopmental disorder with microcephaly, hypotonia, poor feeding, global developmental delay, esotropic strabismus, mild facial dysmorphism, appendicular spasticity, and dystonia. Brain imaging shows enlarged ventricles and paucity of white matter. Primary microcephaly, severe developmental delay, axial hypotonia, increased deep tendon reflexes, seizures, talipes equinovarus, simplified gyral pattern, and abnormal corpus callosum in multiple patients.", "INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC, ARMFIELD TYPE": "Phenotype characteristics of the rare genetic disorder described in the texts include: \n- Mental retardation in males across multiple generations\n- Short stature, small hands, and feet\n- Seizures\n- Cleft palate and cataracts/glaucoma in some cases\n- Dysmorphic facial features such as prominent forehead, downslanting palpebral fissures, and micrognathia\n- Cognitive impairment requiring special schooling\n- Enlarged or asymmetric ventricles in brain imaging\n- Global developmental delay with variable severity\n- Speech and walking difficulties in some cases\n- Variable dysmorphic facial features with overlap\n- Additional features such as short stature, kyphoscoliosis, and clubfoot\n- Involvement of other systems, including imperforate anus and renal anomalies\n- Brain imaging abnormalities, including decreased white matter and small corpus callosum.", "NEURODEVELOPMENTAL DISORDER WITH OR WITHOUT AUTISTIC FEATURES AND/OR STRUCTURAL BRAIN ABNORMALITIES": "Patients with a rare genetic disorder caused by de novo heterozygous frameshift mutations in the NOVA2 gene exhibit global developmental delay, delayed motor milestones, hypotonia, and feeding difficulties. Most achieve walking by age 4, but some may be unable to walk. They have impaired intellectual development with poor or absent speech and language acquisition. Behavioral abnormalities, including autistic features, stereotypic movements, and poor social interaction, are common. Some patients also experience seizures. Growth is poor, with small head circumference, and mild dysmorphic features may be present. Brain imaging shows variable structural abnormalities.", "NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA AND CEREBELLAR ATROPHY, WITH OR WITHOUT SEIZURES": "NEDHCAS is a rare genetic disorder characterized by global developmental delay, hypotonia, delayed walking, intellectual disability, poor language development, seizures, dysmorphic facial features, and progressive cerebellar atrophy or hypoplasia. Other features include poor fine motor coordination, nystagmus, abnormal saccades, spasticity, involuntary movements, and dental anomalies. Patients may also have microcephaly, respiratory complications, and early mortality.", "DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 83": "DEE83 is a rare genetic disorder characterized by early onset seizures, developmental delay, and various physical abnormalities. Most affected children present with seizures in infancy, which are often difficult to control. They also exhibit profound global developmental impairment, including delayed motor milestones and absent speech. Ocular anomalies, constipation, recurrent infections, and dysmorphic features may be present. Brain imaging typically shows generalized anomalies. The disorder is often seen in consanguineous families.", "SKELETAL DYSPLASIA, MILD, WITH JOINT LAXITY AND ADVANCED BONE AGE": "Clinical features of the rare genetic disorder described in the texts include: \n- Micromelia and brachydactyly\n- Round face with midface hypoplasia\n- Mild joint laxity and pes planus\n- Dysmorphic facial features such as flat nasal bridge, short nose, and microretrognathia\n- Radiographic findings of flat acetabular roofs, metaphyseal beaking, and coronal and sagittal clefting of the vertebrae\n- Mild advanced carpotarsal bone age\n- Recurrent episodes of Bell palsy in the mother\n- Short stature and hypermobile joints\n- Genua valga and winged scapulae\n- Radiographic findings of flat acetabular roof and bilateral concave tibial deviation\n- Macrocephaly and facial dysmorphism\n- Mild scoliosis, pectus excavatum, and brachydactyly\n- Language delay and ADHD\n- Mild ventriculomegaly and reduced volumes of the hippocampi and cavum vergae\n- Neonatal respiratory distress\n- Mosaic trisomy 8 with blended phenotype and discordant features.", "NEURODEVELOPMENTAL DISORDER WITH EPILEPSY, SPASTICITY, AND BRAIN ATROPHY": "Text 5: Severe neurodevelopmental disorder with hypotonia, spasticity, delayed milestones, feeding difficulties, seizures, dysmorphic features, scoliosis, contractures, and brain atrophy.\n\nText 1: Severe encephalopathy with microcephaly, seizures, spastic tetraplegia, abnormal movements, cataracts, visual impairments, and brain atrophy.\n\nText 2: Progressive encephalopathy with growth delay, microcephaly, dystonia, spasticity, cerebral atrophy, and elevated lactate and CPK levels.\n\nText 3: Neurodevelopmental disorder with delayed milestones, growth delay, microcephaly, spasticity, seizures, hearing loss, brain abnormalities, and elevated CPK levels.", "NEURODEVELOPMENTAL DISORDER AND STRUCTURAL BRAIN ANOMALIES WITH OR WITHOUT SEIZURES AND SPASTICITY": "Rare genetic disorder: \n- Developmental delay\n- Seizures\n- Diffuse brain atrophy on MRI\n- Profound global developmental delay\n- Cortical blindness with poor visual attention\n- Wheelchair-bound with spasticity, hypertonia\n- Absent speech, lack of purposeful hand movements\n- Progressive microcephaly\n- Scoliosis, failure to thrive, severe hip dysplasia\n- EEG abnormalities (sharp waves, spikes, slow waves)\n- Enlarged ventricles, cerebellar hypoplasia, thin corpus callosum\n- Progressive brain atrophy, severe reduction of white matter volume\n- Family history of affected deceased siblings\n- Developmental regression\n- Microcephaly, lack of visual fixation, axial hypotonia, poor feeding\n- Refractory severe seizures\n- Reduced brain volume, absent myelination, enlarged ventricles\n- Hypoplastic optic nerves, hypoplastic corpus callosum\n- Intrauterine growth retardation, feeding problems\n- Deafness, blindness with optic nerve atrophy\n- Inability to walk, sit, or speak\n- Impaired myelination, cortical/subcortical atrophy\n- Variable dysmorphic features\n- Abnormal muscle tone with spasticity\n- Abnormal brain imaging (enlarged ventricles, brain atrophy, delayed myelination)\n- Microcephaly, spastic quadriparesis, no language, abnormal eye movements, lissencephaly\n- Mild intellectual disability, difficulty in social interactions\n- Hypoplasia of optic nerves, dysmorphic features\n- Able to attend special schooling", "PACHYGYRIA, MICROCEPHALY, DEVELOPMENTAL DELAY, AND DYSMORPHIC FACIES, WITH OR WITHOUT SEIZURES": "PAMDDFS is a rare genetic disorder characterized by hypotonia, global developmental delay, progressive microcephaly, and dysmorphic features. Seizures, impaired intellectual development, and ocular anomalies are common. Brain imaging shows malformations of cortical development. Premature birth may contribute to additional imaging anomalies. One patient had a more severe phenotype and carried a de novo duplication of 2q23.1, suggesting a dual genetic diagnosis.", "NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, ARTHROGRYPOSIS, AND STRUCTURAL BRAIN ANOMALIES": "Severe congenital neurodevelopmental disorder with high mortality rate before 12 months. Common features include intrauterine growth retardation, microcephaly, respiratory distress, arthrogryposis, developmental delay, limited movement, microcephaly, hypo/hypertonia, breathing/swallowing difficulties, seizures, congenital heart defects. Neuroimaging shows abnormal brain structure. Dysmorphic features include receding forehead, short palpebral fissures, large ears, low-set ears, cleft lip, short neck, clenched hands, rocker-bottom feet, clubfeet. Some individuals achieve delayed independent walking and limited speech.", "AGENESIS OF CORPUS CALLOSUM, CARDIAC, OCULAR, AND GENITAL SYNDROME": "Clinical features of the rare genetic disorder associated with mutations in the CDH2 gene include developmental delay/intellectual disability, callosal malformations, cardiac and ocular abnormalities, and characteristic facial dysmorphisms. Other common characteristics include agenesis of the corpus callosum, hypothalamic adhesion, periventricular nodular heterotopia, and congenital cardiac defects. Neurological features may include seizures and cognitive delays. Dysmorphic features include broad forehead, downslanting palpebral fissures, low-set ears, thin upper lip, and pointed chin. Other features may include shoulder deformities, genital anomalies, and macrocephaly.", "NEURODEVELOPMENTAL DISORDER WITH NONSPECIFIC BRAIN ABNORMALITIES AND WITH OR WITHOUT SEIZURES": "Neurodevelopmental disorder with developmental delay, impaired intellectual development, autism spectrum disorder, attention deficit, stereotypic behavior, and structural brain abnormalities. Speech delay, variable IQ levels, seizures, dysmorphic features (mainly upslanting palpebral fissures), hypotonia, hyperextensible joints, ataxia, kyphosis/scoliosis. Less common features include neonatal hyperbilirubinemia, sacral dimple, syringomyelia, and eye movement abnormalities.", "NEURODEVELOPMENTAL, JAW, EYE, AND DIGITAL SYNDROME": "Individuals with mutations in the FBXW11 gene exhibit a range of overlapping phenotypes, including neurodevelopmental delay, speech delay, autistic and/or stereotypical behaviors, psychiatric features, and micro- or macrocephaly. MRI data showed corpus callosal hypoplasia, dilated ventricles, and white matter atrophy. Digital anomalies include brachydactyly, polysyndactyly, widened interdigital spaces, camptodactyly, and underdeveloped thenar musculature. One patient had Noonan syndrome, while another had pulmonary stenosis. There is phenotypic overlap with features reported in a boy with a deletion on chromosome 5q35 that included the FBXW11 gene.", "NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA AND AUTISTIC FEATURES WITH OR WITHOUT HYPERKINETIC MOVEMENTS": "Children with this rare genetic disorder exhibit axial hypotonia, global developmental delay, severely impaired intellectual development, and poor or absent language skills. They also display behavioral abnormalities consistent with autism spectrum disorder, including stereotypic movements and poor communication and social skills. Motor skills are delayed, with some patients unable to walk or perform purposeful hand movements. Some individuals may also experience visual impairment and develop an involuntary hyperkinetic movement disorder with chorea and dystonia. In severe cases, deep brain stimulation may be necessary.", "SPONDYLOEPIMETAPHYSEAL DYSPLASIA, SPONASTRIME TYPE": "Clinical features of sponastrime dysplasia include short-limb dwarfism, moderate deformity of vertebral bodies, striated metaphyses, saddle nose, frontal bossing, large head, normal intelligence, short stature in family members, depressed nasal bridge, midface hypoplasia, epicanthal folds, increased lumbar lordosis, joint laxity, limitation in elbow extension or rotation, scoliosis, coxa vara, avascular necrosis of the hip, subglottic stenosis, bronchotracheomalacia, and characteristic radiographic changes in the vertebrae and long bones. Additional findings may include short dental roots, cataracts, hypogammaglobulinemia, and TONSL gene mutations.", "NEURODEVELOPMENTAL DISORDER WITH SEIZURES AND SPEECH AND WALKING IMPAIRMENT": "Neurodevelopmental disorder with global developmental delay, delayed walking and speech/language development, behavioral problems, hypotonia, walking difficulties, seizures, dysmorphic features (deep-set eyes, prominent infraorbital creases, thin upper lip, etc.), constipation, sacral dimples, easy bruising, skin sensitivity, and low IgA and IgG levels.", "HOLOPROSENCEPHALY 5": "Holoprosencephaly (HPE) is a common brain anomaly associated with deletions and duplications of chromosome 13. Patients with HPE often have major congenital malformations, including brain anomalies and digital anomalies. ZIC2 mutations are a common cause of HPE without facial malformation. Patients with HPE5, caused by ZIC2 mutations, commonly have alobar or semilobar HPE and display a subtle facial phenotype. Other features include hydrocephalus, neural tube defects, skeletal anomalies, and ophthalmologic abnormalities. Rhombencephalosynapsis may be related to HPE, but no ZIC2 mutations were found in cases of rhombencephalosynapsis. Ophthalmologic anomalies, such as hyperopia and microcornea, are common in patients with HPE.", "TRICHOTHIODYSTROPHY 5, NONPHOTOSENSITIVE": "Clinical features of the rare genetic disorder include: intrauterine growth restriction, progressive microcephaly, profound intellectual disability, genital anomalies (absent or rudimentary testes and microphallus), severe linear growth failure, partial absence of the posterior portion of the corpus callosum, cerebellar hypoplasia, Dandy-Walker malformation, minimal muscle mass, reduced subcutaneous fatty tissue, aged facial appearance, high forehead, broad mouth with widely spaced primary teeth, prominent chin, ataxic broad-based gait, minimal body hair, sparse and slow-growing scalp hair and eyebrows, tiger-tail pattern in hair, sulfur deficiency in hair amino acid content, trichothiodystrophy, major structural anomalies (short esophagus, ureteric obstruction), recurrent infections, IgG1 subclass deficiency, panhypopituitarism, retinal dystrophy, optic nerve hypoplasia, photosensitivity, nucleotide excision repair deficiency, short stature, delayed walking and speech, learning difficulties, refractory seizures, hypogammaglobulinemia, hypergonadotropic hypogonadism, duodenal strictures, nonphotosensitive trichothiodystrophy, sparse and brittle hair, thin eyebrows, dry skin, hypoplasia of the corpus callosum, focal trichorrhexis nodosa, short stature in family members, facial anomalies (triangular face, broad forehead, low-set ears, wide mouth), ambiguous genitalia with severe hypospadias, absent eyebrows and eyelashes, mottled dry skin, microcephaly, dysmorphic craniofacial features, adrenal hypoplasia, agenesis of the posterior corpus callosum.", "BEAULIEU-BOYCOTT-INNES SYNDROME": "Text 1: Patients showed developmental delay, distinctive facial features (tall forehead, deep-set eyes, long nose), mild renal malformations, cardiac defects, gynecologic involvement, dental caries, cognitive weakness in mathematics and spatial reasoning.\n\nText 2: Patient had imperforate anus, undescended testes, heart defects, growth delay, broad forehead, low-hanging columella, delayed development, and dysmorphic facial features.\n\nText 3: Patients had microcephaly, intellectual disability, cardiac anomalies, hearing loss, dental anomalies, corpus callosum dysgenesis, and dysplasia.\n\nText 4: Patient had short soft palate, anterior displacement of the anus, trigger thumb, hip dislocation, kidney dysplasia, optic hypoplasia, hydrocephalus, cerebellar hypoplasia, and vertebral anomalies.\n\nText 5: Patients had intrauterine growth restriction, micropenis, short corpus callosum, neonatal hypotonia, cognitive impairment, upper limb stereotypies, and dysmorphic features.\n\nText 6: Patient had cleft palate, micrognathia, choanal atresia, heart defects, hydrocephalus, developmental delays, and various complications (exotropia, hearing loss, seizures, lung disease, pulmonary hypertension).", "CULLER-JONES SYNDROME": "Clinical features of the rare genetic disorder described in the texts include:\n- Hypopituitarism\n- Bilateral postaxial polydactyly\n- Cryptorchidism\n- Microphallus\n- Empty sella on brain imaging\n- Aplasia of the pituitary\n- Growth failure\n- Delayed psychomotor development\n- Early-onset seizures\n- Pituitary hormone deficiencies\n- Short stature\n- Delayed bone age\n- Hypogonadotropic hypogonadism\n- Low thyroid-stimulating hormone\n- Hypoplastic anterior pituitary\n- Ectopic posterior pituitary\n- Diminished brain size with asymmetry of cerebral hemispheres\n- High-pitched voice\n- Cleft lip and palate\n- Flat nasal bridge\n- Partial ACTH deficiency\n- ADH deficiency with diabetes insipidus\n- Lack of posterior pituitary on brain imaging\n- Truncating mutations in the GLI2 gene\n- Missense variants of unknown significance in the GLI2 gene\n- Normal facial features or nondysmorphic appearance\n- Midface hypoplasia\n- Cleft lip/palate\n- Hypotelorism\n\nThe phenotype of this disorder typically includes anterior pituitary anomalies and postaxial polydactyly, but not all individuals with pathogenic GLI2 mutations have both findings. The disorder does not typically include holoprosencephaly (HPE).", "NEURODEVELOPMENTAL DISORDER WITH CATARACTS, POOR GROWTH, AND DYSMORPHIC FACIES": "Patients with this rare genetic disorder exhibit neurodevelopmental impairment, including severely impaired intellectual development and absent language. They also have short stature, with some patients experiencing walking difficulties. Additional features include cataracts, frontal bossing, hypertelorism, dolichocephaly, pectus abnormalities, and irregularly implanted and overlapping toes. Some patients have renal dysplasia or congenital heart defects. Brain imaging is mostly normal, although some patients may show nonspecific abnormalities.", "ALSTROM SYNDROME": "Clinical features of Alstrom syndrome include retinitis pigmentosa, deafness, obesity, and diabetes mellitus. Other common characteristics include blindness, hyperuricemia, elevated serum triglyceride levels, dilated cardiomyopathy, acanthosis nigricans, hepatic dysfunction, and growth retardation. Additional features may include hypothyroidism, asthma, scoliosis, and developmental delay. The syndrome is often diagnosed in childhood, with severe infantile retinal dystrophy and absent or attenuated electroretinogram responses. It is important to consider Alstrom syndrome in cases of infantile cone and rod retinal dystrophy, especially if accompanied by cardiomyopathy or obesity. Liver involvement, renal anomalies, and urologic abnormalities have also been reported.", "THREE M SYNDROME 2": "Clinical features of 3M syndrome include low birth weight, short stature, malar hypoplasia, anteverted nostrils, long philtrum, pointed full chin, short broad neck, broad chest with transverse grooves, hyperlordosis, prominent premaxilla, hypoplastic maxilla, thick patulous lips, high-arched palate, delayed eruption of teeth, slender long bones and ribs, narrow pelvis, foreshortened vertebral bodies, prominent heels, frontal bossing, midface hypoplasia, and triangular face. Growth hormone treatment may be used but may not always result in significant height gain.", "SKIN CREASES, CONGENITAL SYMMETRIC CIRCUMFERENTIAL, 2": "Clinical features of the rare genetic disorder include: increased number of deep skin creases, mental retardation, seizures, cleft palate, elongated face, hypertelorism, epicanthal folds, upslanting palpebral fissures, microphthalmia, wide nasal bridge, absent maxillary incisors, decay of several teeth, low-set posteriorly rotated ears with thick overfolded helices, short neck, mild pectus excavatum, widely spaced nipples, ventral penile curvature with hypospadias, hypoplastic scrotum, undescended testes, diffuse osteopenia, hypoplastic vermis, hypoplastic corpus callosum, atonic dilation of ventricles, left ureterocele, bilateral mild deafness, flat midface, broad nasal bridge, microstomia, moderate developmental delay, absence of expressive language, hypoplastic scrotum, hypospadias, hypoplasia of the corpus callosum, mildly dilated lateral ventricles, flat face, low-set small posteriorly rotated ears with overfolded helices and upturned ear lobes, microstomia, and mild intellectual disability.", "SCHINZEL-GIEDION MIDFACE RETRACTION SYNDROME": "Clinical features of Schinzel-Giedion syndrome include severe midface retraction, multiple skull anomalies, congenital heart defects, hydronephrosis, clubfeet, hypertrichosis, and increased density of long tubular bones. Other reported abnormalities include telangiectases, hypoplasia of dermal ridges, genital anomalies, broad ribs, hypoplasia of distal phalanges, ventriculomegaly, intraventricular bands, subependymal pseudocysts, sacrococcygeal teratoma, hepatoblastoma, primitive neuroectodermal tumor, syndactyly, brain anomalies, intractable epilepsy, spasticity, growth and developmental retardation, hypothyroidism, diabetes insipidus, seizures, hearing loss, camptodactyly, dysplastic sternum, small brain, hypoplastic corpus callosum, steatosis of liver, lipid vacuolization of adrenals, progressive neurodegeneration, megacalycosis, infantile spasms, hypsarrhythmic activity, alacrimia, corneal hypoesthesia, tuning-fork malformation of stapes, splenopancreatic fusion, very short epiglottis, vocal cord paralysis, radioulnar synostosis, and possible hypothyroidism.", "POLR3GL": "Clinical features of the rare genetic disorder described in the texts include: \n- Short stature\n- Localized endosteal hyperostosis primarily in the axial skeleton\n- Oligodontia (missing teeth)\n- Clubfeet\n- 2-3 toe syndactyly (fusion of toes)\n- Dysmorphic facial features such as upslanting palpebral fissures, beaked nose, thin lips with downturned corners, and flat philtrum\n- Delayed puberty\n- Delayed motor development\n- Wheelchair use\n- Congenital spastic diplegia (inability to walk)\n- Foot pain and lumbar disc-related back pain\n- Urinary incontinence\n- Varus deformity of the feet\n- High nasal bridge with long columella\n- Broad nasal tip\n- Downturned mouth\n- Retrognathia (receding chin)\n- Soft skin\n- Hyperextensible joints\n- Hypotonia (low muscle tone)\n- Progeria-like features (in one case)\n- Large anterior fontanel\n- Hypertelorism (wide-set eyes)\n- Proptosis (bulging eyes)\n- Midface hypoplasia (underdeveloped midface)\n- Low-set posteriorly rotated ears\n- High-arched palate\n- Ulnar deviation and contractures of fingers\n- Short toes\n- Axial hypotonia\n- Hypoplastic labia minora\n- Infantile hemangiomas\n- Bicuspid aortic valve\n- Atrial septal defect type II\n- Choanal atresia (blockage of nasal passage)\n- Stenosis of the aperture of the pyriform sinus\n- Mild ventriculomegaly (enlarged brain ventricles)\n- Communicating hydrocephalus (in one case)\n- Microcephaly (small head size)\n- Global developmental delay\n- Protruding forehead with prominent scalp veins\n- Patent anterior fontanel (open skull fontanel)", "EHLERS-DANLOS SYNDROME, SPONDYLODYSPLASTIC TYPE, 3": "Clinical features of the 'spondylocheiro dysplastic form of Ehlers-Danlos syndrome' described by Giunta et al (2008) include postnatal growth retardation, moderate short stature, protuberant eyes with bluish sclerae, finely wrinkled palms, atrophy of the thenar muscles, and tapering fingers. Patients also exhibited thin, hyperelastic skin and hypermobile small joints resembling Ehlers-Danlos syndrome. Radiologic features included mild to moderate platyspondyly, osteopenia of the spine, small ileum, flat proximal femoral epiphyses, and broad metaphyses in various joints.", "MENTAL RETARDATION, AUTOSOMAL RECESSIVE 5": "Rare genetic disorder: Moderate to severe mental retardation, mild dysmorphic features (microcephaly, long and narrow face, bushy eyebrows with synophrys, hypotelorism, large nose with long columella and hypoplastic alae nasi, short philtrum, full upper lip), short stature, later onset of muscular hypertonia and spasticity, delayed psychomotor development with limited speech, dysarthria, poor somatic growth, distal myopathy, broad-based gait with pes cavus and tight Achilles tendons, strabismus, intermittent esotropia, increased LDH and serum creatine kinase, low birth weight, progressive microcephaly, speech delay, blepharophimosis, hypertelorism, broad nasal bridge, smooth philtrum, downturned upper lip, dental anomalies, axial hypotonia, eczema, seizures, sparse hair, self-stimulation, autistic features. Phenotypic similarities to Dubowitz syndrome.", "FRASER SYNDROME 1, Fraser syndrome": "Clinical features of the rare genetic disorder described include:\n- Cryptophthalmos (abnormal development of the eyelids)\n- Absent or malformed lacrimal ducts\n- Middle and outer ear malformations\n- High palate\n- Cleavage along the midplane of nares and tongue\n- Hypertelorism (wide-set eyes)\n- Laryngeal stenosis (narrowing of the larynx)\n- Syndactyly (fusion of fingers or toes)\n- Wide separation of symphysis pubis (pelvic bone)\n- Displacement of umbilicus and nipples\n- Malformed kidneys\n- Fusion of labia and enlargement of clitoris\n- Bicornuate uterus and malformed fallopian tubes\n- Possible association with consanguinity in some cases\n- Variable clinical presentation and phenotypic variation", "MITOCHONDRIAL DNA DEPLETION SYNDROME 13 (ENCEPHALOMYOPATHIC TYPE)": "Rare genetic disorder: severe mitochondrial encephalomyopathy. Clinical features include global developmental delay, hypotonia, persistent lactic acidosis, microcephaly, craniofacial abnormalities, congenital cataracts, cerebral atrophy, cerebellar hypoplasia, decreased COX activity, reduced basal respiration, decreased ATP synthesis, loss of mitochondrial membrane potential, mtDNA depletion, fragmented mitochondrial network, severe psychomotor delay, failure to thrive, swallowing difficulties, muscle wasting, truncal ataxia, seizures, choreoathetoid movements, hypospadias, neutropenia, scoliosis, small feet, dysmorphic facial features, hypertrophic cardiomyopathy, global brain atrophy, thin corpus callosum, altered signals in white matter, decreased mtDNA content, and fragmented mitochondrial network.", "CARDIOSPONDYLOCARPOFACIAL SYNDROME": "Clinical features of the rare genetic disorder include congenital mitral regurgitation, congenital perceptive deafness, fusion of cervical vertebrae and carpal/tarsal bones, freckling of the face and iris, short stature, hypotonia, failure to thrive, growth retardation, facial dysmorphism, congenital cardiac defects, shortened extremities, delayed carpal bone age, inner ear malformation, soft/dystrophic skin, extreme joint hypermobility, upper gastrointestinal dysmotility, and abnormal postsurgical scars. Psychomotor development is generally normal.", "GLYCOSYLPHOSPHATIDYLINOSITOL BIOSYNTHESIS DEFECT 11": "1. Japanese male infant with delayed development, tonic seizures, and dysmorphic facial features. Elevated serum alkaline phosphatase and reduced levels of GPI-APs.\n2. Second-degree cousins with hypotonia, delayed psychomotor development, seizures, and mildly decreased GPI-APs. Normal brain imaging.\n3. Sib fetuses with Dandy-Walker malformation, hydronephrosis, dysplastic kidneys, genital hypoplasia, and diaphragmatic hernia.\n4. Chinese boy with pneumonia, facial features including wide nasal bridge and tented lips, developmental delay, elevated serum alkaline phosphatase, and abnormal brain MRI.\n5. Egyptian girl with global developmental delay, seizures, hypsarrhythmia on EEG, treated with ACTH, hypotonia, intellectual impairment, facial features including low frontal hairline and wide nasal bridge, skeletal features, and elevated serum alkaline phosphatase.", "STEEL SYNDROME": "Clinical features of the rare genetic disorder, Steel syndrome, include dislocated hips and radial heads, carpal coalition, short stature, talipes cavus, anomalies of the cervical spine, scoliosis, cavus feet, and characteristic facies. Other features may include syndactyly, clubfoot, genu valgum, developmental delay, hearing loss, and spinal degeneration. The disorder is more prevalent in individuals of Puerto Rican ancestry.", "KABUKI SYNDROME 2, Kabuki syndrome": "Clinical features of Kabuki syndrome include:\n- Peculiar facial characteristics: eversion of lower lateral eyelid, arched eyebrows, depressed nasal tip, prominent ears.\n- Skeletal anomalies: brachydactyly V, spinal deformity, sagittal cleft vertebrae.\n- Dermatoglyphic abnormalities: increased digital ulnar loop, hypothenar loop patterns, absence of digital triradius c and/or d, fingertip pads.\n- Mild to moderate mental retardation.\n- Postnatal growth deficiency.\n- Fetal finger pads.\n- Congenital heart defects.\n- Early breast development in some infant girls.\n- Variable expressivity and inheritance pattern.\n- Other associated features: cleft palate, diaphragmatic hernia, anorectal anomalies, hearing loss, immune deficiency, hair abnormalities, renal and hepatic anomalies, ocular abnormalities, behavioral phenotype, hypogammaglobulinemia, microcephaly, obesity, seizures, developmental delay, feeding problems, genitourinary anomalies, palate and dental anomalies, hearing loss, and strabismus.", "SHORT STATURE, ONYCHODYSPLASIA, FACIAL DYSMORPHISM, AND HYPOTRICHOSIS": "Clinical features of the rare genetic disorder include:\n- Short stature of prenatal onset\n- Rhizomelic limb shortness, particularly affecting the upper limbs\n- Unusual face with relative macrocephaly, frontal balding, midface hypoplasia, small nose, macrostomia with downturned corners of the mouth, gingival hypertrophy, and hypoplasia or absence of the clitoris\n- Delayed ossification of the proximal humeral and femoral epiphyses\n- Delayed gross motor development\n- Small hands with short rectangular fingers and hypoplastic fingernails\n- Triangular-shaped face with protruding forehead, deep-set eyes, large nose, and pointy chin with retrognathia\n- Irregularly positioned and crowded teeth with severe dental caries\n- Severe disproportionate short stature\n- Normal cognitive abilities and lack of neurologic deficits\n- Prominent nose, high-pitched voice, relatively small ears, clinodactyly, brachydactyly, small hands, hypoplastic fingernails, waddling gait, and sparse hair after puberty\n- Short long bones, especially femurs and humeri, with mild metaphyseal changes and very short femoral necks\n- Development of type 2 diabetes mellitus and oligo-azoospermia in affected males\n- Tanner stage III secondary sexual characteristics in affected females\n- Dental anomalies including cone-shaped, widely spaced teeth, missing teeth, and irregularly positioned, crowded teeth with severe dental caries\n- Primordial dwarfism with distinctive facial dysmorphism, including elongated triangular face, high forehead, hypertelorism, depressed nasal bridge, broad upturned nose, long philtrum, and posteriorly rotated low-set ears\n- Normal psychomotor development in some cases, while others have severe global developmental delay and hypotonia\n- Skeletal abnormalities including diffuse osteopenia, epiphyseal hypoplasia, and short and broad carpals, metacarpals, tarsals, and metatarsals.", "SPINOCEREBELLAR ATAXIA 42, EARLY-ONSET, SEVERE, WITH NEURODEVELOPMENTAL DEFICITS": "Severe neurodevelopmental disorder with cerebellar atrophy. Presents with severe hypotonia, delayed psychomotor development, intellectual disability, and absent speech. Poor eye contact and head control. Axial hypotonia and variable limb spasticity, hypertonia, or dystonia. Unable to walk independently. Cerebellar ataxia and dysmetria. Oculomotor apraxia and strabismus in three patients, hyperopia in one. Dysmorphic features include small/upslanted palpebral fissures, hypertelorism, deep-set eyes, short nose, small nares, prognathism, anteverted ears, sparse/thick hair, low posterior hairline, and distal finger/toe abnormalities. Mild microcephaly in two patients. Early-onset seizures in two patients.", "JOUBERT SYNDROME 6, Joubert syndrome": "Clinical features of this rare genetic disorder, known as Joubert syndrome, include agenesis of the vermis of the cerebellum, tremor, hypotonia, Dandy-Walker malformation, hypoplasia of the corpus callosum, occipital meningoencephalocele, coloboma of the optic nerve, cardiac malformations, cutaneous dimples, telecanthus, micrognathia, chorioretinal coloboma, large head, prominent forehead, high rounded eyebrows, epicanthal folds, ptosis, upturned nose, open mouth, low-set and tilted ears, oculomotor apraxia, hyperpnea, malformation of brainstem structures, temperament problems, hyperactivity, aggressiveness, dependency, severe cognitive and developmental impairment, absence of decussation of the superior cerebellar peduncles, dysmorphic facial features, genetic heterogeneity, liver fibrosis, coloboma, and retinal disease.", "BARAITSER-WINTER SYNDROME 2": "Baraitser-Winter syndrome-2: Short stature, postnatal microcephaly, intellectual disability, hearing loss, seizures, trigonocephaly, hypertelorism, high-arched eyebrows, ptosis, iris or retinal coloboma, lissencephaly.\n\nBaraitser-Winter syndrome, Fryns-Aftimos syndrome, cerebrofrontofacial syndrome: Dysmorphic facial features, hypertelorism, broad nose, non-myopathic ptosis, ridged metopic sutures, arched eyebrows, iris or retinal coloboma, sensorineural deafness, cleft lip and palate, hallux duplex, congenital heart defects, renal tract anomalies, microcephaly, pachygyria, lissencephaly, joint stiffness, intellectual disability, epilepsy.", "DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 18": "Clinical features of the rare genetic disorder include early-onset epileptic encephalopathy, severely delayed psychomotor development, hypotonia, lack of speech, and inability to sit or stand unsupported. Common facial dysmorphic features include high forehead, downslanting palpebral fissures, ptosis, and arched, laterally extended eyebrows. Brain MRI findings include short and thick corpus callosum, persistent cavum septum pellucidum, and sometimes hippocampal atrophy. Other features may include macrocephaly, autistic features, sandal gap between toes, and behavioral disturbances.", "NESTOR-GUILLERMO PROGERIA SYNDROME": "Rare genetic disorder: Nestor-Guillermo progeria syndrome (NGPS)\nPhenotype characteristics:\n- Atypical progeria with failure to thrive, dry skin, and light-brown spots\n- Generalized lipoatrophy, severe osteoporosis, and marked osteolysis\n- Pseudosenile facial appearance with micrognathia, subcutaneous venous patterning, convex nasal ridge, and proptosis\n- Normal cognitive development\n- Unique features: age, height (underestimated due to severe scoliosis), presence of eyebrows and eyelashes, persistence of scalp hair, severe osteolysis involving mandible, clavicles, ribs, distal phalanges, and radius, absence of coronary dysfunction, atherosclerosis, or metabolic anomalies\n- No signs of ischemia, atherosclerosis, insulin resistance, diabetes mellitus, or hypertriglyceridemia\n- Secondary pulmonary hypertension, severe scoliosis, restrictive spirometry pattern in some cases\n- Normal blood pressure, low 25-OH-vitamin D, very low leptin, low fasting glucose\n- Slow clinical course and relatively long survival despite early onset of disease.", "FACIAL DYSMORPHISM, LENS DISLOCATION, ANTERIOR SEGMENT ABNORMALITIES, AND SPONTANEOUS FILTERING BLEBS": "Clinical features of this rare genetic disorder include craniofacial dysmorphism (downward slanting palpebral fissures, large beaked nose, triangular retracted chin, dental malocclusion), ectopia lentis, angle closure, iridocorneal adhesions, atrophy in irides, avascular elevations of bulbar conjunctiva, normal body proportions, normal joint mobility, loss of vision, corneal opacification, retrocorneal nodular thickening, iridocorneal touch, flat anterior chamber, decreased axial lengths, retrocorneal fibrosis, beaked nose, flat cheeks, retrognathia, intraocular lens dislocation, spherophakia, filtering blebs, patchy iris atrophy, developmental delay, inguinal hernias, dolichocephaly, malar hypoplasia, high nasal ridge, high-arched palate, bifid uvula, irregularly placed teeth, small chin, pectus excavatum, cubiti valgi, long and thin fingers, joint hypermobility, and ocular abnormalities. Facial features may be subtle in some cases.", "SMG8": "Patients with this rare genetic disorder exhibit global developmental delay, impaired intellectual development, and poor or absent speech. They often have behavioral abnormalities such as autism and hyperactivity. Other features include hypotonia, unsteady gait, limb hypertonia, lower limb spasticity, and skin hyperpigmentation. Poor overall growth, short stature, and microcephaly are common, along with dysmorphic facial features like hypertelorism, strabismus, and low-set posteriorly-rotated ears. Congenital cardiac anomalies, including septal defects and abnormal positioning of the great arteries, are observed in some patients. Brain imaging may show cerebral atrophy or white matter abnormalities. Additional features can include hypospadias, early-onset cataracts, sensorineural hearing loss, and pigmentary retinopathy associated with Usher syndrome.", "COFFIN-SIRIS SYNDROME 4, Coffin-Siris syndrome": "Clinical features of the rare genetic disorder include mental retardation, absent or hypoplastic fifth fingernails/toenails, dysmorphic facial features (such as low anterior hairline, thick eyebrows, broad nose, thick lips), hypertrichosis, rough skin with hyperkeratotic plaques, short stature, myopia, strabismus, coarse facies, mild nail hypoplasia, behavioral abnormalities (obsessive-compulsive disorder, withdrawal, stubbornness, autistic features), hoarse or high-pitched voice, ventricular septal defect, patent ductus arteriosus, coarctation of the aorta, hip dislocation, muscular hypotonia, expressive speech delay, abnormal head shape, low-set and abnormally shaped ears, downslanting palpebral fissures, bulbous nasal tip, thin upper lip, minor teeth anomalies, brachydactyly or single palmar creases, hirsutism, frequent infections, absent/hypoplastic corpus callosum, intellectual disability, severe speech delay, agenesis of corpus callosum, microcephaly, seizures, Dandy-Walker malformation, vision and hearing problems, and sparse scalp hair.", "ANTLEY-BIXLER SYNDROME WITH GENITAL ANOMALIES AND DISORDERED STEROIDOGENESIS": "Phenotypic characteristics of the rare genetic disorder include genital anomalies, disordered pattern of steroidogenesis, and a lack of distinguishing dysmorphic features. Females with the disorder may exhibit abnormalities in steroid biogenesis. ABS with disordered steroidogenesis may be a distinct genetic entity.", "OROFACIODIGITAL SYNDROME I, Orofaciodigital syndrome": "Clinical features of the rare genetic disorder, orofaciodigital syndrome (OFD), include abnormal oral frenula, alveolar and lingual clefting, asymmetry of the cranial vault, nasal fossae, and mandible, cleft lip/palate, digital malformations, familial tremor, mental retardation, granular appearance of facial skin with diffuse alopecia and dry hair, polycystic kidneys, renal failure, agenesis of the corpus callosum, irregular mineralization of bones, central nervous system malformations, duplication of halluces, atrioventricular septal defect, variability in cleft palate and midline cleft of the upper lip, and phenotypic similarities with ciliopathies. OFD has multiple clinical subtypes and high clinical and genetic heterogeneity.", "GAND SYNDROME": "Rare genetic disorder phenotype characteristics: global developmental delay, delayed motor milestones, limited speech, severe intellectual disability, strabismus, facial dysmorphism (thin blonde hair, deeply set eyes, tubular nose, large mouth with thin upper lip), hypoplasia of optic nerve, tics, high pain threshold, hyperactivity, inappropriate laughter, obsession for shiny objects, self-mutilation, hypotonia, macrocephaly, poor coordination, seizures, frontal bossing, hypertelorism, high-arched palate, delayed language, impaired cognitive function, unsteady gait, expressive language difficulties, nonverbal, abnormal brain imaging, gastroesophageal reflux disease, oromotor dysfunction, cardiac abnormalities, behavioral problems, hand or feet anomalies, visual deficits, and rare seizures, cardiac defects, and pyramidal signs.", "MYHRE SYNDROME": "Clinical features of Myhre syndrome include mental retardation, pre- and postnatal growth deficiency, unusual facies (maxillary hypoplasia, prognathism, short palpebral fissures, short philtrum, small mouth), generalized muscle hypertrophy, decreased joint mobility, cryptorchidism, cardiac anomaly, early-onset deafness, osseous peculiarities (thickened calvaria, broad ribs, hypoplastic iliac wings, shortened long and tubular bones, large flattened vertebrae), short stature, limited joint mobility, thickened skin, and various cardiac and pulmonary pathologies. Paternal age may be a contributing factor.", "ZNF407": "Text 1: Two Arab brothers with a mutation in the ZNF407 gene had global developmental delay, impaired intellectual development, delayed speech, and shared dysmorphic features including midface hypoplasia, synophrys, ptosis, epicanthal folds, strabismus, prominent ears, downturned corners of the mouth, and thin vermilion of the upper lip. They also had kyphosis, thumb abnormalities, toe abnormalities, persistent fetal pads, hypotonia, and exaggerated deep tendon reflexes. Brain MRIs were normal.\n\nText 2: A consanguineous Pakistani family, a Brazilian girl, and a Filipino boy with mutations in ZNF407 had neurodevelopmental disorders. All affected individuals had impaired intellectual development, reduced motor and cognitive skills, short stature, and most had microcephaly. Other features included hypotonia, dysarthria, deafness, visual problems, enuresis, encopresis, behavioral anomalies, delayed pubertal onset, and facial dysmorphism.", "THREE M SYNDROME 1, Three M syndrome": "Clinical features of the rare genetic disorder include low birth weight dwarfism, narrow facies, grooved lower anterior thorax, clinodactyly, tall vertebral bodies, and normal intelligence. Other characteristics include normocephaly, short stature, malar hypoplasia, narrowed nasal body, full lips, overtubulation of long bones, short tubular bones of the hands and feet, and ligamentous laxity. The disorder is often seen in offspring of consanguineous parents and may be misdiagnosed as another growth retardation syndrome.", "PERCHING SYNDROME": "Text 1: Crisponi-like syndrome with hyperthermia, oropharyngeal muscle contractions, feeding difficulties, camptodactyly, joint contractures, full cheeks, high-arched palate, depressed nasal bridge. Some patients develop retinitis pigmentosa. No cold-induced sweating.\n\nText 2: PERCHING syndrome with intrauterine growth retardation, respiratory and feeding difficulties, dysmorphic features (microcephaly, hypertelorism, exophthalmos, etc.), contractures, recurrent infections, seizures, cardiac/genitourinary anomalies. No cold-induced sweating or hyperthermia.\n\nText 5: PERCHING syndrome with feeding problems, recurrent fevers, cold-induced sweating, global developmental delay, dysmorphic features (triangular face, sparse hair, etc.), failure to thrive, spasticity, contractures, nodular heterotopia, pigmentary changes in the retina. Similar to Bohring-Opitz syndrome. Only confirmed report of cold-induced sweating in KLHL7 mutations.\n\nText 4: PERCHING syndrome with IUGR, microcephaly, dysmorphic features, hypotonia, severe swallowing difficulties, impaired global development, abnormal posturing, sleep disturbances, recurrent infections, respiratory difficulties. No seizures or cold-induced sweating.", "WOLF-HIRSCHHORN SYNDROME": "The rare genetic disorder, Wolf-Hirschhorn syndrome, is characterized by severe growth retardation, microcephaly, distinctive facial features, and closure defects such as cleft lip or palate, coloboma of the eye, and cardiac septal defects. Other clinical features include mental retardation, optic atrophy, hearing loss, epilepsy, and skeletal abnormalities. Patients may also have heart lesions, orofacial clefts, and a seizure disorder. The prognosis varies depending on the severity of symptoms, and the mortality rate is lower than previously reported. Seizures tend to cease in childhood, and they may be triggered by fever. Neuroimaging findings often include abnormalities in the corpus callosum, white matter, and ventricles.", "MENTAL RETARDATION-HYPOTONIC FACIES SYNDROME, X-LINKED, 1": "Clinical features of the rare genetic disorder include mental retardation, microcephaly, short stature, unusual facial appearance (slanted palpebral fissures, narrow face, maxillary overjet, exotropia, ptosis), hypotonia, hyperreflexia, patulous lower lip, prominent upper central incisors, asplenia, bilateral cryptorchidism, cortical atrophy, dolichocephaly, cleft palate, micrognathia, Sidney line, minor foot deformities, walking instability, hyperactivity, severe delay in language development, deafness, genital abnormalities (small penis, hypospadias, cryptorchidism), epicanthal folds, short nose, equinovarus deformity, renal hypoplasia, bitemporal narrowness, almond-shaped palpebral fissures, depressed nasal bridge, anteverted nares, short and inverted-V-shaped upper lip, macrostomia, low total finger ridge count, bushy eyebrows, widely-spaced teeth, brachydactyly. The disorder may be inherited in an autosomal recessive or X-linked manner.", "COHEN SYNDROME": "Cohen syndrome is a rare autosomal recessive disorder characterized by psychomotor retardation, motor clumsiness, microcephaly, characteristic facial features, hypotonia, joint laxity, retinochoroidal dystrophy, myopia, intermittent neutropenia, and a cheerful disposition. The phenotype is highly homogeneous in Finnish patients but shows phenotypic variability in non-Finnish patients. Other features include obesity, hypotonia, high nasal bridge, prominent incisors, and mental deficiency. Additional findings may include chorioretinal dystrophy, granulocytopenia, laryngeal abnormalities, cardiac abnormalities, and cognitive impairments. The diagnosis is confirmed by molecular testing of the COH1 gene.", "INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISM AND SPEECH DELAY": "Rare genetic disorder: IDDAS\nPhenotype characteristics:\n- Autism spectrum disorder\n- Delayed intellectual development\n- Language delay\n- Verbal fluency varies\n- Nonverbal individuals\n- Cognitive functioning ranges from average to intellectually disabled\n- Joint hypermobility\n- Poor expressive language\n- Stereotypic behaviors\n- Impaired social interaction\n- Global developmental delay\n- Delayed walking and speech\n- Cortical migration defects on brain imaging\n- Hypotonia\n- Irregularity of cortical gray-white matter junction\n- Pachygyria and thick cortex\n- Thin corpus callosum (in one patient)\n- Inherited from unaffected parent in some cases\n- Sporadic occurrence in others\n- Unaffected parents in most cases", "SNIJDERS BLOK-CAMPEAU SYNDROME": "Clinical features of Snijders Blok-Campeau syndrome include global developmental delay, impaired intellectual development, autistic features, hypotonia, impaired speech and language development, macrocephaly, dysmorphic facial features, visual abnormalities, seizures, structural CNS abnormalities, congenital heart defects, and variable expressivity.", "GABRIELE-DE VRIES SYNDROME": "Neurodevelopmental disorder with delayed psychomotor development and intellectual disability. Variable phenotype: mild to severe cognitive impairment, speech delay, behavioral problems. Dysmorphic facial features: asymmetry, broad forehead, rotated ears, full nasal tip, thick lower lip. Feeding difficulties, skeletal abnormalities, abnormal movements. Additional features: craniosynostosis, extensible skin, lacrimal duct stenosis, esophageal atresia, hypothyroidism, tooth abnormalities, cryptorchidism. Abnormal brain imaging in some patients.", "MACS SYNDROME": "Clinical features of the rare genetic disorder include macrocephaly, downslanting palpebral fissures, puffy eyelids, mild ichthyosis, sagging cheeks, everted lower lip, retrognathia, gingival hyperplasia, abnormal teeth position, severe hyperlaxity, flat feet, coarse and swollen facial appearance, sparse scalp hair, scoliosis, short stature, aortic dilatation, osteoporosis, progressive facial coarsening, gingival hypertrophy, sparse hair, joint and skin laxity, mental retardation, bitemporal narrowing, cutis laxa, irregular teeth, thorax deformity, brachydactyly, soft sagging skin, hyperextensibility, bronchiectases, hypergonadotropic hypogonadism, sparse eyebrows, epicanthal folds, broad nasal bridge, umbilical hernia, easy bruising, and abnormal white matter signal on brain MRI.", "FAM20B": "The rare genetic disorder is associated with mutations in the FAM20B gene. The FAM20B gene is highly conserved in humans, mice, and rats. The protein encoded by FAM20B contains 459 amino acids and has a conserved signal sequence and C-terminal sequence. FAM20B, along with FAM20A and FAM20C, is expressed during hematopoiesis.", "MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 3": "Clinical features of the rare genetic disorder (MCAHS3) include severe intellectual and motor disability, multiple congenital anomalies, hypotonia, delayed psychomotor development, dysmorphic features (brachycephaly, high forehead, depressed nasal bridge, long philtrum, open mouth), brain abnormalities (frontotemporal atrophy, cerebellar hypoplasia), seizures, ophthalmologic findings (poor vision, strabismus, nystagmus), tooth abnormalities, renal abnormalities, skeletal findings (scoliosis, pectus excavatum, short upper extremities, slender and osteopenic long bones), inverted nipples, restrictive cardiomyopathy, and decreased alkaline phosphatase. Other features may include endocrine, hearing, and cardiac anomalies.", "PAGANINI-MIOZZO SYNDROME": "Syndromic neurodevelopmental disorder in Italian twin brothers: delayed psychomotor development, high myopia (-6 diopters), chorioretinopathy, febrile seizures (resolved), mildly enlarged lateral ventricles. Dysmorphic features: triangular face, large forehead, deep-set eyes, downslanting palpebral fissures and eyebrows, thin lips, downturned corners of the mouth, slight prognathism, pointed chin, small low-set malrotated ears. At age 10: feeding difficulties, urinary incontinence. Laboratory findings: mildly increased serum lactate, low glycemic scores.", "SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 13": "Spinocerebellar ataxia: infantile onset of delayed psychomotor development, gait and stance ataxia, dysarthria, dysmetria, tremor, dysdiadochokinesia, ophthalmologic abnormalities, short stature, pes planus, hypotonia, cerebellar atrophy, ventricular enlargement, retrocerebellar cysts, seizures, intellectual impairment, aggressive behavior, nystagmus, increased number of cerebellar cisterns, dystonic and choreiform movements.", "NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY AND STRUCTURAL BRAIN ANOMALIES": "Patients with this rare genetic disorder exhibit delayed psychomotor development, severe intellectual disability, microcephaly, short stature, and facial dysmorphisms including upslanting palpebral features, anteverted nares, and a bulbous nose. They also have dysarthric speech, behavioral abnormalities, and in some cases, spasticity, profound microcephaly, hypotonia, and hyperreflexia. Brain imaging reveals agenesis of the corpus callosum, cerebral cortical and brainstem hypoplasia, white matter hypoplasia, and gyral simplification.", "OCULOSKELETODENTAL SYNDROME": "Oculoskeletodental syndrome is characterized by dysmorphic facial features (coarse facies, low hairline, epicanthal folds, etc.), congenital cataract, hearing loss, dental anomalies, skeletal abnormalities, hypercalcemia with nephrocalcinosis, developmental delay, stroke, and elevated urinary mucopolysaccharide levels.", "EHLERS-DANLOS SYNDROME, SPONDYLODYSPLASTIC TYPE, 1": "Clinical features of the rare genetic disorder include severe short stature, generalized muscular hypotonia, ligamentous laxity with joint dislocations, hyperextensible and prone to infection skin, dysmorphic facial features, dental abnormalities, pectus carinatum, cardiovascular malformations, osteoporosis, delayed verbal development, and an aged appearance. Some patients also exhibit mental retardation, progeroid facies, joint hypermobility, and fragility of skin. The disorder is distinct from Larsen syndrome and Ehlers-Danlos syndrome, but shares some similarities. The phenotype may be influenced by modifier genes in the isolated population of Reunion Island.", "CORNELIA DE LANGE SYNDROME 3 WITH OR WITHOUT MIDLINE BRAIN DEFECTS": "pre- and postnatal growth failure, delayed psychomotor development and impaired intellectual development, hypertrichosis, and sometimes distal limb malformations  arched eyebrows, synophrys, and long eyelashes, thin lips, small hands and feet, proximally set thumbs, fifth finger clinodactyly, restriction of elbow movements, and hirsutism, in addition to high nasal bridge and high palate lacked brachycephaly, low anterior hairline, anteverted nostrils, long philtrum, downturned corners of the mouth, micrognathia, and hearing loss", "RUBINSTEIN-TAYBI SYNDROME 1": "mental retardation, postnatal growth deficiency, microcephaly, broad thumbs and halluces, and dysmorphic facial features. The facial appearance is striking, with highly arched eyebrows, long eyelashes, downslanting palpebral fissures, broad nasal bridge, beaked nose with the nasal septum, highly arched palate, mild micrognathia, and characteristic grimacing or abnormal smile", "AURICULOCONDYLAR SYNDROME 3, Auriculocondylar syndrome": "micrognathia, temporomandibular joint and condyle anomalies, microstomia, prominent cheeks, and question mark ears sleep apnea with snoring, conductive hearing loss, and trigger thumbs", "Tuberous sclerosis": "hamartomas in multiple organ systems, including the brain, skin, heart, kidneys, and lung. Central nervous system manifestations include epilepsy, learning difficulties, behavioral problems, and autism. Renal lesions, usually angiomyolipomas, can cause clinical problems secondary to hemorrhage or by compression and replacement of healthy renal tissue, which can cause renal failure. Patients can also develop renal cysts and renal-cell carcinomas. Pulmonary lymphangioleiomyomatosis can develop in the lungs. Skin lesions include melanotic macules, facial angiofibromas, and patches of connective tissue nevi", "DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 13": "seizures mild developmental delay impaired development or developmental regression after the onset of seizures, and show severe intellectual disability, poor or absent language, hypotonia, and are usually unable to walk. EEG shows variable abnormalities, including multifocal and generalized spike-wave discharges status epilepticus hypsarrhythmia cerebral atrophy", "FRANK-TER HAAR SYNDROME": "brachycephaly, wide fontanels, prominent forehead, hypertelorism, prominent eyes, macrocornea with or without glaucoma, fullcheeks, small chin, bowing of the long bones, and flexion deformity of the fingers. Protruding, simple ears and prominent coccyx", "HEART AND BRAIN MALFORMATION SYNDROME": "profoundly delayed psychomotor development, dysmorphic facial features, microphthalmia, cardiac malformations, mainly septal defects, and brainmalformations, including Dandy-Walker malformation", "MULTIPLE PTERYGIUM SYNDROME, ESCOBAR VARIANT": "short stature pterygia of the neck, axilla, and antecubital, popliteal, digital, and intercrural areas; multiplejoint contractures with crouched stance and cleft palate. Males had small penis and scrotum and cryptorchidism; females had aplasia of the labia majora and small clitoris. Skeletal anomalies included fusion of cervical vertebrae, scoliosis, flexion contraction of fingers, and rocker-bottom feet with vertical talus", "LISSENCEPHALY 3": "short stature pterygia of the neck, axilla, and antecubital, popliteal, digital, and intercrural areas; multiplejoint contractures with crouched stance and cleft palate. Males had small penis and scrotum and cryptorchidism; females had aplasia of the labia majora and small clitoris. Skeletal anomalies included fusion of cervical vertebrae, scoliosis, flexion contraction of fingers, and rocker-bottom feet with vertical talus", "FANCONI ANEMIA, COMPLEMENTATION GROUP S": "developmental delay apparent from infancy, short stature, microcephaly, and coarse dysmorphic features. Laboratory studies show defective DNA repair and increased chromosomal breakage during stress. Some patients may have radial ray anomalies, anemia, and increased risk of cancer; patients often have a family history of cancer in family members who have heterozygous mutations", "SHORT STATURE, BRACHYDACTYLY, IMPAIRED INTELLECTUAL DEVELOPMENT, AND SEIZURES": "Developmental Delays Physical Stature and Obesity Skeletal Abnormalities Endocrine Anomalies Seizures and Hypotonia Variable Dysmorphic Features", "MANDIBULOACRAL DYSPLASIA WITH TYPE A LIPODYSTROPHY": "growth retardation, craniofacial anomalies with mandibular hypoplasia, skeletal abnormalities with progressive osteolysis of the distal phalanges and clavicles, and pigmentary skin changes", "NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA, STEREOTYPIC HAND MOVEMENTS, AND IMPAIRED LANGUAGE": "global developmental delay with hypotonia, poor motor development with limited walking, impaired intellectual development with poor or absent speech, and behavioral abnormalities. Almost all affected individuals demonstrate repetitive stereotypichand movements that can be categorized as hyperkinetic and resembling those of Rett syndrome", "PHELAN-MCDERMID SYNDROME": "neonatal hypotonia, global developmental delay, normal to accelerated growth, absent to severely delayed speech, autistic behavior partial absence of corpus callosum, bilateral ureteropelvic structure, gastroesophageal reflux, and hearing loss", "ALPHA-THALASSEMIA/MENTAL RETARDATION SYNDROME, X-LINKED": "severe mental handicap, characteristic dysmorphic facies, genital abnormalities, and an unusual, mild form of hemoglobin H disease. Facial features included microcephaly, hypertelorism, epicanthus, a small triangular upturned nose, and flat face", "NEUROFIBROMATOSIS, TYPE I": "cafe-au-lait spots, Lisch nodules in the eye, and fibromatous tumors of the skin. Individuals with the disorder have increased susceptibility to the development of benign and malignant tumors", "INTELLECTUAL DEVELOPMENTAL DISORDER WITH BEHAVIORAL ABNORMALITIES AND CRANIOFACIAL DYSMORPHISM WITH OR WITHOUT SEIZURES": "impaired intellectual development or developmental delay of varying severity with impaired motor skills and language delay. Macrocephaly obesity overgrowth seizures autism", "Warburg micro syndrome": "microcephaly, microphthalmia, microcornea, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe mental retardation, spastic diplegia, and hypogonadism", "PETTIGREW SYNDROME": "impaired intellectual development  choreoathetosis, hydrocephalus, Dandy-Walker malformation, seizures, and iron or calcium deposition in the brain, both between and within families", "VAN DEN ENDE-GUPTA SYNDROME": "severecontractual arachnodactyly from birth and distinctive facial dysmorphism, including triangular face, malar hypoplasia, narrow nose, everted lips, and blepharophimosis. Skeletal anomalies includeslender ribs, hooked clavicles, and dislocated radial head", "NEU-LAXOVA SYNDROME 1, Neu-Laxova syndrome": "ichthyosis, marked intrauterine growth restriction, microcephaly, short neck, central nervous system anomalies lissencephaly, cerebellar hypoplasia a abnormal/agenesisof the corpus callosum, limb deformities, hypoplastic lungs, edema, and abnormal facial featuresincluding severe proptosis with ectropion, hypertelorism, micrognathia, flattened nose, andmalformed ears", "PRADER-WILLI SYNDROME": "diminished fetal activity, obesity, muscular hypotonia, mental retardation, short stature, hypogonadotropic hypogonadism, and small hands and feet", "MENTAL RETARDATION, AUTOSOMAL RECESSIVE 53": "nonsyndromic impaired intellectual development mild motor delay moderate intellectual disability, and single word speech early-onset epilepsy", "ATP9A": "global developmental delay, moderately to severely impaired intellectual development, often with absent speech, and behavioral abnormalities, including hyperactivity, short attention span, and ADHD. failure to thrive with poor overall growth microcephaly nonspecific facial dysmorphism, hypotonia, and feeding difficulties", "PHIP": "straight eyebrows, strabismus, blepharophimosis, ptosis, a long philtrum and full lips, tapered fingers, clinodactyly of fifth fingers, and long toes impaired intellectual development or learning difficulties, behavioral abnormalities obesity", "NAA15, TPO, CITED2": "Intellectual development, delayed speech and motor milestones, and behavioral abnormalities, most commonly autism spectrum disorder(ASD). Some patients may also have mild craniofacial dysmorphism, congenital cardiac anomalies, or seizures", "CSNK2B": "early-onset seizures and variably impaired intellectual development (ID). The severity of neurologic impairment is highly variable: some patients may have refractory seizures and be bedridden with no meaningful speech, whereas others may have treatment-responsive seizures and achieve normal psychomotor development", "FRASER SYNDROME 2": "cryptophthalmos, nasal dysplasia with hypoplastic alae nasi, multiple skin syndactyly in all extremities, and short thorax with abdominal distention", "MUCOPOLYSACCHARIDOSIS, TYPE IVA": "short stature, skeletal dysplasia, dental anomalies, and corneal clouding intracellular accumulation of keratan sulfate and chondroitin-6-sulfate", "SOTOS SYNDROME 1": "Abnormality of the cardiovascular system Flushing Broad forehead Seizure Dolichocephaly Autistic behavior Downslanted palpebral fissures Global developmental delay Scoliosis Long face Ventriculomegaly Abnormality of the kidney Accelerated skeletal maturation Abnormal mandible morphology Sparse anterior scalp hair Soft, doughy skin Overgrowth", "CARDIOFACIOCUTANEOUS SYNDROME 1": "high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices pulmonic stenosis, atrial septal defect, and hypertrophic cardiomyopathy sparse and friable hair, hyperkeratotic skin lesions", "MENTAL RETARDATION, AUTOSOMAL DOMINANT 26": "ptosis, prominent nasal tip, deep nasal bridge, and short or upturned philtrum intellectual disability, an autism spectrum disorder, feeding difficulties after birth, mild distal joint contractures", "Opitz GBBB syndrome": "hypertelorism, hypospadias, cleft lip/palate, laryngotracheoesophageal abnormalities, imperforate anus, developmental delay, and cardiac defects", "Seckel syndrome": "intrauterine growth retardation, dwarfism, microcephaly with mental retardation, and a characteristic bird-headed facial appearance", "DEVELOPMENTAL DELAY WITH OR WITHOUT INTELLECTUAL IMPAIRMENT OR BEHAVIORAL ABNORMALITIES": "neonatal feeding problems, hypotonia, and dysmorphic facial features", "Mandibuloacral dysplasia with lipodystrophy": "growth retardation, craniofacial anomalies with mandibular hypoplasia, skeletal abnormalities with progressive osteolysis of the distal phalanges and clavicles, and pigmentary skin changes marked acral loss of fatty tissue with normal or increased fatty tissue in the neck and trunk", "CHROMOSOME 1p36 DELETION SYNDROME": "deep-set eyes, flat nasal bridge, asymmetric ears, and pointed chin seizures, cardiomyopathy, developmental delay, and hearing impairment  short stature prominent forehead brachycephaly microcephaly midface hypoplasia prominent jaw/chin dysplastic pinna hearing loss congenital heart disease hypotonia facial clefting early demise", "NEURODEVELOPMENTAL DISORDER WITH OR WITHOUT HYPERKINETIC MOVEMENTS AND SEIZURES, AUTOSOMAL DOMINANT": "developmental delay, severe intellectual disability with absent speech, muscular hypotonia, and a hyperkinetic movement disorder cortical blindness, generalized cerebral atrophy, and seizures", "EPILEPSY, FOCAL, WITH SPEECH DISORDER AND WITH OR WITHOUT IMPAIRED INTELLECTUAL DEVELOPMENT": "profound developmental delay, severe intellectual disability with absent speech, muscular hypotonia, and a hyperkinetic movementdisorder. Additional features may include cortical blindness, generalized cerebral atrophy, and seizures", "MENTAL RETARDATION, AUTOSOMAL DOMINANT 6, WITH OR WITHOUT SEIZURES": "delayed psychomotor development and intellectual disability of variable severity seizures, hypotonia, abnormal movements dystonia autistic features", "DOWN SYNDROME": "delayed psychomotor development and intellectual disability of variable severity seizures, hypotonia, abnormal movements, such as dystonia, and autistic features", "GOMEZ-LOPEZ-HERNANDEZ SYNDROME; GLHS": "craniosynostosis, ataxia, trigeminal anesthesia, scalp alopecia, cerebellar anomaly, midface hypoplasia, corneal opacities, low-set ears, mental retardation, and short stature", "CUL7": "severe prenatal and postnatal growth retardation, and normal mental development. The main skeletal anomalies are long, slender tubular bones, reduced anteroposterior diameter of the vertebral bodies, and delayed bone age. Other skeletal manifestations include joint hypermobility, joint dislocation, winged scapulae, and pes planus", "OBSL1": "low birth weight and short stature, relative macrocephaly, lumbar hyperlordosis, and prominent heels triangular face with frontal bossing and midface hypoplasia, anteverted nares with fleshy nasal tip, and full fleshy lips", "ECEL1": "adducted thumbs and wrists; mild camptodactyly of the toes; clubfoot and/or a calcaneovalgus deformity; extension contractures of the knee; unilateral ptosis or ptosis that is more severe on one side; a round-shaped face; arched eyebrows; a bulbous, upturned nose; and micrognathia. Notably, these patients do not have ophthalmoplegia", "LRP2": "prominent brow, short nose, and hypertelorism, and ocular anomalies include myopia, iris hypoplasia retinal detachment ocular anomalies, sensorineural hearing loss, and proteinuria", "ASNS": "microcephaly, severely delayed psychomotor development, progressive encephalopathy, cortical atrophy, and seizure hyperekplexic activity", "ASPM": "mental retardation and speech delay short stature mild seizures mild motor delay simplified gyral pattern enlarged ventricles partial agenesis of the corpus callosum mild cerebellar hypoplasia focal cortical dysplasia unilateral polymicrogyria", "CDK8": "Neurodevelopmental Disorder, Hypotonia Global Developmental Delay Learning Disabilities Behavioral Abnormalities Variable Additional Features Facial Dysmorphia Congenital Heart Defects Visual or Ocular Movement Anomalies Feeding Difficulties and Gastroesophageal Reflux", "BBS7": "retinitis pigmentosa, postaxial polydactyly, mental retardation, obesity, renal anomalies hypogenitalism", "KCTD7": "Early-Onset Progressive Myoclonic Epilepsy Myoclonic Seizures Neurodegeneration and Regression Cognitive and Motor Impairments Permanent Myoclonus Transient Neurological Improvement Normal Ultrastructural Analysis of Skin Biopsy", "DYRK1A": "bitemporal narrowing deep-set eyes large simple ears a pointed nasal tip failure to thrive abnormal movements hypoactivity febrile seizures", "DPH1": "short stature broad forehead central nervous system malformations cardiac defects genital anomalies hypotonia", "KIF11": "upslanting palpebral fissures broad nose with rounded tip long philtrum with thin upper lip, prominent chin, and prominent ears. Chorioretinopathy is the most common eye abnormality, but retinal folds, microphthalmia, and myopic and hypermetropic astigmatism no overt ocular phenotype. Congenital lymphedema", "WAC": "broad forehead, depressed nasal bridge with bulbous nasal tip, and deep-set eyes gastrointestinal and mild ocular abnormalities", "TCIRG1": "macrocephaly, progressive deafness and blindness, hepatosplenomegaly, and severe anemia", "TCF20": "somatic overgrowth macrocephaly, obesity, and tall stature hypotonia, ataxic movements inverted nipples prominent forehead, downturned corners of the mouth, and prominent lower lip scoliosis sleep disturbances onset of seizures", "SUCLA2": "infantile-onset hypotonia, muscle atrophy, hyperkinesias, severe hearing impairment, postnatal growth retardation, and lactic acidosis scoliosis kyphosis, recurrent airway infections", "FRAS1": "cryptophthalmos, syndactyly, and abnormalities of the respiratory and urogenital tract", "WDR73": "severe global developmental delay, intellectual disability with lack of speech, mild microcephaly, axial hypotonia and inability to walk spastic quadriplegia with limited joint mobility and talipes foot deformities hypertelorism, epicanthal folds, large nose with prominent nasal bridge and tip, wide mouth, and strabismus", "PRMT7": "round head, short hairy forehead, hypoplasia of the supraorbital ridges, deep-set eyes, ptosis, infraorbital creases, flat nasal bridge with a broad nasal root and tip, anteverted nostrils, long philtrum, thin lips, high-arched palate, retrognathia, square chin, and short neck laryngomalacia necessitating G-tube placement, cryptorchidism, small feet, and brachydactyly", "AP4B1": "neonatal hypotonia that progresses to hypertonia and spasticity and severe mental retardation with poor or absent speech development", "VPS13B": "facial dysmorphism, microcephaly, truncal obesity, impaired intellectual development, progressive retinopathy, and intermittent congenital neutropenia", "RERE": "intrauterine or postnatal growth retardation, feeding difficulties, hypotonia, and behavioral problems. Four patients had variable ophthalmologic abnormalities, including microphthalmia, iris anomalies, coloboma, Peter anomaly, optic atrophy, cortical visual impairment, strabismus, and blepharophimosis", "MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 1": "autosomal recessive disorder characterized by neonatal hypotonia, lack of psychomotor development, seizures, dysmorphic features, and variable congenital anomalies involving the cardiac, urinary gastrointestinal systems", "ASPARAGINE SYNTHETASE DEFICIENCY": "microcephaly, severely delayed psychomotor development, progressive encephalopathy, cortical atrophy, and seizure or hyperekplexic activity", "MANNOSIDOSIS, ALPHA B, LYSOSOMAL": "mental retardation, coarse facial features, skeletal abnormalities, hearing impairment, neurologic motor problems, and immune deficiency", "Cardiofaciocutaneous syndrome, Noonan syndrome": "short stature broad forehead, hypertelorism, downslanting palpebral fissures, a high-arched palate, and low-set, posteriorly rotated ears", "MUCOPOLYSACCHARIDOSIS, TYPE II": "severe airway obstruction, skeletal deformities, cardiomyopathy, and, in most patients, neurologic decline", "MUCOPOLYSACCHARIDOSIS, TYPE IIIA": "severe central nervous system degeneration mild somatic disease severe neurologic degeneration", "GERODERMA OSTEODYSPLASTICUM": "skin wrinkling limited to the dorsa of hands and feet and to the abdomen, bowed long bones, and osteopenia with frequent fractures. There is a distinctive facial appearance with droopy skin at the cheeks, maxillary hypoplasia, and large ears. Adult patients appear prematurely aged", "Kleefstra syndrome": "severe mental retardation, hypotonia, brachy(micro)cephaly, epileptic seizures, flat face with hypertelorism, synophrys, anteverted nares, everted lower lip, carp mouth with macroglossia, and heart defects", "KDM2B": "developmental delay and/or intellectual disability, autism, attention deficit disorder/attention deficit hyperactivity disorder, congenital anomalies mainly affecting the heart, eyes, and urogenital system, and subtle facial dysmorphism", "CUTIS LAXA, AUTOSOMAL DOMINANT 1": "moderate subglottic stenosis with floppy airway structures, redundant mitral and tricuspid valves, mild dilatation of the proximal aorta and great vessels, and umbilical and inguinal hernias", "INTELLECTUAL DEVELOPMENTAL DISORDER WITH NASAL SPEECH, DYSMORPHIC FACIES, AND VARIABLE SKELETAL ANOMALIES": "mildly impaired global development, speech delay withnasal speech, and dysmorphic facial features, including high forehead, midface hypoplasia, micrognathia or high-arched palate, hypo/hypertelorism, upslanting palpebral fissures, and thin upper lip. Some patients may have skeletal anomalies, such as brachydactyly, 2-3 toe syndactyly, and flat feet", "SPASTIC PARAPLEGIA 50, AUTOSOMAL RECESSIVE": "neonatal hypotonia that progresses to hypertonia and spasticity and severely impaired intellectual development with poor or absent speech development"}