Ebach K, Joos H, Doose H, Stephani U, Kurlemann G, Fiedler B, Hahn A, Hauser E, Hundt K, Holthausen H, Müller U, Neubauer B A
Department of Neuropediatrics, University of Giessen, Giessen, Germany.
Neuropediatrics. 2005 Jun;36(3):210-3. doi: 10.1055/s-2005-865607.
Severe myoclonic epilepsy in infancy (SMEI), severe idiopathic generalized epilepsy of infancy (SIGEI) with generalized tonic clonic seizures (GTCS), and myoclonic astatic epilepsy (MAE) may show semiological overlaps. In GEFS+ families, all three phenotypes were found associated with mutations in the SCN1A gene. We analyzed the SCN1A gene in 20 patients with non-familial myoclonic astatic epilepsy -- including 12 probands of the original cohort used by Doose et al. in 1970 to delineate MAE. In addition, 18 patients with sporadic SIGEI -- mostly without myoclonic-astatic seizures -- were analyzed. Novel SCN1A mutations were found in 3 individuals. A frame shift resulting in an early premature stop codon in a now 35-year-old woman with a borderline phenotype of MAE and SIGEI (L433fsX449) was identified. A splice site variant (IVS18 + 5 G --> C) and a missense mutation in the conserved pore region (40736 C --> A; R946 S) were detected each in a child with SIGEI. We conclude that, independent of precise syndromic delineation, myoclonic-astatic seizures are not predictive of SCN1A mutations in sporadic myoclonic epilepsies of infancy and early childhood.
婴儿严重肌阵挛癫痫（SMEI）、伴有全身强直阵挛发作（GTCS）的婴儿严重特发性全身性癫痫（SIGEI）以及肌阵挛失张力癫痫（MAE）可能存在症状学重叠。在GEFS + 家系中，发现所有这三种表型均与SCN1A基因突变有关。我们分析了20例非家族性肌阵挛失张力癫痫患者的SCN1A基因，其中包括1970年Doose等人用于界定MAE的原始队列中的12名先证者。此外，还分析了18例散发性SIGEI患者，其中大多数无肌阵挛失张力发作。在3名个体中发现了新的SCN1A突变。在一名35岁具有MAE和SIGEI临界表型的女性中鉴定出一个移码突变，导致提前出现过早的终止密码子（L433fsX449）。在一名SIGEI患儿中分别检测到一个剪接位点变异（IVS18 + 5 G→C）和保守孔区的一个错义突变（40736 C→A；R946 S）。我们得出结论，独立于精确的综合征界定，在婴儿期和儿童早期的散发性肌阵挛癫痫中，肌阵挛失张力发作不能预测SCN1A突变。
