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.
| Original language | English |
|---|---|
| Pages (from-to) | 1210-1219 |
| Number of pages | 10 |
| Journal | Neurology |
| Volume | 89 |
| Issue number | 12 |
| DOIs | |
| State | Published - 19 Sep 2017 |
| Externally published | Yes |
Bibliographical note
Funding Information:Y. Zhang, R. Burgess, J. Malone, G. Glubb, K. Helbig, L. Vadlamudi, S. Kivity, Z. Afawi, A. Bleasel, P. Grattan-Smith, B. Grinton, S. Bellows, D. Vears, J. Damiano, H. Goldberg-Stern, A. Korczyn, L. Dibbens, E. Ruzzo, and M. Hildebrand report no disclosures relevant to the manuscript. S. Berkovic has served on scientific advisory boards for UCB and Janssen-Cilag; serves on the editorial boards of Lancet Neurology and Epileptic Disorders and the Advisory Board of Brain; may accrue future revenue on pending patent WO61/010176: Therapeutic Compound that relates to discovery of PCDH19 gene as the cause of familial epilepsy with mental retardation limited to females; is one of the inventors listed on a patent held by Bionomics Inc. on diagnostic testing of using the SCN1A gene, WO2006/133508; has received speaker honoraria from UCB; has received unrestricted educational grants from UCB, Janssen-Cilag, and Sanofi-Aventis; and receives/has received research support from the National Health and Medical Research Council of Australia and NINDS. I. Scheffer serves on the editorial boards of the Annals of Neurology, Neurology®, and Epileptic Disorders; may accrue future revenue on a pending patent WO61/010176: Therapeutic Compound that relates to discovery of PCDH19 gene as the cause of familial epilepsy with mental retardation limited to females; is one of the inventors listed on a patent held by Bionomics Inc. on diagnostic testing of using the SCN1A gene, WO2006/133508; has received speaker honoraria from Athena Diagnostics, UCB, GSK, and Transgenomics; has received funding for travel from Athena Diagnostics, UCB, and GSK; and receives/has received research support from the National Health and Medical Research Council of Australia and NINDS. Go to Neurology.org for full disclosures.
Funding Information:
This work was supported by the National Health and Medical Research Council of Australia (Program Grant 628952, 2011–2015, to S.F.B., I.E. S., L.M.D.; Program Grant 1091593, 2016–2020, to S.F.B. and I.E.S.), Australia Fellowship (466671 to S.F.B.), Senior Practitioner Fellowship (1006110, 2011–2015; 1104831, 2016–2020; to I.E.S.), and Career Development Fellowship (1032603 to LMD and 1063799 to M.S.H.).
Publisher Copyright:
© 2017 American Academy of Neurology.