TY - JOUR
T1 - Genetic epilepsy with febrile seizures plus
AU - Zhang, Yue Hua
AU - Burgess, Rosemary
AU - Malone, Jodie P.
AU - Glubb, Georgie C.
AU - Helbig, Katherine L.
AU - Vadlamudi, Lata
AU - Kivity, Sara
AU - Afawi, Zaid
AU - Bleasel, Andrew
AU - Grattan-Smith, Padraic
AU - Grinton, Bronwyn E.
AU - Bellows, Susannah T.
AU - Vears, Danya F.
AU - Damiano, John A.
AU - Goldberg-Stern, Hadassa
AU - Korczyn, Amos D.
AU - DIbbens, Leanne M.
AU - Ruzzo, Elizabeth K.
AU - Hildebrand, Michael S.
AU - Berkovic, Samuel F.
AU - Scheffer, Ingrid E.
N1 - Publisher Copyright:
© 2017 American Academy of Neurology.
PY - 2017/9/19
Y1 - 2017/9/19
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85031048286&partnerID=8YFLogxK
U2 - 10.1212/WNL.0000000000004384
DO - 10.1212/WNL.0000000000004384
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C2 - 28842445
AN - SCOPUS:85031048286
VL - 89
SP - 1210
EP - 1219
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 12
ER -