A case report of a family with overlapping features of autosomal dominant febrile seizures and GEFS+

Epilepsia. 2009 Apr;50(4):937-42. doi: 10.1111/j.1528-1167.2008.01876.x. Epub 2008 Nov 19.

Abstract

Familial febrile seizures occur in both generalized epilepsy with febrile seizures plus (GEFS+) and autosomal dominant febrile seizures (ADFS). The literature largely separates families with GEFS+ from those with ADFS. However, there is clinical overlap, and families with ADFS also include individuals with afebrile seizures. The phenotypic spectrum of GEFS+ is broader now than when first described, resulting in unclear boundaries between these two familial syndromes. The purpose of this report is to highlight the phenotypic similarities of GEFS+ and ADFS. A multigenerational family with febrile and afebrile seizures is described and the clinical features are compared to those of previously reported GEFS+ and ADFS families. This family meets the requirements for both ADFS and the broader definition of GEFS+. Linkage analysis has shown no clear linkage to known febrile seizure or GEFS+ loci. Despite locus heterogeneity, identified mutations in reported GEFS+ have so far all been in sodium channel or gamma-aminobutyric acid (GABA)-receptor genes, with other modifier genes postulated to affect individual phenotypes. The two mutations identified in families with ADFS are in genes implicated in GEFS+, SCN1A, and GABRG2. We conclude that it is inappropriate to separate GEFS+ and ADFS at present given the clinical and genotypic overlap.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Child, Preschool
  • DNA Mutational Analysis
  • Electroencephalography
  • Epilepsy, Generalized / complications*
  • Epilepsy, Generalized / genetics
  • Family Health*
  • Female
  • Genetic Linkage
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • NAV1.1 Voltage-Gated Sodium Channel
  • Nerve Tissue Proteins / genetics
  • Phenotype
  • Receptors, GABA-A / genetics
  • Seizures, Febrile / complications*
  • Seizures, Febrile / genetics
  • Sodium Channels / genetics
  • Young Adult

Substances

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