Genetic epilepsy with febrile seizures plus: Refining the spectrum

Neurology. 2017 Sep 19;89(12):1210-1219. doi: 10.1212/WNL.0000000000004384. Epub 2017 Aug 25.

Abstract

Objective: Following our original description of generalized epilepsy with febrile seizures plus (GEFS+) in 1997, we analyze the phenotypic spectrum in 409 affected individuals in 60 families (31 new families) and expand the GEFS+ spectrum.

Methods: We performed detailed electroclinical phenotyping on all available affected family members. Genetic analysis of known GEFS+ genes was carried out where possible. We compared our phenotypic and genetic data to those published in the literature over the last 19 years.

Results: We identified new phenotypes within the GEFS+ spectrum: focal seizures without preceding febrile seizures (16/409 [4%]), classic genetic generalized epilepsies (22/409 [5%]), and afebrile generalized tonic-clonic seizures (9/409 [2%]). Febrile seizures remains the most frequent phenotype in GEFS+ (178/409 [44%]), followed by febrile seizures plus (111/409 [27%]). One third (50/163 [31%]) of GEFS+ families tested have a pathogenic variant in a known GEFS+ gene.

Conclusion: As 37/409 (9%) affected individuals have focal epilepsies, we suggest that GEFS+ be renamed genetic epilepsy with febrile seizures plus rather than generalized epilepsy with febrile seizures plus. The phenotypic overlap between GEFS+ and the classic generalized epilepsies is considerably greater than first thought. The clinical and molecular data suggest that the 2 major groups of generalized epilepsies share genetic determinants.

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Child
  • Child, Preschool
  • Epilepsies, Partial / genetics
  • Epilepsies, Partial / physiopathology*
  • Epilepsy, Generalized / genetics
  • Epilepsy, Generalized / physiopathology*
  • Female
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Pedigree
  • Phenotype
  • Seizures, Febrile / genetics
  • Seizures, Febrile / physiopathology*
  • Young Adult