Goldberg-Stern Hadassa, Aharoni Sharon, Afawi Zaid, Bennett Odeya, Appenzeller Silke, Pendziwiat Manuela, Kuhlenbäumer Gregor, Basel-Vanagaite Lina, Shuper Avinoam, Korczyn Amos D, Helbig Ingo
1Department of Pediatric and Adolescent Neurology, Epilepsy Center, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
J Child Neurol. 2014 Feb;29(2):221-6. doi: 10.1177/0883073813509016. Epub 2013 Nov 20.
Genetic (generalized) epilepsy with febrile seizures plus is a familial epilepsy syndrome with marked phenotypic heterogeneity ranging from simple febrile seizure to severe phenotypes. Here we report on a large Israeli family with genetic (generalized) epilepsy with febrile seizures plus and 14 affected individuals. A novel SCN1A missense mutation in exon 21 (p.K1372E) was identified in all affected individuals and 3 unaffected carriers. The proband had Dravet syndrome, whereas febrile seizure plus phenotypes were present in all other affected family members. Simple febrile seizures were not observed. Phenotypes were found at both extremes of the genetic (generalized) epilepsy with febrile seizures plus spectrum and distribution of phenotypes suggested modifying familial, possibly genetic factors. We suggest that families with extreme phenotype distributions can represent prime candidates for the identification of genetic or environmental modifiers.
伴有热性惊厥附加症的遗传性（全身性）癫痫是一种家族性癫痫综合征，具有显著的表型异质性，范围从单纯热性惊厥到严重表型。在此，我们报告一个大型以色列家族，该家族患有伴有热性惊厥附加症的遗传性（全身性）癫痫，有14名受影响个体。在所有受影响个体和3名未受影响的携带者中鉴定出一个位于外显子21的新型SCN1A错义突变（p.K1372E）。先证者患有德雷维特综合征，而所有其他受影响家庭成员均表现为热性惊厥附加症表型。未观察到单纯热性惊厥。在伴有热性惊厥附加症的遗传性（全身性）癫痫谱的两个极端均发现了表型，表型分布提示存在修饰性家族性因素，可能是遗传因素。我们认为，具有极端表型分布的家族可能是鉴定遗传或环境修饰因子的主要候选对象。
