The spectrum of SCNIA-related infantile epileptic encephalopathies
The spectrum of SCNIA-related infantile epileptic encephalopathies
复制标题
DOI：
10.1093/brain/awm002
复制
发表时间：
2007-03-01
期刊：
影响因子：
14.5
通讯作者：
Scheffer, Ingrid E.
中科院分区：
文献类型：
--
作者：
Harkin, Louise A.;McMahon, Jacinta M.;Scheffer, Ingrid E.
婴儿严重肌阵挛性癫痫（SMEI或Dravet综合征）与钠通道α 1亚单位基因SCN 1A突变相关的SMEI-边界综合征（SMEB）之间的关系已得到充分证实。为了探索与SCN 1A突变相关的表型变异，通过变性高效液相色谱和测序对188例患有一系列癫痫性脑病的患者进行了SCN 1A序列变异检查。所有患者均在出生后2年内发生癫痫发作。与SMEB患者（25/36; 69%）相比，SMEI患者（52/66; 79%）中发现的突变比例更高。通过研究更广泛的婴儿癫痫性脑病，我们确定了其他综合征的突变，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个病例中的三个中具有SCN 1A突变。这种表型的特征是早发性多灶性癫痫发作和后来的认知能力下降。与SCN 1A突变相关的癫痫性脑病的扩展谱的知识允许对患有这些破坏性疾病的儿童进行早期诊断确认。
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.