Intellectual disability, and Developmental regression

This is an autosomal recessive disorder resulting from brain-specific folate deficiency early in life. Onset is apparent in late infancy with severe developmental regression, movement disturbances, epilepsy, and leukodystrophy. Recognition and diagnosis of this disorder is critical because folinic acid therapy can reverse the clinical symptoms and improve brain abnormalities and function (Steinfeld et al., 2009).

• Intellectual disability
• Seizures
• Developmental regression
• Neurodegeneration
• Leukodystrophy

SOURCES: ORPHANET OMIM MESH MENDELIAN

Nocturnal frontal lobe epilepsy-5 is an autosomal dominant focal epilepsy syndrome characterized by childhood onset of clusters of motor seizures during sleep. Some patients may develop behavioral or psychiatric manifestations and/or intellectual disability. The phenotype is more severe than observed in other genetic forms of ENFL (summary by Heron et al., 2012).For a general description and a discussion of genetic heterogeneity of ENFL, see ENFL1 (OMIM ).

• Intellectual disability
• Seizures
• Cognitive impairment
• Behavioral abnormality
• Depressivity

SOURCES: OMIM MENDELIAN

Childhood-onset epileptic encephalopathy (EEOC) is a severe form of epilepsy characterized by onset of multiple seizure types in the first few years of life and associated with poor prognosis. Affected individuals have cognitive regression and intellectual disability (summary by Carvill et al., 2013).

• Intellectual disability
• Seizures
• Global developmental delay
• Fever
• Encephalopathy

SOURCES: OMIM MENDELIAN

X-linked autism-6 is a neurodevelopmental disorder that affects only males. Some patients may respond favorably to carnitine supplementation (summary by Ziats et al., 2015).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, stereotypic, 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).For a discussion of heterogeneity of autism, see {209850}.

AUTISM, SUSCEPTIBILITY TO, X-LINKED 6; AUTSX6 Is also known as tmlhed|epsilon-trimethyllysine hydroxylase deficiency

• Intellectual disability
• Seizures
• Ptosis
• Delayed speech and language development
• Atrial septal defect

SOURCES: OMIM MENDELIAN

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

SOURCES: OMIM MENDELIAN

Myoclonic Astatic Epilepsy (MAE) is a rare epilepsy syndrome of childhood characterized by the occurrence of multiple different seizure types including myoclonic-astatic, generalized tonic-clonic and absence seizures, usually in previously healthy children.

MYOCLONIC-ASTASTIC EPILEPSY Is also known as mae|emas|myoclonic atonic epilepsy|doose syndrome|epilepsy with myoclonic-astatic seizures|myoclonic-astatic epilepsy in early childhood|epilepsy with myoclonic-atonic seizures

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

SOURCES: ORPHANET OMIM MENDELIAN

FAMILIAL INFANTILE MYOCLONIC EPILEPSY Is also known as fime|eim|familial infantile myoclonus epilepsy

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

SOURCES: OMIM ORPHANET MENDELIAN

Early infantile epileptic encephalopathy-37 is an autosomal recessive severe epileptic-dyskinetic disorder characterized by onset of intractable seizures or abnormal movements in the first years of life. Affected individuals show global developmental delay and/or developmental regression after onset of seizures. Patients also show a hyperkinetic movement disorder with choreoathetosis, spasticity, and rigidity. The individuals are severely affected, with mental retardation, absent speech, and impaired volitional movements (summary by Madeo et al., 2016).For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (OMIM ).

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

SOURCES: OMIM MENDELIAN

IECEE1 is a neurodevelopmental disorder characterized by delayed psychomotor development apparent in infancy and resulting in severe to profound intellectual disability with poor or absent speech. Most patients never achieve independent walking. Patients typically have onset of refractory multifocal seizures between the first weeks and years of life, and some may show developmental regression. Additional features, such as hypotonia and cortical visual impairment, are more variable (summary by Myers et al., 2017). Genetic Heterogeneity of Infantile or Early Childhood Epileptic EncephalopathySee also IECEE2 (OMIM ), caused by mutation in the GABRB2 gene (OMIM ) on chromosome 5q34, and IECEE3 (OMIM ), caused by mutation in the ATP6V1A gene (OMIM ) on chromosome 3q13.

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

SOURCES: OMIM MENDELIAN

Early infantile epileptic encephalopathy-34 is an autosomal recessive severe neurologic disorder characterized by onset of refractory migrating focal seizures in infancy. Affected children show developmental regression and are severely impaired globally (summary by Stodberg et al., 2015).For a discussion of genetic heterogeneity of EIEE, see {308350}.

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Cerebral atrophy

SOURCES: OMIM MENDELIAN