摘要
Abstract
Objective This study aims to summarize and analyze the clinical features,genetic mutation characteristics,and gene-phenotype correlations in five pediatric patients with developmental epileptic encephalopathy caused by CACNA1A gene mutations,in order to provide a basis for early diagnosis,treatment strategy selection,and genetic counseling of this condition.Methods Clinical data,genetic results,and family verification reports were collected in five pediatric patients with developmental epileptic encephalopathy caused by CACNA1A gene mutations admitted to the Department of Neurology of Hebei Children's Hospital from its establishment(1989)to January 2023.Descriptive analysis was conducted on the patients' clinical characteristics,mutation types,and other relevant factors.Results Among the 5 pediatric patients with developmental epileptic encephalopathy,3 were male and 2 were female,with onset ages ranging from 2 months to 6 years and 8 months.Two cases were inherited mutations,while 3 were de novo mutations.There were four cases of missense mutations and one case of nonsense mutation.The initial seizure types varied:three were generalized tonic-clonic seizures,one was a focal seizure,and one was an absence seizure.Among them,one case was a generalized tonic-clonic seizure with status epilepticus complicated by acute encephalopathy.Four patients exhibited generalized developmental delay,while one had normal development.Video EEG findings included 1 case of generalized spike-and-wave activity intermixed with slow waves,1 case of frontal spikes,1 case of multifocal spikes,1 case of generalized spike-and-wave activity intermixed with slow waves,and 1 normal case.Cranial MR1 showed that there were 3 normal cases,1 case of demyelination with mild widening of the frontal-temporal subarachnoid space,and 1 case of focal demyelination,bilateral widening of the frontal-temporal subarachnoid space,widening of cerebellar sulci,and bilateral hippocampal swelling.During the 1-year follow-up,seizures resolved in 2 patients while 3 patients continued to experience intermittent seizures.Mutations located in the Ⅰ-S1 and Ⅳ-S6 regions of the Cav2.1 calcium channel carboxyl-terminal domain resulted in severe phenotypes,whereas mutations in the Ⅳ-S6 and Ⅲ-S2 regions led to mild phenotypes.Software prediction indicated that mutations in children with severe phenotypes diagnosed with drug-resistant epilepsy caused structural alterations in the protein;on the contrary,mutations in children with mild phenotypes did not induce structural changes in the protein.Conclusion The age of onset of developmental epileptic encephalopathy caused by CACNA1A mutations ranges from infancy to school age.Common seizure types are diverse,with most cases presenting as drug-resistant epilepsy.Severe cases may lead to status epilepticus and acute encephalopathy.The drug-resistant nature of seizures may be related to the location of the gene mutation and the resulting structural alterations in the protein.关键词
CACNA1A基因突变/发育性癫痫性脑病/全外基因检测Key words
CACNA1A gene mutation/developmental epileptic encephalopathy/whole exome gene testing分类
医药卫生
