Hypertelorism, and Glioma

NEUROFIBROMATOSIS-NOONAN SYNDROME; NFNS Is also known as neurofibromatosis with noonan phenotype|noonan-neurofibromatosis syndrome

• Global developmental delay
• Short stature
• Scoliosis
• Hypertelorism
• Muscle weakness

SOURCES: ORPHANET OMIM MENDELIAN

17q11.2 microduplication syndrome is characterized by dysmorphic features and intellectual deficit.

17Q11.2 MICRODUPLICATION SYNDROME Is also known as trisomy 17q11.2|nf1 microdeletion syndrome|van asperen syndrome|grisart-destrÉe syndrome|dup(17)(q11.2)|neurofibromatosis 1 microdeletion syndrome

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

SOURCES: ORPHANET OMIM MENDELIAN

Neurofibromatosis type I is an autosomal dominant disorder characterized by 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. NF1 is sometimes referred to as 'peripheral neurofibromatosis.' The worldwide incidence of NF1 is 1 in 2,500 to 1 in 3,000 individuals (reviews by Shen et al., 1996 and Williams et al., 2009).Type II neurofibromatosis (NF2 ) is a genetically distinct disorder caused by mutation in the gene encoding merlin (NF2 ) on chromosome 22q12. NF2, sometimes known as 'central neurofibromatosis,' is characterized by bilateral acoustic neuroma and meningioma, but few skin lesions or neurofibromas (Rouleau et al., 1993).Some patients with homozygous or compound heterozygous mutations in mismatch repair genes (see, e.g., MLH1; {120436} and MSH2; {609309}) have a phenotype characterized by early onset malignancies and mild features of NF1, especially cafe-au-lait spots; this is known as the mismatch repair cancer syndrome (OMIM ), sometimes referred to as brain tumor-polyposis syndrome-1 or Turcot syndrome. These patients typically do not have germline mutations in the NF1 gene, although a study by Wang et al. (2003) suggested that biallelic mutations in mismatch repair genes may cause somatic mutations in the NF1 gene, perhaps resulting in isolated features resembling NF1.See also Legius syndrome (OMIM ), a genetically distinct disorder with a similar phenotype to NF1.

NEUROFIBROMATOSIS TYPE 1 DUE TO NF1 MUTATION OR INTRAGENIC DELETION Is also known as von recklinghausen disease due to nf1 mutation or intragenic deletion|neurofibromatosis, peripheral type|von recklinghausen disease

• Intellectual disability
• Seizures
• Short stature
• Scoliosis
• Hypertelorism

SOURCES: ORPHANET OMIM MENDELIAN

BASAL CELL NEVUS SYNDROME; BCNS Is also known as nevoid basal cell carcinoma syndrome|gorlin-goltz syndrome|gorlin syndrome|nbccs|multiple basal cell nevi, odontogenic keratocysts, and skeletal anomalies

• Intellectual disability
• Hearing impairment
• Microcephaly
• Scoliosis
• Ataxia

SOURCES: OMIM MENDELIAN

Cowden syndrome (CS) is a difficult to recognize, under-diagnosed genodermatosis characterized by the presence of multiple hamartomas in various tissues and an increased risk for malignancies of the breast, thyroid, endometrium, kidney and colorectum. When CS is accompanied by germline PTEN mutations, it belongs to the PTEN hamartoma tumor syndrome (PHTS; see this term) group.

COWDEN SYNDROME Is also known as bzs|cowden disease|bbrs|macrocephaly, multiple lipomas, and hemangiomata|pten hamartoma tumor syndrome with granular cell tumor|bannayan-zonana syndrome|macrocephaly, pseudopapilledema, and multiple hemangiomata|cs|cd|mham|pten hamartoma tumor syndrome|ri

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

SOURCES: ORPHANET OMIM MENDELIAN

Fanconi anemia (FA) is a clinically and genetically heterogeneous disorder that causes genomic instability. Characteristic clinical features include developmental abnormalities in major organ systems, early-onset bone marrow failure, and a high predisposition to cancer. The cellular hallmark of FA is hypersensitivity to DNA crosslinking agents and high frequency of chromosomal aberrations pointing to a defect in DNA repair (summary by Deakyne and Mazin, 2011).For additional general information and a discussion of genetic heterogeneity of Fanconi anemia, see {227650}.

• Microcephaly
• Growth delay
• Hypertelorism
• Neoplasm
• Failure to thrive

SOURCES: MESH OMIM MENDELIAN

Curry-Jones syndrome is a form of syndromic craniosynostosis characterized by unilateral coronal craniosynostosis or multiple suture synostosis associated with complete or partial agenesis of the corpus callosum, preaxial polysyndactyly and syndactyly of hands and/or feet, along with anomalies of the skin (characteristic pearly white areas that become scarred and atrophic, abnormal hair growth around the eyes and/or cheeks, and on the limbs), eyes (iris colobomas, microphthalmia,) and intestine (congenital short gut, malrotation, dysmotility, chronic constipation, bleeding and myofibromas). Developmental delay and variable degrees of intellectual disability may also be observed. Multiple intra-abdominal smooth muscle hamartomas, trichoblastoma of the skin, occipital meningoceles and development of desmoplastic medulloblastoma have been reported.

CURRY-JONES SYNDROME Is also known as corpus callosum agenesis-polysyndactyly syndrome|craniofacial malformations, asymmetric, with polysyndactyly and abnormal skin and gut development

• Intellectual disability
• Global developmental delay
• Microcephaly
• Hypertelorism
• Nystagmus

SOURCES: OMIM ORPHANET MESH MENDELIAN

Molybdenum cofactor deficiency (MOCOD) is a rare autosomal recessive metabolic disorder characterized by onset in infancy of poor feeding, intractable seizures, and severe psychomotor retardation. Characteristic biochemical abnormalities include decreased serum uric acid and increased urine sulfite levels due to the combined enzymatic deficiency of xanthine dehydrogenase (XDH ) and sulfite oxidase (SUOX ), both of which use molybdenum as a cofactor. Most affected individuals die in early childhood (summary by Reiss, 2000; Reiss et al., 2011). Genetic Heterogeneity of Molybdenum Cofactor DeficiencySee also MOCOD, complementation group B (MOCODB ), caused by mutation in the MOCS2 gene (OMIM ) on chromosome 5q11; and MOCOD, complementation group C (MOCODC ), caused by mutation in the GPHN gene (OMIM ) on chromosome 14q24.

SULFITE OXIDASE DEFICIENCY DUE TO MOLYBDENUM COFACTOR DEFICIENCY TYPE A Is also known as sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase, combined deficiency of|combined deficiency of sulfite oxidase, xanthine dehydrogenase and aldehyde oxidase type a|mocod type a

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

SOURCES: ORPHANET OMIM MESH MENDELIAN

Neurohypophyseal diabetes insipidus is an autosomal dominant disorder of free water conservation characterized by childhood onset of polyuria and polydipsia. Affected individuals are apparently normal at birth, but characteristically develop symptoms of vasopression deficiency during childhood (summary by Wahlstrom et al., 2004).

DIABETES INSIPIDUS, NEUROHYPOPHYSEAL Is also known as diabetes insipidus, cranial type|diabetes insipidus, primary central|cdi

• Intellectual disability
• Seizures
• Growth delay
• Hypertelorism
• Neoplasm

SOURCES: OMIM MENDELIAN

Molybdenum cofactor deficiency is a rare autosomal recessive metabolic disorder characterized by neonatal onset of intractable seizures, opisthotonus, and facial dysmorphism associated with hypouricemia and elevated urinary sulfite levels. Affected individuals show severe neurologic damage and often die in early childhood (summary by Reiss et al., 1999).For a general phenotypic description and a discussion of genetic heterogeneity of MOCOD, see MOCODA (OMIM ), which is clinically indistinguishable from MOCODB.

SULFITE OXIDASE DEFICIENCY DUE TO MOLYBDENUM COFACTOR DEFICIENCY TYPE B Is also known as combined deficiency of sulfite oxidase, xanthine dehydrogenase and aldehyde oxidase type b|mocod type b

• Seizures
• Global developmental delay
• Generalized hypotonia
• Microcephaly
• Growth delay

SOURCES: OMIM ORPHANET MESH MENDELIAN