title: Channelopathies in idiopathic epilepsy.
abstract: Approximately 70% of all patients with epilepsy lack an obvious extraneous cause and are presumed to have a predominantly genetic basis. Both familial and de novo mutations in neuronal voltage-gated and ligand-gated ion channel subunit genes have been identified in autosomal dominant epilepsies. However, patients with dominant familial mutations are rare and the majority of idiopathic epilepsy is likely to be the result of polygenic susceptibility alleles (complex epilepsy). Data on the identity of the genes involved in complex epilepsy is currently sparse but again points to neuronal ion channels. The number of genes and gene families associated with epilepsy is rapidly increasing and this increase is likely to escalate over the coming years with advances in mutation detection technologies. The genetic heterogeneity underlying idiopathic epilepsy presents challenges for the rational selection of therapies targeting particular ion channels. Too little is currently known about the genetic architecture of the epilepsies, and genetic testing for the known epilepsy genes remains costly. Pharmacogenetic studies have yet to explain why 30% of patients do not respond to the usual antiepileptic drugs. Despite this, the recognition that the idiopathic epilepsies are a group of channelopathies has, to a limited extent, explained the therapeutic action of the common antiepileptic drugs and has assisted clinical diagnosis of some epilepsy syndromes.
authors: Department of Genetic Medicine, Women's and Children's Hospital, North Adelaide, South Australia 5006. sarah.heron@cywhs.sa.gov.au
authors: Sarah E
authors: SE
authors: Heron
authors: Ingrid E
authors: IE
authors: Scheffer
authors: Samuel F
authors: SF
authors: Berkovic
authors: Leanne M
authors: LM
authors: Dibbens
authors: John C
authors: JC
authors: Mulley
mesh_terms: D000818:Animals; D053447:Channelopathies / Q000150:complications* / Q000235:genetics*; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism; D004827:Epilepsy / Q000209:etiology* / Q000235:genetics*; D005192:Family Health; D006801:Humans; D011950:Receptors, Cholinergic / Q000235:genetics / Q000378:metabolism; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism
chemical_list: D018118:Chloride Channels; D011950:Receptors, Cholinergic; D018079:Receptors, GABA; D015222:Sodium Channels