From the Epilepsy Research Centre, Department of Medicine (Y.-H.Z., R.B., J.P.M., G.C.G., K.L.H., L.V., B.E.G., S.T.B., D.F.V., J.A.D., M.S.H., S.F.B., I.E.S.), The University of Melbourne, Austin Health, Australia; Department of Pediatrics (Y.-H.Z.), Peking University First Hospital, Beijing, China; Department of Neurology (L.V.), The University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, Australia; Schneider Children's Medical Center of Israel (S.K., H.G.-S.), Petach Tikvah; Department of Neurology (Z.A.), Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel; Westmead Hospital (A.B.), New South Wales, Australia; Department of Neurology (P.G.-S.), Sydney Children's Hospital, Australia; Department of Neurology (A.D.K.), Tel Aviv University, Israel; Women's and Children's Hospital (L.M.D.), University of Adelaide, South Australia; Center for Neurobehavioral Genetics (E.K.R.), Semel Institute, David Geffen School of Medicine, University of California, Los Angeles; Department of Paediatrics (I.E.S.), The University of Melbourne, Royal Children's Hospital, Victoria; and The Florey Institute of Neurosciences and Mental Health (I.E.S.), Melbourne, Australia.
Neurology. 2017 Sep 19;89(12):1210-1219. doi: 10.1212/WNL.0000000000004384. Epub 2017 Aug 25.
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.
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.
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.
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.
继 1997 年我们对热性惊厥附加全面性癫痫（GEFS+）的原始描述后，我们分析了 60 个家系中的 409 名受影响个体（31 个新家系）的表型谱，并扩展了 GEFS+谱。
我们对所有可利用的受影响家族成员进行了详细的电临床表型分析。在可能的情况下，对已知的 GEFS+基因进行了遗传分析。我们将我们的表型和遗传数据与过去 19 年文献中发表的数据进行了比较。
我们在 GEFS+谱内确定了新的表型：无热性惊厥前驱的局灶性发作（16/409[4%]）、经典遗传性全面性癫痫（22/409[5%]）和无热全身性强直-阵挛发作（9/409[2%]）。热性惊厥仍然是 GEFS+中最常见的表型（178/409[44%]），其次是热性惊厥附加（111/409[27%]）。三分之一（50/163[31%]）经测试的 GEFS+家系在已知的 GEFS+基因中存在致病性变异。
由于 163 名受影响个体中有 37 名（9%）患有局灶性癫痫，我们建议将 GEFS+更名为热性惊厥附加的遗传性癫痫，而不是热性惊厥附加的全面性癫痫。GEFS+与经典全面性癫痫之间的表型重叠比最初想象的要大得多。临床和分子数据表明，这 2 大组全面性癫痫具有共同的遗传决定因素。
