Ataxia, and Autism

Medium match MEGALENCEPHALIC LEUKOENCEPHALOPATHY WITH SUBCORTICAL CYSTS 2B, REMITTING, WITH OR WITHOUT MENTAL RETARDATION; MLC2B

Autosomal dominant remitting MLC2B is characterized by infantile-onset of macrocephaly and mildly delayed motor development associated with white matter abnormalities on brain MRI that improve with age. As children, some patients have mild residual hypotonia or clumsiness, but otherwise have no residual motor abnormalities. About 40% of patients have mental retardation (summary by van der Knaap et al., 2010 and Lopez-Hernandez et al., 2011).Homozygous or compound heterozygous mutations in the HEPACAM gene can cause a more severe and progressive disorder associated with ataxia, spasticity, and mental retardation (MLC2A ).For a discussion of genetic heterogeneity of megalencephalic leukoencephalopathy with subcortical cysts, see MLC1 (OMIM ).

• Intellectual disability
• Generalized hypotonia
• Ataxia
• Spasticity
• Motor delay

SOURCES: OMIM MENDELIAN

Medium match MENTAL RETARDATION, AUTOSOMAL DOMINANT 55, WITH SEIZURES; MRD55

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

SOURCES: OMIM MENDELIAN

Medium match AUTISM, SUSCEPTIBILITY TO, X-LINKED 4; AUTSX4

Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypical, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; {608638}) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006).Levy et al. (2009) provided a general review of autism and autism spectrum disorder, including epidemiology, characteristics of the disorder, diagnosis, neurobiologic hypotheses for the etiology, genetics, and treatment options.

AUTISM, SUSCEPTIBILITY TO, X-LINKED 4; AUTSX4 Is also known as chromosome xp22 deletion syndrome

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

SOURCES: OMIM MENDELIAN

Medium match INTELLECTUAL DEVELOPMENTAL DISORDER WITH OR WITHOUT EPILEPSY OR CEREBELLAR ATAXIA; IDDECA

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

SOURCES: OMIM MENDELIAN

Medium match EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 59; EIEE59

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

SOURCES: OMIM MENDELIAN

Medium match SUCCINIC SEMIALDEHYDE DEHYDROGENASE DEFICIENCY

Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare neurometabolic disorder of gamma-aminobutyric acid (GABA) metabolism with a nonspecific clinical presentation (ranging from mild to severe) with the most frequent symptoms being cognitive impairment with prominent deficit in expressive language, hypotonia, ataxia, epilepsy, and behavioral dysregulation.

SUCCINIC SEMIALDEHYDE DEHYDROGENASE DEFICIENCY Is also known as ssadh deficiency|4-hydroxybutyric aciduria|gaba metabolic defect|gamma-hydroxybutyric aciduria

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

SOURCES: OMIM MESH ORPHANET MENDELIAN

Medium match FEMALE RESTRICTED EPILEPSY WITH INTELLECTUAL DISABILITY

Female restricted epilepsy with intellectual disability is a rare X-linked epilepsy syndrome characterized by febrile or afebrile seizures (mainly tonic-clonic, but also absence, myoclonic, and atonic) starting in the first years of life and, in most cases, developmental delay and intellectual disability of variable severity. Behavioral disturbances (e.g. autistic features, hyperactivity, and aggressiveness) are also frequently associated. This disease affects exclusively females, with male carriers being unaffected, despite an X-linked inheritance.

FEMALE RESTRICTED EPILEPSY WITH INTELLECTUAL DISABILITY Is also known as juberg-hellman syndrome|efmr|epilepsy, female-restricted, with mental retardation

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

SOURCES: ORPHANET MESH OMIM MENDELIAN

Medium match EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 13; EIEE13

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

SOURCES: OMIM MENDELIAN

Medium match MENTAL RETARDATION, AUTOSOMAL DOMINANT 5; MRD5

MRD5 is characterized by moderate to severe intellectual disability with delayed psychomotor development apparent in the first years of life. Most patients develop variable types of seizures, some have autism or autism spectrum disorder (see {209850}), and some have acquired microcephaly (summary by Berryer et al., 2013).

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

SOURCES: OMIM MESH MENDELIAN

Medium match EPILEPSY, FOCAL, WITH SPEECH DISORDER AND WITH OR WITHOUT MENTAL RETARDATION; FESD

Focal epilepsy with speech disorder is a childhood-onset seizure disorder with a highly variable phenotype. Seizures typically occur in the temporal lobe, or rolandic brain region, which affects speech and language, and electroencephalogram (EEG) characteristically shows centrotemporal spike-wave discharges. EEG abnormalities often occur during sleep and may manifest as continuous spike-wave discharges during slow-wave sleep (CSWS or CSWSS). FESD represents an electroclinical spectrum that ranges from severe early-onset seizures associated with delayed psychomotor development, persistent speech difficulties, and mental retardation to a more benign entity characterized by childhood onset of mild or asymptomatic seizures associated with transient speech difficulties followed by remission of seizures in adolescence and normal psychomotor development. There is incomplete penetrance and intrafamilial variability, even among family members who carry the same GRIN2A mutation (summary by Lesca et al., 2013; Lemke et al., 2013; Carvill et al., 2013).The disorder represented here encompasses several clinical entities, including Landau-Kleffner syndrome (LKS), epileptic encephalopathy with continuous spike and wave during slow-wave sleep (ECSWS; CSWSS), autosomal dominant rolandic epilepsy, mental retardation, and speech dyspraxia (ADRESD; RESDAD), and benign epilepsy with centrotemporal spikes (BECTS; see {117100}). LKS is classically described as a childhood-onset variant of epileptic aphasia. It is associated with EEG abnormalities occurring in the temporal lobe of the language-dominant hemisphere, even in the absence of overt clinical seizures. LKS is sometimes referred to as an 'acquired aphasia' because most affected children show normal psychomotor development until the onset of seizures, usually between 3 and 7 years, although some may have prior delayed development. A hallmark of the disorder is severe impairment in auditory language comprehension and speech. Some patients may also have persistent intellectual disability or behavioral abnormalities reminiscent of autism or attention deficit-hyperactivity disorder. EEG abnormalities typically include centrotemporal spikes suggestive of rolandic epilepsy or continuous spike and waves during slow-wave sleep. The presence of CSWS is associated with more widespread behavioral and cognitive regression than LKS, although the 2 disorders may be considered part of a spectrum. There is controversy about the precise definition of LKS and its relationship to CSWS that stems mainly from the phenotypic heterogeneity of the disorder (summary by Stefanatos, 2011).

EPILEPSY, FOCAL, WITH SPEECH DISORDER AND WITH OR WITHOUT MENTAL RETARDATION; FESD Is also known as aphasia, acquired, with epilepsy

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

SOURCES: OMIM MENDELIAN