Intellectual disability, and Dilatation

DFNX2, also known as DFN3, is an X-linked recessive disorder characterized by progressive conductive and sensorineural hearing loss and a pathognomonic temporal bone deformity that includes dilatation of the inner auditory canal and a fistulous connection between the internal auditory canal and the cochlear basal turn, resulting in a perilymphatic fluid 'gusher' during stapes surgery (summary by de Kok et al., 1995 and Song et al., 2010).See also choroideremia, deafness, and mental retardation (OMIM ), a contiguous gene deletion syndrome involving the POU3F4 and CHM (OMIM ) genes on Xq21; isolated choroideremia (OMIM ) is caused by mutation in the CHM gene.

DEAFNESS, X-LINKED 2; DFNX2 Is also known as deafness 3, conductive, with stapes fixation|sensorineural deafness, profound, with or without a conductive component, associated with a unique developmental abnormality of the ear|perilymphatic gusher-deafness syndrome|deafness, mixed, with perilymphatic

• Intellectual disability
• Global developmental delay
• Hearing impairment
• Sensorineural hearing impairment
• Edema

SOURCES: OMIM MENDELIAN

Chudley-McCullough syndrome is a rare, genetic, syndromic deafness characterized by severe to profound, bilateral, sensorineural hearing loss (congenital or rapidly progressive in infancy) associated with a complex brain malformation including hydrocephalus, varying degrees of partial corpus callosum agenesis, colpocephaly, cerebral and cerebellar cortical dysplasia (bilateral medial frontal polymicrogyria, bilateral frontal subcortical heteropia) and, in some, arachnoid cysts. Major physical abnormalities or psychomotor delay are usually not associated.

CHUDLEY-MCCULLOUGH SYNDROME Is also known as dfnb82, formerly|deafness, sensorineural, with partial agenesis of the corpus callosum and arachnoid cysts|deafness, autosomal recessive 82, formerly

• Intellectual disability
• Seizures
• Global developmental delay
• Hearing impairment
• Sensorineural hearing impairment

SOURCES: ORPHANET OMIM MESH MENDELIAN

MDDGB3 is an autosomal recessive congenital muscular dystrophy with mental retardation and mild brain abnormalities (Clement et al., 2008). It is part of a group of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1 ), collectively known as 'dystroglycanopathies' (Mercuri et al., 2009).For a discussion of genetic heterogeneity of congenital muscular dystrophy-dystroglycanopathy type B, see MDDGB1 (OMIM ).

MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH MENTAL RETARDATION), TYPE B, 3; MDDGB3 Is also known as muscular dystrophy, congenital, pomgnt1-related

• Intellectual disability
• Microcephaly
• Strabismus
• Motor delay
• Myopia

SOURCES: OMIM MENDELIAN

Lissencephaly-4 is an autosomal recessive neurodevelopmental disorder characterized by lissencephaly, severe brain atrophy, extreme microcephaly (head circumference of more than 10 standard deviations (SD) below the mean), and profound mental retardation. It has also been referred to as 'microlissencephaly' (summary by Bakircioglu et al., 2011 and Alkuraya et al., 2011).For a general phenotypic description and a discussion of genetic heterogeneity of lissencephaly, see LIS1 (OMIM ).

LISSENCEPHALY 4; LIS4 Is also known as lissencephaly 4 with microcephaly

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

SOURCES: OMIM MENDELIAN

Brunelli et al. (1996) described schizencephaly as an extremely rare congenital disorder characterized by a full-thickness cleft within the cerebral hemispheres. The clefts are lined with gray matter and most commonly involve the parasylvian regions (Wolpert and Barnes, 1992). Large portions of the cerebral hemispheres may be absent and replaced by cerebrospinal fluid. Two types of schizencephaly have been described, depending on the size of the area involved and the separation of the cleft lips (Wolpert and Barnes, 1992). Type I schizencephaly consists of a fused cleft. This fused pial-ependymal seam forms a furrow in the developing brain, and is lined by polymicrogyric gray matter. In type II schizencephaly, there is a large defect, a holohemispheric cleft in the cerebral cortex filled with fluid and lined by polymicrogyric gray matter. The clinical manifestations depend on the severity of the lesion. Patients with type I are often almost normal; they may have seizures and spasticity. In type II abnormalities, there is usually mental retardation, seizures, hypotonia, spasticity, inability to walk or speak, and blindness.Schizencephaly may be part of the larger phenotypic spectrum of holoprosencephaly (HPE; see {236100}).

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

SOURCES: ORPHANET OMIM MENDELIAN

Pendred syndrome (PDS) is a clinically variable genetic disorder characterized by bilateral sensorineural hearing loss and euthyroid goiter.

PENDRED SYNDROME Is also known as thyroid hormonogenesis, genetic defect in, 2b|goiter-deafness syndrome|deafness with goiter|tdh2b|hypothyroidism, congenital, due to dyshormonogenesis, 2b|thyroid dyshormonogenesis 2b

• Intellectual disability
• Hearing impairment
• Ataxia
• Sensorineural hearing impairment
• Respiratory insufficiency

SOURCES: ORPHANET MESH OMIM MENDELIAN

Congenital hydrocephalus-1 is characterized by onset in utero of enlarged ventricles due to a disturbance of cerebrospinal fluid accumulation. Affected individuals may have neurologic impairment (summary by Drielsma et al., 2012).Hydrocephalus can also be caused by Arnold-Chiari malformation, atresia of foramen of Magendie, stenosis of aqueduct of Sylvius (OMIM ), toxoplasmosis, hydranencephaly, etc. Furthermore, it develops in infancy or childhood in achondroplasia (OMIM ) and in Hurler disease (OMIM ). Genetic Heterogeneity of Congenital HydrocephalusSee also HYC2 (OMIM ), caused by mutation in the MPDZ gene (OMIM ) on chromosome 9p23, and HYC3 (OMIM ), caused by mutation in the WDR81 gene (OMIM ) on chromosome 17p13.An X-linked form of congenital hydrocephalus (HSAS, HYCX; {307000}) is caused by mutation in the L1CAM gene on (OMIM ) on chromosome Xq28.

HYDROCEPHALUS, CONGENITAL, 1; HYC1 Is also known as hydrocephaly|hydrocephalus, nonsyndromic, autosomal recessive 1, formerly|ventriculomegaly

• Intellectual disability
• Seizures
• Neoplasm
• Macrocephaly
• Ventriculomegaly

SOURCES: OMIM ORPHANET MENDELIAN

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

SOURCES: ORPHANET MESH OMIM MENDELIAN

Beta-ureidopropionase deficiency is a very rare pyrimidine metabolism disorder described in fewer than 10 patients to date with an extremely wide clinical picture ranging from asymptomatic cases to neurological (epilepsy, autism) and developmental disorders (urogenital, colorectal).

BETA-UREIDOPROPIONASE DEFICIENCY Is also known as beta-alanine synthase deficiency

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

SOURCES: ORPHANET MESH OMIM MENDELIAN

Aminoacylase 1 deficiency (ACY1D) is an inborn error of metabolism marked by a characteristic pattern of urinary N-acetyl amino acid excretion and neurologic symptoms.

NEUROLOGICAL CONDITIONS ASSOCIATED WITH AMINOACYLASE 1 DEFICIENCY Is also known as n-acyl-l-amino acid amidohydrolase deficiency|acy1d

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Hearing impairment

SOURCES: OMIM ORPHANET MESH MENDELIAN