Genetic epilepsy with febrile seizures plus

Yue Hua Zhang, Rosemary Burgess, Jodie P. Malone, Georgie C. Glubb, Katherine L. Helbig, Lata Vadlamudi, Sara Kivity, Zaid Afawi, Andrew Bleasel, Padraic Grattan-Smith, Bronwyn E. Grinton, Susannah T. Bellows, Danya F. Vears, John A. Damiano, Hadassa Goldberg-Stern, Amos D. Korczyn, Leanne M. DIbbens, Elizabeth K. Ruzzo, Michael S. Hildebrand, Samuel F. BerkovicIngrid E. Scheffer

Research output: Contribution to journalArticlepeer-review

115 Scopus citations


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.

Original languageEnglish
Pages (from-to)1210-1219
Number of pages10
Issue number12
StatePublished - 19 Sep 2017
Externally publishedYes

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© 2017 American Academy of Neurology.


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