Exploration of the genetic architecture of idiopathic generalized epilepsies

Anne Hempelmann, Kirsten P. Taylor, Armin Heils, Susanne Lorenz, Jean Francois Prud'Homme, Rima Nabbout, Olivier Dulac, Gabrielle Rudolf, Federico Zara, Amedeo Bianchi, Robert Robinson, R. Mark Gardiner, Athanasios Covanis, Dick Lindhout, Ulrich Stephani, Christian E. Elger, Yvonne G. Weber, Holger Lerche, Peter Nürnberg, Katherine L. KronIngrid E. Scheffer, John C. Mulley, Samuel F. Berkovic, Thomas Sander

Research output: Contribution to journalArticlepeer-review


Purpose: Idiopathic generalized epilepsy (IGE) accounts for ∼20% of all epilepsies and affects about 0.2% of the general population. The etiology of IGE is genetically determined, but the complex pattern of inheritance suggests an involvement of a large number of susceptibility genes. The objective of the present study was to explore the genetic architecture of common IGE syndromes and to dissect out susceptibility loci predisposing to absence or myoclonic seizures. Methods: Genome-wide linkage scans were performed in 126 IGE-multiplex families of European origin ascertained through a proband with idiopathic absence epilepsy or juvenile myoclonic epilepsy. Each family had at least two siblings affected by IGE. To search for seizure type-related susceptibility loci, linkage analyses were carried out in family subgroups segregating either typical absence seizures or myoclonic and generalized tonic-clonic seizures on awakening. Results: Nonparametric linkage scans revealed evidence for complex and heterogeneous genetic architectures involving linkage signals at 5q34, 6p12, 11q13, 13q22-q31, and 19q13. The signal patterns differed in their composition, depending on the predominant seizure type in the families. Conclusions: Our results are consistent with heterogeneous configurations of susceptibility loci associated with different IGE subtypes. Genetic determinants on 11q13 and 13q22-q31 seem to predispose preferentially to absence seizures, whereas loci on 5q34, 6p12, and 19q13 confer susceptibility to myoclonic and generalized tonic-clonic seizures on awakening.

Original languageEnglish
Pages (from-to)1682-1690
Number of pages9
Issue number10
Publication statusPublished - Oct 2006


  • Absence seizure
  • Complex inheritance
  • Idiopathic generalized epilepsy
  • Linkage
  • Myoclonic seizure

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)


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