Genetics of idiopathic generalized epilepsies.
The idiopathic generalized epilepsies (IGEs) are considered to be primarily genetic in origin. They encompass a number of rare mendelian or monogenic epilepsies and more common forms which are familial but manifest as complex, non-mendelian traits. Recent advances have demonstrated that many monogenic IGEs are ion channelopathies. These include benign familial neonatal convulsions due to mutations in KCNQ2 or KCNQ3, generalized epilepsy with febrile seizures plus due to mutations in SCN1A, SCN2A, SCN1B, and GABRG2, autosomal-dominant juvenile myoclonic epilepsy (JME) due to a mutation in GABRA1 and mutations in CLCN2 associated with several IGE sub-types. There has also been progress in understanding the non-mendelian IGEs. A haplotype in the Malic Enzyme 2 gene, ME2, increases the risk for IGE in the homozygous state. Five missense mutations have been identified in EFHC1 in 6 of 44 families with JME. Rare sequence variants have been identified in CACNA1H in sporadic patients with childhood absence epilepsy in the Chinese Han population. These advances should lead to new approaches to diagnosis and treatment.
Gardiner
Mark
M
Department of Paediatrics and Child Health, Royal Free and University College Medical School, University College London, London, UK. mark.gardiner@ucl.ac.uk
D004829:Epilepsy, Generalized / Q000145:classification / Q000235:genetics*; D008040:Genetic Linkage; D006801:Humans; D007473:Ion Channels / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010641:Phenotype
D007473:Ion Channels