Abou-Khalil B, Ge Q, Desai R, Ryther R, Bazyk A, Bailey R, Haines J L, Sutcliffe J S, George A L
Department of Neurology, Vanderbilt University School of Medicine, Nashville, TN 37212, USA.
Neurology. 2001 Dec 26;57(12):2265-72. doi: 10.1212/wnl.57.12.2265.
Generalized epilepsy with febrile seizures plus (GEFS+) is an autosomal dominant syndrome characterized by febrile seizures (FS) and a variety of afebrile generalized seizure types. GEFS+ has previously been linked to mutations in two genes encoding the voltage-gated sodium channel alpha-subunit (SCN1A) and beta1-subunit (SCN1B). We studied a large family with FS and partial as well as generalized seizure types.
All but two living affected family members were interviewed and examined. Information on deceased affected family members was sought. EEG for 11 affected family members and one unaffected family member were obtained. Genetic linkage analysis and mutation screening of SCN1A were performed on blood samples from 16 affected individuals and their first-degree relatives.
There were 27 affected family members; 18 were alive at the time of the study. All affected family members had FS; seven had FS only, and 19 also had afebrile seizures. Eleven individuals continued to have FS beyond 6 years of age. FS were complex in 12 family members, usually with prolonged duration. The index patient had right temporal lobe epilepsy and hippocampal sclerosis. Four other patients had strong historical evidence of temporal lobe epilepsy, and three others had nonlocalizing evidence of partial epilepsy. Pedigree analysis indicated autosomal dominant transmission. All affected individuals who were tested and one asymptomatic individual had a sodium channel mutation of SCN1A, an A-->C transversion at nucleotide 3809 resulting in the substitution of lysine 1270 by threonine in the D3/S2 segment (designated as K1270T).
Our findings indicate that partial epilepsy preceded by FS can be associated with sodium channel mutations and may represent a variant of GEFS+.
伴有热性惊厥附加症的全身性癫痫（GEFS+）是一种常染色体显性综合征，其特征为热性惊厥（FS）和多种无热全身性癫痫发作类型。此前，GEFS+已与编码电压门控钠通道α亚基（SCN1A）和β1亚基（SCN1B）的两个基因突变相关。我们研究了一个患有FS以及部分性和全身性癫痫发作类型的大家庭。
除两名在世的患病家庭成员外，对所有其他患病家庭成员进行了访谈和检查。还收集了已故患病家庭成员的信息。对11名患病家庭成员和1名未患病家庭成员进行了脑电图检查。对16名患病个体及其一级亲属的血样进行了SCN1A的基因连锁分析和突变筛查。
有27名患病家庭成员；研究时18人在世。所有患病家庭成员都有FS；7人仅有FS，19人也有无热惊厥。11人6岁后仍有FS。12名家庭成员的FS为复杂性，通常持续时间较长。索引患者患有右颞叶癫痫和海马硬化。另外4名患者有颞叶癫痫的有力病史证据，还有3名患者有部分性癫痫的非定位证据。系谱分析表明为常染色体显性遗传。所有接受检测的患病个体和1名无症状个体都有SCN1A钠通道突变，即核苷酸3809处的A→C颠换，导致D3/S2区段的赖氨酸1270被苏氨酸替代（命名为K1270T）。
我们的研究结果表明，FS前驱的部分性癫痫可能与钠通道突变有关，可能代表GEFS+的一种变异型。
