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 MRI 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.

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摘要： 目的　总结及分析5例 CACNA1A 基因突变致发育性癫痫性脑病患儿的临床特点、基因突变特征及基因与表型之间的关联，为该病的早期诊断、治疗策略选择及遗传咨询提供依据。方法　收集河北省儿童医院神经内科建院（1989年）以来至2023年1月收治的5例 CACNA1A 基因突变致发育性癫痫性脑病患儿的临床资料、基因结果及家系验证。描述性分析患儿的临床特征、基因突变类型等。结果　5例发育性癫痫性脑病患儿中男3例、女2例，起病年龄2月龄至6岁8月龄。2例为遗传学变异，3例为新生变异。错义变异4例、无义变异1例。首次癫痫发作类型多样，其中3例为全面强直 - 阵挛发作、1例为局灶性发作、1例为失神发作，其中全面强直—阵挛发作、癫痫持续状态合并急性脑病1例。4例有全面发育落后、1例发育正常。视频脑电图可见广泛性棘慢波夹杂慢波1例、前头部尖波1例、多灶性棘波1例、广泛性棘波夹杂慢波1例、正常1例。头颅核磁可见正常3例，髓鞘化不良及额颞脑外间隙稍宽1例，局灶性髓鞘化不良、双额颞脑外间隙增宽、小脑脑沟增宽及双侧海马肿胀1例。随访1年，2例癫痫发作缓解，3例仍有间断发作。突变位点位于 Cav2.1钙通道的Ⅰ -S1区及Ⅳ -S6区羧基端表型严重，而位于Ⅳ -S6区及Ⅲ -S2区表型温和。经软件预测，表型严重，诊断为药物难治性癫痫患儿所携带的突变，均造成了蛋白结构改变；相反，表型温和患儿携带突变未引起蛋白质结构改变。结论　CACNA1A 变异导致的发育性癫痫性脑病发病年龄可从婴儿至学龄期起病，常见发作类型多样，大多为难治性癫痫，严重者可致癫痫持续状态及急性脑病，癫痫发作药物难治性可能与基因突变所在区域及其所带来的蛋白质结构改变有关。

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