Objective: To investigate the clinical and genetic characteristics of epilepsy associated with chromosome 16p11.2 microdeletion. Methods: The patients (n=10) with 16p11.2 microdeletion found in children with epilepsy treated in Beijing Children's Hospital Affiliated to Capital Medical University from January 2018 to January 2021 were collected. The clinical manifestations, gene variations and prognosis were analyzed retrospectively. Results: A total of 10 children's data were collected, including 5 male and 5 female. The onset age of epilepsy was 4.5 (4.1,5.0) months. Regarding the seizure types, 7 cases had focal seizures with secondary generalization, 2 cases had generalized seizures, and 1 case had tonic seizures and spasms. Nine cases had cluster seizure attacks and 3 cases had status epilepticus. Seven cases had focal or multifocal epileptiform discharges in interictal electroencephalogram (EEG), 3 cases had borderline or normal EEG. Brain magnetic resonance imaging showed polymicrogyria in 1 case, paraventricular leukomalacia in 1 case, delayed myelination of white matter in 3 cases, and no obvious abnormalities in the other 5 cases. The patients were followed up for 0.5-3.5 years, with 1-3 kinds of antiepileptic drugs taken orally. The case with polymicrogyria still had seizures, however the other 9 cases had seizures controlled. The age of the last seizure attack was 8 (6, 12) months. There were 6 cases with mental and motor developmental delay before epilepsy onset. During the follow-up, 7 cases were retarded to varying degrees, while 3 cases had normal development. Regarding the genetic detection methods, 7 cases underwent whole exome sequencing, 2 cases underwent whole genome copy number variation detection, and 1 case underwent whole genome sequencing. The length of the 16p11.2 deletion in 10 cases ranged from 525 to 951 kb, and all contained the PRRT2 gene intact. Six cases were de novo variants, 1 case was inherited from the mother who had a history of convulsions in early childhood, and the source of variant was not verified in 3 cases, none of whose parents had relevant phenotype. Conclusions: The epilepsy associated with 16p11.2 microdeletion is mainly induced by the heterozygous deletion of PRRT2 gene in this region, however the phenotype is usually severe, and often combined with developmental and epileptic encephalopathy. Detection of copy number variation should be emphasized in children whose etiology is considered genetic but second-generation sequencing result is negative.
目的： 探讨染色体16p11.2微缺失相关癫痫的临床及遗传学特点。 方法： 收集首都医科大学附属北京儿童医院2018年1月至2021年1月收治的癫痫患儿中发现16p11.2微缺失者10例的病例资料，回顾性总结分析其临床表现、基因变异情况、随访情况及预后。 结果： 10例患儿中男5例、女5例，癫痫起病年龄为4.5（4.1，5.0）月龄。癫痫发作类型中，7例为局灶性发作伴泛化，2例为全面性发作，1例为强直发作及痉挛发作。9例发作有丛集性，3例发生癫痫持续状态。脑电图发作间期7例为局灶或多灶性癫痫样放电，3例为界线性或无明显异常。头颅磁共振成像1例多小脑回畸形，1例侧脑室旁白质软化，3例脑白质髓鞘化延迟，余5例脑实质无明显异常。随访0.5~3.5年，患儿口服1~3种抗癫痫药物。存在脑发育畸形的1例仍有抽搐，余9例发作控制，末次发作的年龄为8（6，12）月龄。6例癫痫发病前即存在智力、运动发育落后，随访中7例不同程度发育落后，3例发育正常。7例患儿行全外显子组测序，2例行全基因组拷贝数变异检测，1例行全基因组测序；10例患儿的16p11.2缺失长度为525~951 kb不等，均完整包含PRRT2基因；6例为新生变异，1例遗传自母亲，其母幼儿期有抽搐史，3例未验证变异来源，其父母均无相关表型。 结论： 16p11.2微缺失相关癫痫与该区域的PRRT2基因杂合缺失有关，表型较重，常存在发育性癫痫性脑病。对于病因考虑遗传性因素但二代测序结果阴性的患儿，应重视拷贝数变异的检测。.