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.