CDKL 5缺乏症患儿的临床特征与遗传学分析

Clinical features and genetic analysis of children with CDKL 5 deficiency disorder

目的探讨CDKL 5缺乏症(CDD)患儿CDKL 5基因突变相关早发性癫痫脑病的临床表型特点。方法收集2018年11月至2023年1月经全外显子组测序技术筛选出的10例CDD CDKL 5基因突变患儿的临床资料,并进行临床表型及基因型分析。结果10例患儿中女性8例、男性2例,起病年龄为1~15月龄,中位年龄为2月龄。CDD患儿的癫痫发作包括痉挛发作、局灶性发作、强直发作及肌阵挛发作等。10例患儿经基因检测证实为CDKL 5基因变异,包括4例移码变异(c.1330delC、c.786delC、c.163_166del、c.2821delT)、4例无义突变(c.2277G>A、c.2249C>G、c.1648C>T、c.2854C>T)及2例错义突变(c.3068A>G、c.1819C>T),其中7个位点尚未被报道。结论CDD患儿CDKL 5基因突变起病早,发作形式多样,本研究对CDKL 5基因突变相关癫痫病例10例CDD患儿的临床特征及基因表现进行分析,丰富了CDKL 5基因突变相关癫痫的临床认识。

Objective To explore the clinical phenotypic characteristics of CDKL 5 gene mutation-associated early-onset epileptic encephalopathy in children with CDKL 5 deficiency disorder(CDD).Methods Clinical data was collected from 10 CDD children carrying CDKL 5 gene mutations screened by whole exome sequencing technology from November 2018 to January 2023.Clinical phenotypes and genotypes were analyzed.Results Among 10 patients,there were 8 females and 2 males,and their onset at age ranged from 1 month to 15 months,with a median age of 2 months.Epileptic seizures in children with CDD included spastic seizures,focal seizures,tonic seizures and myoclonic seizures.These 10 children were confirmed to carry genetic test-diagnosed CDKL 5 gene mutations,among which,4 patients with frameshift mutations(c.1330delC,c.786delC,c.163_166del,c.2821delT),4 patients with nonsense mutations(c.2277G>A,c.2249C>G,c.1648C>T,c.2854C>T)and 2 patients with missense mutations(c.3068A>G,c.1819C>T).Among these mutation loci,7 loci have not been reported before.Conclusion CDD Children carrying CDKL 5 gene mutation have early onsets and a variety of seizure forms.This study analyzed the clinical characteristics and genetic manifestations of 10 children with CDD related epilepsy caused by CDKL 5 gene mutations,enriching the clinical understanding of CDKL 5 gene mutation related epilepsy.