Myers Kenneth A, Burgess Rosemary, Afawi Zaid, Damiano John A, Berkovic Samuel F, Hildebrand Michael S, Scheffer Ingrid E
Department of Medicine, Epilepsy Research Centre, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
Department of Pediatrics, Alberta Children's Hospital, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Epilepsia. 2017 Feb;58(2):e26-e30. doi: 10.1111/epi.13649. Epub 2017 Jan 13.
Genetic epilepsy with febrile seizures plus (GEFS+) is a familial epilepsy syndrome characterized by heterogeneous phenotypes ranging from mild disorders such as febrile seizures to epileptic encephalopathies (EEs) such as Dravet syndrome (DS). Although DS often occurs with de novo SCN1A pathogenic variants, milder GEFS+ spectrum phenotypes are associated with inherited pathogenic variants. We identified seven cases with non-EE GEFS+ phenotypes and de novo SCN1A pathogenic variants, including a monozygotic twin pair. Febrile seizures plus (FS+) occurred in six patients, five of whom had additional seizure types. The remaining case had childhood-onset temporal lobe epilepsy without known febrile seizures. Although early development was normal in all individuals, three later had learning difficulties, and the twin girls had language impairment and working memory deficits. All cases had SCN1A missense pathogenic variants that were not found in either parent. One pathogenic variant had been reported previously in a case of DS, and the remainder were novel. Our finding of de novo pathogenic variants in mild phenotypes within the GEFS+ spectrum shows that mild GEFS+ is not always inherited. SCN1A screening should be considered in patients with GEFS+ phenotypes because identification of pathogenic variants will influence antiepileptic therapy, and prognostic and genetic counseling.
伴有热性惊厥附加症的遗传性癫痫（GEFS+）是一种家族性癫痫综合征，其特征是具有异质性表型，范围从热性惊厥等轻度疾病到严重癫痫性脑病（EE），如Dravet综合征（DS）。虽然DS常伴有从头发生的SCN1A致病变异，但较轻的GEFS+谱系表型与遗传性致病变异相关。我们鉴定出7例具有非EE的GEFS+表型和从头发生的SCN1A致病变异的病例，其中包括一对同卵双胞胎。6例患者出现热性惊厥附加症（FS+），其中5例还有其他发作类型。其余1例为儿童期起病的颞叶癫痫，无热性惊厥病史。虽然所有个体的早期发育均正常，但3例后来出现学习困难，这对双胞胎女孩有语言障碍和工作记忆缺陷。所有病例均有SCN1A错义致病变异，其父母均未发现该变异。其中一个致病变异先前在1例DS患者中报道过，其余均为新发现的。我们在GEFS+谱系的轻度表型中发现从头发生的致病变异，表明轻度GEFS+并不总是遗传性的。对于具有GEFS+表型的患者应考虑进行SCN1A筛查，因为致病变异的鉴定将影响抗癫痫治疗以及预后和遗传咨询。
