Broad phenotypic heterogeneity due to a novel SCN1A mutation in a family with genetic epilepsy with febrile seizures plus

Hadassa Goldberg-Stern, Sharon Aharoni, Zaid Afawi, Odeya Bennett, Silke Appenzeller, Manuela Pendziwiat, Gregor Kuhlenbäumer, Lina Basel-Vanagaite, Avinoam Shuper, Amos D. Korczyn, Ingo Helbig

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


Genetic (generalized) epilepsy with febrile seizures plus is a familial epilepsy syndrome with marked phenotypic heterogeneity ranging from simple febrile seizure to severe phenotypes. Here we report on a large Israeli family with genetic (generalized) epilepsy with febrile seizures plus and 14 affected individuals. A novel SCN1A missense mutation in exon 21 (p.K1372E) was identified in all affected individuals and 3 unaffected carriers. The proband had Dravet syndrome, whereas febrile seizure plus phenotypes were present in all other affected family members. Simple febrile seizures were not observed. Phenotypes were found at both extremes of the genetic (generalized) epilepsy with febrile seizures plus spectrum and distribution of phenotypes suggested modifying familial, possibly genetic factors. We suggest that families with extreme phenotype distributions can represent prime candidates for the identification of genetic or environmental modifiers.

Original languageEnglish
Pages (from-to)221-226
Number of pages6
JournalJournal of Child Neurology
Issue number2
StatePublished - Feb 2014
Externally publishedYes

Bibliographical note

Funding Information:
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project was funded by intramural grants to IH by the University of Kiel and through grants by the German Research Foundation (DFG, HE 5413/3-1) to IH within the framework of the EuroEPINOMICS-RES project through the Eurocores program of the European Science Foundation (ESF).

Funding Information:
Work was performed at the Schneider Children's Hospital of Israel, Petach Tivka, Israel and at the Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Kiel. This project received infrastructural support from the Institute of Molecular Clinical Biololgy (ICMB), University of Kiel.


  • GEFS+
  • SCN1A
  • epilepsy genetics
  • febrile seizure


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