The genetics of human epilepsy

Trends Pharmacol Sci. 2003 Aug;24(8):428-33. doi: 10.1016/S0165-6147(03)00194-9.

Abstract

In recent years genetic discoveries have shown the central role of ion channels in the pathophysiology of idiopathic epilepsies. Uncommon epilepsy syndromes that have monogenic inheritance are associated with mutations in genes that encode subunits of voltage-gated and ligand-gated ion channels. For voltage-gated ion channels, mutations of Na(+), K(+) and Cl(-) channels are associated with forms of generalized epilepsy and infantile seizure syndromes. Ligand-gated ion channels, such as nicotinic acetylcholine receptors and GABA receptor subunits, are associated with specific syndromes of frontal and generalized epilepsies, respectively. Striking features are the variable epilepsy phenotypes that are associated with the known gene mutations and the genetic heterogeneity that underlies all known monogenic syndromes. Mutations in two genes that do not encode ion channels have been identified in the idiopathic human epilepsies. The heterogeneity of mutations described to date has precluded the development of simple diagnostic tests, but advances in the next few years are likely to have an impact on both the clinical diagnosis and the treatment of epilepsies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Calcium Channels / genetics
  • Calcium Channels / physiology
  • Chloride Channels / genetics
  • Chloride Channels / physiology
  • Epilepsy / genetics*
  • Epilepsy / metabolism
  • Humans
  • Ligands
  • Mutation
  • Potassium Channels, Voltage-Gated / genetics
  • Potassium Channels, Voltage-Gated / physiology
  • Receptors, GABA / genetics
  • Receptors, GABA / physiology
  • Receptors, Nicotinic / genetics
  • Receptors, Nicotinic / physiology
  • Sodium Channels / genetics
  • Sodium Channels / physiology

Substances

  • Calcium Channels
  • Chloride Channels
  • Ligands
  • Potassium Channels, Voltage-Gated
  • Receptors, GABA
  • Receptors, Nicotinic
  • Sodium Channels