Department of Neurology, Children's Hospital of Chongqing Medical University, No. 136, Zhongshan Er Road, Yuzhong District, Chongqing, 400014, China.
Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 400014, China.
J Neurol. 2019 Sep;266(9):2224-2232. doi: 10.1007/s00415-019-09404-y. Epub 2019 May 31.
To study the phenotype, genotype, treatment strategies, and short-term prognosis of Chinese children with KCNQ2 (potassium voltage-gated channel subfamily Q member 2) related early-onset epileptic encephalopathies (KCNQ2-EOEEs) in Southwest China.
We used targeted next-generation sequencing (NGS) to identify KCNQ2 variants in Chinese patients with EOEEs. And patients with KCNQ2-EOEEs were confirmed after clinical and genetic analyses. We followed them in our cohort and analyzed their clinical data.
122 patients with EOEEs were registered from August 2015 to October 2017, and 78 underwent targeted NGS. Seven among them were confirmed to be caused by pathogenic KCNQ2 variants, 6 of that were de novo and 1 was inherited. The median seizure onset age of the 7 patients was 5 days. Tonic-clonic and tonic seizures were the major seizure types; the electroencephalograms of all patients showed multifocal sharp waves initially. When new seizure types appeared in infancy, the most common type was epileptic spasm. At the last follow-up, seizures persisted in only one patient, and another patient had seizure recurrence. The identified pathogenic KCNQ2 variants introduced amino acid missense changes, or in one instance, frameshift variant, four of which have not been reported. Valproic acid (VPA) was effective as concomitant treatment in three patients, and all patients had intellectual/developmental disabilities (IDDs).
The KCNQ2 missense variant plays an important role in EOEE pathogenesis, and patients with KCNQ2-EOEEs mainly present with intractable seizures and IDDs. Moreover, VPA has potential as an effective therapeutic strategy.
研究中国西南地区 KCNQ2（钾电压门控通道亚家族 Q 成员 2）相关早发性癫痫脑病（KCNQ2-EOEE）患儿的表型、基因型、治疗策略及短期预后。
我们采用靶向下一代测序（NGS）对早发性癫痫脑病患儿进行 KCNQ2 变异检测。经临床和遗传学分析，最终确诊为 KCNQ2-EOEE。对该队列中的患者进行随访，分析其临床资料。
2015 年 8 月至 2017 年 10 月共登记了 122 例早发性癫痫脑病患儿，其中 78 例行靶向 NGS。7 例患儿被证实为致病性 KCNQ2 变异所致，其中 6 例为新生突变，1 例为遗传突变。7 例患儿的中位起病年龄为 5 天。强直-阵挛和强直发作是主要的发作类型；所有患者的脑电图最初均显示多灶性棘波。当婴儿期出现新的发作类型时，最常见的类型是癫痫痉挛。末次随访时，仅 1 例患儿仍有发作，另 1 例患儿发作复发。鉴定的致病性 KCNQ2 变异导致氨基酸错义改变，其中 1 例为移码变异，这 4 种变异均未见报道。3 例患者同时应用丙戊酸（VPA）治疗有效，所有患者均存在智力/发育障碍（IDDs）。
KCNQ2 错义变异在 EOEE 发病机制中起重要作用，KCNQ2-EOEE 患儿主要表现为难治性癫痫和 IDDs。此外，VPA 可能是一种有效的治疗策略。
