KCNQ2突变相关婴幼儿癫痫的临床及遗传学分析

Clinical and genetic analysis of Chinese patients with KCNQ2 mutation-induced neonatal/infantile epileptic disorders

目的揭示KCNQ2突变相关婴幼儿癫痫的临床及遗传学特点,为KCNQ2突变相关婴幼儿癫痫患者的治疗选择及预后评估提供有益线索。方法收集2007年4月至2016年7月就诊于北京大学第一医院儿科的22例KCNQ2突变相关婴幼儿癫痫患者的临床资料,并结合靶向二代测序数据研究患儿的临床表型和基因型。结果22例患者中发现了KCNQ2新发错义突变。22例患儿的起病年龄中位数为出生后2 d,首次癫痫发作形式多为局灶性发作。在KCNQ2突变相关婴幼儿癫痫患儿中发现了一种新的发作形式,即不典型失神癫痫发作。本研究中的KCNQ2突变相关婴幼儿癫痫患者的病死率较高,22例患儿中有5例死亡,其中4例考虑为癫痫猝死。22例患儿中有8例仅用单药治疗后未再观察到临床发作,其中3例在应用丙戊酸治疗后未再观察到临床发作。结论本研究丰富了KCNQ2突变相关婴幼儿癫痫的临床表型;揭示了KCNQ2突变相关婴幼儿癫痫患者存在较高的病死率;提示丙戊酸可能是单药治疗KCNQ2突变相关婴幼儿癫痫的推荐选择之一。

Objective To reveal the clinical and genetic features of neonatal/infantile epileptic disorders caused by KCNQ2 mutations and to provide a clue for the treatment and prognosis evaluation. Methods Twenty-two patients were collected in the Department of Pediatrics, Peking University First Hospital from April 2007 to July 2016.The phenotype-genotype analysis was conducted of the neonatal/infantile epileptic patients in whom a KCNQ2 mutation was identified by the targeted next generation sequencing. Results Twenty-two de novo KCNQ2 missense mutations from 22 patients with neonatal/infantile epileptic disorders were found.These patients had an onset of epilepsy in early infancy (median age: 2 days). The seizure type of the first onset was mainly focal seizure.Atypical absence epilepsy, a novel phenotype of KCNQ2 mutation-induced epilepsies was found.The mortality of these patients was high, as 5 patients of the 22 patients died in the follow-up period, 4 of which might result from sudden unexpected death in epilepsy.In the 22 patients, 8 patients with anti-epileptic monotherapy became seizure-free.Of the 8 patients with a monotherapy, 3 patients were treated with valproic acid and no clinical onset was observed. Conclusions This study expands the phenotype of KCNQ2-related epileptic disorders.These patients have high mortality.Valproate acid is the potentially effective monotherapy for these patients.