Ataxia, and Heterotopia

• Intellectual disability
• Global developmental delay
• Microcephaly
• Ataxia
• Delayed speech and language development

SOURCES: OMIM MENDELIAN

Ataxia-intellectual disability-oculomotor apraxia-cerebellar cysts syndrome is a rare neuro-ophthalmological disease characterized by nonprogressive cerebellar ataxia, delayed motor and language development and intellectual disability, in addition to ophthalmological abnormalities (e.g. oculomotor apraxia, strabismus, amblyopia, retinal dystrophy and myopia). Cerebellar cysts, cerebellar dysplasia and cerebellar vermis hypoplasia, seen on magnetic resonance imaging, are also characteristic of the disease.

ATAXIA-INTELLECTUAL DISABILITY-OCULOMOTOR APRAXIA-CEREBELLAR CYSTS SYNDROME Is also known as poretti-boltshauser syndrome

• Intellectual disability
• Generalized hypotonia
• Ataxia
• Nystagmus
• Strabismus

SOURCES: OMIM ORPHANET MENDELIAN

Arnold-Chiari malformation type II is a rare, central nervous system malformation characterized by caudal displacement of the cerebellum, pons, medulla and fourth ventricle through the foramen magnum into the spinal canal, and is typically associated with myelomeningocele. Variable other central nervous system abnormalities might be present (partial or complete agenesis of the corpus callosum, a small fourth ventricle, obstructive hydrocephalus, falx and tentorium defects, and polygyria). Symptoms include hypotonia, apnea with cyanosis, dysphagia, opisthotonus, nystagmus, spasticity, ataxia, and occipital headache.

ARNOLD-CHIARI MALFORMATION TYPE II Is also known as cm2|arnold-chiari malformation|chiari malformation type ii|chiari malformation type 2|arnold-chiari malformation type 2

• Generalized hypotonia
• Ataxia
• Nystagmus
• Muscular hypotonia
• Spasticity

SOURCES: OMIM ORPHANET MENDELIAN

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

SOURCES: ORPHANET MESH OMIM MENDELIAN

Lissencephaly ('smooth brain') results from migrational arrest of cortical neurons short of their normal destination, and can result in profound mental retardation and seizures. In X-linked lissencephaly-1, affected males generally have more a severe phenotype compared to females. DCX mutations cause classic lissencephaly with mental retardation in hemizygous males and a milder phenotype known as subcortical band heterotopia in females, sometimes in the same family. The subcortical lamina heterotopia found in heterozygous females is also referred to as 'double cortex' (DC) syndrome (des Portes et al., 1997).There are several X-linked loci that affect neuronal migration, including the Aicardi locus (OMIM ).

LISSENCEPHALY, X-LINKED, 1; LISX1 Is also known as xlis|lissencephaly and agenesis of corpus callosum

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

SOURCES: OMIM MENDELIAN

Cerebellar ataxia, mental retardation, and dysequilibrium syndrome (CAMRQ) is a genetically heterogeneous disorder characterized by congenital cerebellar ataxia and mental retardation (summary by Gulsuner et al., 2011).For a discussion of genetic heterogeneity of CAMRQ, see CAMRQ1 (OMIM ).

CEREBELLAR ATAXIA, MENTAL RETARDATION, AND DYSEQUILIBRIUM SYNDROME 2; CAMRQ2 Is also known as cerebellar ataxia and mental retardation with or without quadrupedal locomotion 2

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

SOURCES: MESH OMIM MENDELIAN

OROFACIODIGITAL SYNDROME XVI; OFD16 Is also known as oral-facial-digital syndrome, type xvi|ofds xvi

• Global developmental delay
• Generalized hypotonia
• Ataxia
• Muscular hypotonia
• Ptosis

SOURCES: OMIM MENDELIAN

Joubert syndrome is an autosomal recessive congenital condition characterized by a unique brainstem and cerebellar malformation comprising cerebellar vermis hypoplasia and/or dysplasia, elongated superior cerebellar peduncles, and deepened interpeduncular fossa, which together are recognized as the 'molar tooth sign' on brain MRI. The most common clinical features include delayed psychomotor development, hypotonia, abnormal respiratory patterns in the neonatal period, oculomotor apraxia, and cerebellar ataxia. Additional features may include retinal degeneration, cystic kidney, liver fibrosis, and polydactyly. It is caused by ciliary defects and is part of a spectrum of disorders known as 'ciliopathies' (summary by Akizu et al., 2014).For a phenotypic description and a discussion of genetic heterogeneity of Joubert syndrome, see {213300}.

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

SOURCES: OMIM MENDELIAN

Genetic defects in the pyruvate dehydrogenase complex are one of the most common causes of primary lactic acidosis in children. Most cases are caused by mutation in the E1-alpha subunit gene on the X chromosome. X-linked PDH deficiency is one of the few X-linked diseases in which a high proportion of heterozygous females manifest severe symptoms. The clinical spectrum of PDH deficiency is broad, ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis (Robinson et al., 1987; Brown et al., 1994). Genetic Heterogeneity of Pyruvate Dehydrogenase Complex DeficiencyPDH deficiency can also be caused by mutation in other subunits of the PDH complex, including a form (PDHXD ) caused by mutation in the component X gene (PDHX ) on chromosome 11p13; a form (PDHBD ) caused by mutation in the PDHB gene (OMIM ) on chromosome 3p14; a form (PDHDD ) caused by mutation in the DLAT gene (OMIM ) on chromosome 11q23; a form (PDHPD ) caused by mutation in the PDP1 gene (OMIM ) on chromosome 8q22; and a form (PDHLD ) caused by mutation in the LIAS gene (OMIM ) on chromosome 4p14.

PYRUVATE DEHYDROGENASE E1-ALPHA DEFICIENCY; PDHAD Is also known as ataxia, intermittent, with pyruvate dehydrogenase deficiency|pyruvate decarboxylase deficiency|pdh deficiency|ataxia with lactic acidosis i|ataxia, intermittent, with abnormal pyruvate metabolism|pyruvate dehydrogenase complex deficiency

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

SOURCES: OMIM ORPHANET MENDELIAN

6q terminal deletion syndrome is marked by a characteristic facial dysmorphism, short neck and psychomotor retardation, generally associated with a range of non-specific malformations.

• Seizures
• Global developmental delay
• Scoliosis
• Hypertelorism
• Nystagmus

SOURCES: ORPHANET MENDELIAN