Harkin Louise A, McMahon Jacinta M, Iona Xenia, Dibbens Leanne, Pelekanos James T, Zuberi Sameer M, Sadleir Lynette G, Andermann Eva, Gill Deepak, Farrell Kevin, Connolly Mary, Stanley Thorsten, Harbord Michael, Andermann Frederick, Wang Jing, Batish Sat Dev, Jones Jeffrey G, Seltzer William K, Gardner Alison, Sutherland Grant, Berkovic Samuel F, Mulley John C, Scheffer Ingrid E
Department of Genetic Medicine, Women's and Children's Hospital, North Adelaide, South Australia.
Brain. 2007 Mar;130(Pt 3):843-52. doi: 10.1093/brain/awm002.
The relationship between severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome) and the related syndrome SMEI-borderland (SMEB) with mutations in the sodium channel alpha 1 subunit gene SCN1A is well established. To explore the phenotypic variability associated with SCN1A mutations, 188 patients with a range of epileptic encephalopathies were examined for SCN1A sequence variations by denaturing high performance liquid chromatography and sequencing. All patients had seizure onset within the first 2 years of life. A higher proportion of mutations were identified in patients with SMEI (52/66; 79%) compared to patients with SMEB (25/36; 69%). By studying a broader spectrum of infantile epileptic encephalopathies, we identified mutations in other syndromes including cryptogenic generalized epilepsy (24%) and cryptogenic focal epilepsy (22%). Within the latter group, a distinctive subgroup designated as severe infantile multifocal epilepsy had SCN1A mutations in three of five cases. This phenotype is characterized by early onset multifocal seizures and later cognitive decline. Knowledge of an expanded spectrum of epileptic encephalopathies associated with SCN1A mutations allows earlier diagnostic confirmation for children with these devastating disorders.
婴儿严重肌阵挛性癫痫（SMEI或Dravet综合征）与相关的钠通道α1亚基基因SCN1A突变的SMEI边缘综合征（SMEB）之间的关系已得到充分证实。为了探索与SCN1A突变相关的表型变异性，通过变性高效液相色谱法和测序对188例患有一系列癫痫性脑病的患者进行了SCN1A序列变异检测。所有患者均在生命的前2年内发病。与SMEB患者（25/36；69%）相比，SMEI患者中发现的突变比例更高（52/66；79%）。通过研究更广泛的婴儿癫痫性脑病谱，我们在其他综合征中发现了突变，包括隐源性全身性癫痫（24%）和隐源性局灶性癫痫（22%）。在后一组中，一个被指定为严重婴儿多灶性癫痫的独特亚组在五例中有三例存在SCN1A突变。这种表型的特征是早期发作的多灶性癫痫发作和后期的认知能力下降。了解与SCN1A突变相关的癫痫性脑病谱的扩展，有助于对患有这些严重疾病的儿童进行早期诊断确认。
