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

doi:10.1177/0883073813509016

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 journal › Article › peer-review

49 Scopus citations

Abstract

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 language	English
Pages (from-to)	221-226
Number of pages	6
Journal	Journal of Child Neurology
Volume	29
Issue number	2
DOIs	https://doi.org/10.1177/0883073813509016
State	Published - Feb 2014
Externally published	Yes

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.

Funding

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). 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.

Funders	Funder number
ICMB
Institute of Molecular Clinical Biololgy
University of Kiel
European Science Foundation
Deutsche Forschungsgemeinschaft	HE 5413/3-1

Keywords

GEFS+
SCN1A
epilepsy genetics
febrile seizure

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10.1177/0883073813509016

Cite this

Goldberg-Stern, H., Aharoni, S., Afawi, Z., Bennett, O., Appenzeller, S., Pendziwiat, M., Kuhlenbäumer, G., Basel-Vanagaite, L., Shuper, A., Korczyn, A. D., & Helbig, I. (2014). Broad phenotypic heterogeneity due to a novel SCN1A mutation in a family with genetic epilepsy with febrile seizures plus. Journal of Child Neurology, 29(2), 221-226. https://doi.org/10.1177/0883073813509016

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

abstract = "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.",

keywords = "GEFS+, SCN1A, epilepsy genetics, febrile seizure",

author = "Hadassa Goldberg-Stern and Sharon Aharoni and Zaid Afawi and Odeya Bennett and Silke Appenzeller and Manuela Pendziwiat and Gregor Kuhlenb{\"a}umer and Lina Basel-Vanagaite and Avinoam Shuper and Korczyn, {Amos D.} and Ingo Helbig",

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. ",

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doi = "10.1177/0883073813509016",

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Goldberg-Stern, H, Aharoni, S, Afawi, Z, Bennett, O, Appenzeller, S, Pendziwiat, M, Kuhlenbäumer, G, Basel-Vanagaite, L, Shuper, A, Korczyn, AD & Helbig, I 2014, 'Broad phenotypic heterogeneity due to a novel SCN1A mutation in a family with genetic epilepsy with febrile seizures plus', Journal of Child Neurology, vol. 29, no. 2, pp. 221-226. https://doi.org/10.1177/0883073813509016

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

Abstract

Bibliographical note

Funding

Keywords

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