Dravet syndrome or genetic (generalized) epilepsy with febrile seizures plus?

Brain Dev. 2009 May;31(5):394-400. doi: 10.1016/j.braindev.2009.01.001. Epub 2009 Feb 8.


Dravet syndrome and genetic epilepsy with febrile seizures plus (GEFS+) can both arise due to mutations of SCN1A, the gene encoding the alpha 1 pore-forming subunit of the sodium channel. GEFS+ refers to a familial epilepsy syndrome where at least two family members have phenotypes that fit within the GEFS+ spectrum. The GEFS+ spectrum comprises a range of mild to severe phenotypes varying from classical febrile seizures to Dravet syndrome. Dravet syndrome is a severe infantile onset epilepsy syndrome with multiple seizure types, developmental slowing and poor outcome. More than 70% of patients with Dravet syndrome have mutations of SCN1A; these include both truncation and missense mutations. In contrast, only 10% of GEFS+ families have SCN1A mutations and these comprise missense mutations. GEFS+ has also been associated with mutations of genes encoding the sodium channel beta 1 subunit, SCN1B, and the GABA(A) receptor gamma 2 subunit, GABRG2. The phenotypic heterogeneity that is characteristic of GEFS+ families is likely to be due to modifier genes. Interpretation of the significance of a SCN1A missense mutation requires a thorough understanding of the phenotypes in the GEFS+ spectrum whereas a de novo truncation mutation is likely to be associated with a severe phenotype. Early recognition of Dravet syndrome is important as aggressive control of seizures may improve developmental outcome.

Publication types

  • Review

MeSH terms

  • Brain Chemistry / genetics
  • Epilepsies, Myoclonic / genetics*
  • Epilepsies, Myoclonic / metabolism
  • Epilepsies, Myoclonic / physiopathology
  • Epilepsy, Generalized / genetics*
  • Epilepsy, Generalized / metabolism
  • Epilepsy, Generalized / physiopathology
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Infant
  • Mutation, Missense / genetics
  • NAV1.1 Voltage-Gated Sodium Channel
  • Nerve Tissue Proteins / genetics*
  • Receptors, GABA-A / genetics
  • Seizures, Febrile / genetics*
  • Seizures, Febrile / metabolism
  • Seizures, Febrile / physiopathology
  • Sodium Channels / genetics*
  • Syndrome
  • Voltage-Gated Sodium Channel beta-1 Subunit


  • GABRG2 protein, human
  • NAV1.1 Voltage-Gated Sodium Channel
  • Nerve Tissue Proteins
  • Receptors, GABA-A
  • SCN1A protein, human
  • SCN1B protein, human
  • Sodium Channels
  • Voltage-Gated Sodium Channel beta-1 Subunit