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Genetics of epilepsy
  1. Dimitri M Kullmann
  1. Correspondence to:
 Professor Dimitri Kullmann, Institute of Neurology, Queen Square, London WC1N 3BG, UK;

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The last decade has witnessed rapid advances in understanding the role of genetic factors in epilepsy. Mutations and chromosomal defects underlying many inherited symptomatic epilepsies have now been identified, and several genes have been associated with rare idiopathic epilepsies transmitted in a mendelian manner. However, the genetic factors underlying inherited susceptibility to idiopathic epilepsy remain to be identified.


The International League Against Epilepsy (ILAE) Classification of epileptic syndromes (published in 1989) divides seizure disorders along two main axes. First, epilepsies are classified as idiopathic, symptomatic or cryptogenic, and second, they are either generalised or focal. Within this classification, genetic factors have conventionally been thought to play the largest role in the idiopathic generalised epilepsies. A genetically determined increased excitability of neuronal circuits provides an attractive explanation why otherwise normal individuals should develop unprovoked seizures without an identifiable focus of onset. This view has, moreover, been supported by the finding that concordance rates for idiopathic generalised epilepsy are elevated among first degree relatives, and more so among monozygotic twins. Similar arguments and evidence apply to febrile seizures, which do not count as an epilepsy syndrome as such. However, recent studies have shown that genetic factors also play an important role in cryptogenic epilepsy (seizure disorders where a syndromic diagnosis is not possible), and also contribute to several partial epilepsies. Also single gene defects have been identified in a small number of families with epilepsy inherited in an autosomal dominant fashion. These rare monogenic epilepsies have shed a new light on the mechanisms by which disorders of neuronal function can cause epilepsy. Major advances have also been made in establishing the cause of a number of rare but often severe symptomatic epilepsies.

This article will begin by considering a few genes responsible for symptomatic epilepsy, and then address recent progress in the …

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