Depressed nasal bridge, and Headache

Craniodiaphyseal dysplasia is a severe bone dysplasia characterized by massive generalized hyperostosis and sclerosis, especially involving the skull and facial bones. Progressive bony encroachment upon cranial foramina leads to severe neurologic impairment in childhood (summary by Brueton and Winter, 1990). The sclerosis is so severe that the resulting facial distortion is referred to as 'leontiasis ossea' (leonine facies), and the bone deposition results in progressive stenosis of craniofacial foramina (summary by Kim et al., 2011).

• Short stature
• Hearing impairment
• Hypertelorism
• Depressed nasal bridge
• Wide nasal bridge

SOURCES: OMIM MENDELIAN

JACKSON-WEISS SYNDROME; JWS Is also known as craniosynostosis, midfacial hypoplasia, and foot abnormalities

• Intellectual disability
• Hypertelorism
• Strabismus
• Cleft palate
• Ptosis

SOURCES: MESH OMIM MENDELIAN

Sclerosteosis is a very rare serious sclerosing hyperostosis syndrome characterized clinically by variable syndactyly and progressive skeletal overgrowth (particularly of the skull), resulting in distinctive facial features (mandibular overgrowth, frontal bossing, midfacial hypoplasia), cranial nerve entrapment causing facial palsy and deafness, and potentially lethal elevation of intracranial pressure.

SCLEROSTEOSIS Is also known as cortical hyperostosis-syndactyly syndrome|sost|cortical hyperostosis with syndactyly

• Hearing impairment
• Hypertelorism
• Nystagmus
• Strabismus
• Sensorineural hearing impairment

SOURCES: ORPHANET OMIM MENDELIAN

Ornithine transcarbamylase deficiency is an X-linked inborn error of metabolism of the urea cycle which causes hyperammonemia. The disorder is treatable with supplemental dietary arginine and low protein diet.Urea cycle disorders are characterized by the triad of hyperammonemia, encephalopathy, and respiratory alkalosis. Five disorders involving different defects in the biosynthesis of the enzymes of the urea cycle have been described: OTC deficiency, carbamyl phosphate synthetase deficiency (OMIM ), argininosuccinate synthetase deficiency, or citrullinemia (OMIM ), argininosuccinate lyase deficiency (OMIM ), and arginase deficiency (OMIM ).

ORNITHINE TRANSCARBAMYLASE DEFICIENCY, HYPERAMMONEMIA DUE TO Is also known as ornithine carbamoyltransferase deficiency|otc deficiency

• Intellectual disability
• Seizures
• Global developmental delay
• Ataxia
• Growth delay

SOURCES: ORPHANET OMIM MENDELIAN

Schimke immuno-osseous dysplasia (SIOD) is a multisystem disorder characterized by spondyloepiphyseal dysplasia and disproportionate short stature, facial dysmorphism, T-cell immunodeficiency, and glomerulonephritis with nephrotic syndrome.

SCHIMKE IMMUNO-OSSEOUS DYSPLASIA Is also known as immunoosseous dysplasia, schimke type|schimke syndrome|spondyloepiphyseal dysplasia-nephrotic syndrome

• Intellectual disability
• Seizures
• Short stature
• Scoliosis
• Growth delay

SOURCES: OMIM ORPHANET MESH MENDELIAN

Glutaric aciduria II (GA2) is an autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It differs from GA I (GA1 ) in that multiple acyl-CoA dehydrogenase deficiencies result in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids. GA II results from deficiency of any 1 of 3 molecules: the alpha (ETFA) and beta (ETFB) subunits of electron transfer flavoprotein, and electron transfer flavoprotein dehydrogenase (ETFDH). The clinical picture of GA II due to the different defects appears to be indistinguishable; each defect can lead to a range of mild or severe cases, depending presumably on the location and nature of the intragenic lesion, i.e., mutation, in each case (Goodman, 1993; Olsen et al., 2003).The heterogeneous clinical features of patients with MADD fall into 3 classes: a neonatal-onset form with congenital anomalies (type I), a neonatal-onset form without congenital anomalies (type II), and a late-onset form (type III). The neonatal-onset forms are usually fatal and are characterized by severe nonketotic hypoglycemia, metabolic acidosis, multisystem involvement, and excretion of large amounts of fatty acid- and amino acid-derived metabolites. Symptoms and age at presentation of late-onset MADD are highly variable and characterized by recurrent episodes of lethargy, vomiting, hypoglycemia, metabolic acidosis, and hepatomegaly often preceded by metabolic stress. Muscle involvement in the form of pain, weakness, and lipid storage myopathy also occurs. The organic aciduria in patients with the late-onset form of MADD is often intermittent and only evident during periods of illness or catabolic stress (summary by Frerman and Goodman, 2001).Importantly, riboflavin treatment has been shown to ameliorate the symptoms and metabolic profiles in many MADD patients, particularly those with type III, the late-onset and mildest form (Liang et al., 2009).

MULTIPLE ACYL-COA DEHYDROGENASE DEFICIENCY; MADD Is also known as ema|ethylmalonic-adipicaciduria|glutaric aciduria ii|ga ii|glutaric acidemia ii|ga2

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Ataxia

SOURCES: OMIM ORPHANET MENDELIAN

Saethre-Chotzen syndrome (SCS) is an inherited craniosynostosis syndrome characterized by unilateral or bilateral coronal synostosis, facial asymmetry, ptosis, strabismus and small ears with prominent crus, among other less common manifestations.

SAETHRE-CHOTZEN SYNDROME Is also known as acs3|acrocephalosyndactyly type 3|scs|acrocephaly, skull asymmetry, and mild syndactyly|acs iii|acrocephalosyndactyly, type iii|chotzen syndrome

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Hearing impairment

SOURCES: OMIM ORPHANET MENDELIAN

Noonan syndrome (NS) is an autosomal dominant disorder characterized by short stature, facial dysmorphism, and a wide spectrum of congenital heart defects. The distinctive facial features consist of a broad forehead, hypertelorism, downslanting palpebral fissures, a high-arched palate, and low-set, posteriorly rotated ears. Cardiac involvement is present in up to 90% of patients. Pulmonic stenosis and hypertrophic cardiomyopathy are the most common forms of cardiac disease, but a variety of other lesions are also observed. Additional relatively frequent features include multiple skeletal defects (chest and spine deformities), webbed neck, mental retardation, cryptorchidism, and bleeding diathesis (summary by Tartaglia et al., 2002). Genetic Heterogeneity of Noonan SyndromeSee also NS3 (OMIM ), caused by mutation in the KRAS gene (OMIM ); NS4 (OMIM ), caused by mutation in the SOS1 gene (OMIM ); NS5 (OMIM ), caused by mutation in the RAF1 gene (OMIM ); NS6 (OMIM ), caused by mutation in the NRAS gene (OMIM ); NS7 (OMIM ), caused by mutation in the BRAF gene (OMIM ); NS8 (OMIM ), caused by mutation in the RIT1 gene (OMIM ); NS9 (OMIM ), caused by mutation in the SOS2 gene (OMIM ); and NS10 (OMIM ), caused by mutation in the LZTR1 gene (OMIM ).See also NS2 (OMIM ) for a possible autosomal recessive form of NS; Noonan syndrome-like disorder with loose anagen hair-1 (NSLH1 ), caused by mutation in the SHOC2 gene (OMIM ); Noonan syndrome-like disorder with loose anagen hair-2 (NSLH2 ), caused by mutation in the PPP1CB gene (OMIM ); and Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL ), caused by mutation in the CBL gene (OMIM ).Mutations in the neurofibromin gene (NF1 ), which is the site of mutations causing classic neurofibromatosis type I (NF1 ), have been found in neurofibromatosis-Noonan syndrome (NFNS ).

NOONAN SYNDROME 1; NS1 Is also known as female pseudo-turner syndrome|male turner syndrome|noonan syndrome|turner phenotype with normal karyotype

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Microcephaly

SOURCES: OMIM MENDELIAN

Osteopathia striata with cranial sclerosis (OS-CS) is a bone dysplasia characterized by longitudinal striations of the metaphyses of the long bones, sclerosis of the craniofacial bones, macrocephaly, cleft palate and hearing loss.

OSTEOPATHIA STRIATA-CRANIAL SCLEROSIS SYNDROME Is also known as hyperostosis generalisata with striations|robinow-unger syndrome

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: ORPHANET MESH OMIM MENDELIAN

Proteus syndrome (PS) is a very rare and complex hamartomatous overgrowth disorder characterized by progressive overgrowth of the skeleton, skin, adipose, and central nervous systems.

PROTEUS SYNDROME Is also known as partial gigantism-nevi-hemihypertrophy-macrocephaly syndrome|gigantism, partial, of hands and feet, nevi, hemihypertrophy, and macrocephaly

• Intellectual disability
• Seizures
• Scoliosis
• Hypertelorism
• Nystagmus

SOURCES: ORPHANET OMIM MESH MENDELIAN