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 ... 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).
Rauch et al. (2012) reported a German girl (MS134) with childhood-onset epileptic encephalopathy. She had delayed psychomotor development with an IQ of 50-69 and onset of absence seizures at age 5 years.
Carvill et al. (2013) ... Rauch et al. (2012) reported a German girl (MS134) with childhood-onset epileptic encephalopathy. She had delayed psychomotor development with an IQ of 50-69 and onset of absence seizures at age 5 years. Carvill et al. (2013) reported 6 unrelated patients with childhood-onset epileptic encephalopathy. The median age of seizure onset was 18 months (range, 1-3 years). All patients had myoclonic seizures in addition to variable seizure types, including absence, atonic, tonic, tonic-clonic, febrile, and status epilepticus. EEG studies showed multiple abnormalities. Four patients had developmental delay before the onset of seizures, 5 showed developmental regression after the onset of seizures, 3 had photosensitivity, and all had moderate to severe intellectual disability. One patient was diagnosed with autism spectrum disorder. The patients ranged in age from 2.5 to 29 years. Suls et al. (2013) reported 3 unrelated patients with onset of seizures associated with fever between the ages of 14 months and 3.5 years. All subsequently developed multiple seizure types, including myoclonic, atypical absence, generalized tonic-clonic, and status epilepticus, that were mostly therapy-resistant. EEG studies showed generalized polyspike-wave discharges. Two patients had normal development before the onset of seizures, whereas 1 patient had mildly delayed development before seizure onset. All had mild but persistent intellectual and neurologic impairment, including autism spectrum disorder in 1 patient.
In a German girl (MS134) with childhood-onset epileptic encephalopathy, Rauch et al. (2012) identified a de novo heterozygous truncating mutation in the CHD2 gene (602119.0001). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, ... In a German girl (MS134) with childhood-onset epileptic encephalopathy, Rauch et al. (2012) identified a de novo heterozygous truncating mutation in the CHD2 gene (602119.0001). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in either parent. The patient was ascertained from a large cohort of 51 patients with intellectual disability who underwent exome sequencing. Rauch et al. (2012) postulated haploinsufficiency as the disease mechanism. In 6 unrelated patients with childhood-onset epileptic encephalopathy, Carvill et al. (2013) identified 6 different de novo heterozygous mutations in the CHD2 gene (see, e.g., 602119.0002-602119.0006). Four of the mutations were truncating, and 2 were missense substitutions at highly conserved residues. The mutations were found by targeted sequencing of known or candidate genes in 500 individuals with epileptic encephalopathies and thus accounted for 1.2% of cases. Carvill et al. (2013) postulated haploinsufficiency as the disease mechanism. They noted that mutations in the related CHD7 gene (608892) cause developmental abnormalities. In 3 unrelated patients with childhood-onset epileptic encephalopathy, Suls et al. (2013) identified 3 different de novo heterozygous mutations in the CHD2 gene (602119.0007-602119.0009). The mutations in the first 2 patients were found by whole-exome sequencing of 9 probands with a similar disorder. The third patient was identified by sequencing of the CHD2 gene in 150 probands with epileptic encephalopathy. Suls et al. (2013) postulated that haploinsufficiency for CHD2 was responsible for the phenotype, and suggested that helicase dysfunction in humans may result in neuronal hyperexcitability in the absence of dysmorphic features.