Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation
Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation
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DOI：
10.1111/epi.12200
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发表时间：
2013-07-01
期刊：
影响因子：
5.6
通讯作者：
Saitsu, Hirotomo
中科院分区：
文献类型：
--
作者：
Kato, Mitsuhiro;Yamagata, Takanori;Saitsu, Hirotomo
目的：在良性家族性新生儿癫痫发作、肌震颤或早发性癫痫性脑病（EOEE）患者中发现了KCNQ 2突变。方法：对239例EOEE患者（包括51例Ohtahara综合征和104例West综合征）进行高分辨率熔解（HRM）分析或全外显子组测序，并对KCNQ 2基因突变的临床特征进行分析。详细的临床资料，包括脑电图（EEG）和脑磁共振成像（MRI）收集与KCNQ 2突变的患者。关键发现：共9个新发和遗传突变被确定（两个突变复发发生）。所有12例患者的初始发作均发生在新生儿早期，主要为强直性发作。大多数患者脑电图呈抑制爆发型。仅3例患者EEG显示高度心律失常; 8例患者在接受卡马西平、唑尼沙胺、苯妥英、托吡酯或丙戊酸治疗后无癫痫发作。虽然癫痫发作得到了较好的控制，但除1例患者在3个月时死亡外，所有患者均出现了中度至重度的智力残疾。意义：EOEE中涉及到KCNQ 2的从头突变，其中大多数病例被诊断为Ohtahara综合征。这些病例表现出明显的特征，新生儿早期发病，强直性癫痫发作，抑制-爆发脑电图模式，罕见的发展为韦斯特综合征，对钠通道阻滞剂反应良好，但发育预后不良。EOEE患者应考虑进行KCNQ 2基因检测。
Purpose: KCNQ2 mutations have been found in patients with benign familial neonatal seizures, myokymia, or early onset epileptic encephalopathy (EOEE). In this study, we aimed to delineate the clinical spectrum of EOEE associated with KCNQ2 mutation.Methods: A total of 239 patients with EOEE, including 51 cases with Ohtahara syndrome and 104 cases with West syndrome, were analyzed by high-resolution melting (HRM) analysis or whole-exome sequencing. Detailed clinical information including electroencephalography (EEG) and brain magnetic resonance imaging (MRI) were collected from patients with KCNQ2 mutation.Key Findings: A total of nine de novo and one inherited mutations were identified (two mutations occurred recurrently). The initial seizures, which were mainly tonic seizures, occurred in the early neonatal period in all 12 patients. A suppression-burst pattern on EEG was found in most. Only three patients showed hypsarrhythmia on EEG; eight patients became seizure free when treated with carbamazepine, zonisamide, phenytoin, topiramate, or valproic acid. Although the seizures were relatively well controlled, moderate-to-profound intellectual disability was found in all except one patient who died at 3 months.Significance: De novo KCNQ2 mutations are involved in EOEE, most of which cases were diagnosed as Ohtahara syndrome. These cases showed distinct features with early neonatal onset, tonic seizures, a suppression-burst EEG pattern, infrequent evolution to West syndrome, and good response to sodium channel blockers, but poor developmental prognosis. Genetic testing for KCNQ2 should be considered for patients with EOEE.