以癫痫为主要表型的16p11.2微缺失综合征11例病例系列报告

背景：16p11.2微缺失综合征具有高度临床异质性，目前国内相关研究多为病例报告。目的：总结以癫为主要表型的16p11.2微缺失综合征患儿的临床特征，以提高对该病的认识。设计：病例系列报告。方法：纳入2017年7月至2021年10月深圳市儿童医院神经内科收治的癫患儿中确诊为16p11.2微缺失综合征者。从病历系统中截取患儿的临床表型、实验室检查结果，脑电图及神经心理评估结果，影像学检查报告，治疗和随访情况。遗传学检测：采集患儿及其父母的外周静脉血行基因检测。主要结局指标：临床表型和遗传学异常。结果：11例16p11.2微缺失综合征患儿进入本文分析，中位发病年龄7（3~36）月龄，男6例。首发症状均为抽搐，发作类型均为局灶性发作。语言迟缓8例，运动发育迟缓2例，其中1例出现发作性运动诱发性运动障碍（PKD）。8例脑电图见间期放电，3例背景正常或界限。1例颅脑MR见白质异常信号。11例基因检测均提示16p11.2微缺失（524~908 kb），8例为新发突变。缺失重叠区域chr16:29674991 30199601中包含27个编码蛋白的基因，其中6个为与疾病相关的OMIM基因，仅PRRT2基因有充足证据表明为单倍体剂量不足，该基因引起良性婴幼儿癫。11例癫均易控制。9例应用抗癫药物治疗，其中8例单用奥卡西平、丙戊酸钠或托吡酯；1例先后使用苯巴比妥和左乙拉西坦治疗，治愈并停药后出现PKD，使用奥卡西平治疗后未再发作。结论：16p11.2微缺失综合征是引起婴幼儿癫痫的原因之一，遗传评估中应予以关注。临床需对16p11.2微缺失综合征患儿行动态神经心理评估并关注PKD症状，以及时诊治。

11 cases of children with epilepsy caused by 16p11.2 deletion: A case series report

Background：The clinical spectrum of 16p11.2 microdeletion syndrome is highly heterogeneous, and most studies are case reports. Objective：To summarize the clinical features of 16p11.2 microdeletion syndrome with epilepsy as the main phenotype, so as to improve the clinical understanding of this disease. Design：Case series report. Methods：From July, 2017 to October, 2021, children with epilepsy diagnosed as 16p11.2 microdeletion syndrome in the Department of Neurology, Shenzhen Children's Hospital were included. The clinical manifestations, laboratory examination results, EEG and neuropsychological evaluation results, imaging examination reports, treatment and follow-up of children were intercepted from the medical record system. Peripheral venous blood was collected from patients and their parents for the genetic testing. Main outcome measures：Clinical phenotype and genetic abnormality analysis. Results：Totally 11 patients (age range: 3 36 months; median age: 7 months; male:6, female: 5), were enrolled. All 11 patients presented focal seizure as the early symptom. There are 8 cases of language retardation and 2 cases of motor retardation (including 1 case of paroxysmal motor induced dyskinesia). By EGG, 8 patients were found having intermittent discharge while the other 3 patients had normal EGG backgrounds, and by brain MR imaging, 1 case of abnormal white matter signal was observed. The 11 cases of 16p11.2 microdeletion showed a deletion of 524 908 kb and 8 of them were de novo mutations. The overlapping region chr16:29674991 30199601 contains 27 protein coding genes and 6 of them are disease related OMIM genes. Only PRRT2 was well evidenced to be haploinsufficient, which causes benign infantile epilepsy. Epilepsy was easy to control in all these patients. Nine cases were treated with antiepileptic drugs, including monotherapy of oxcarbazepine, sodium valproate or topiramate (n=8) and combination therapy of phenobarbital and levetiracetam (n=1). Paroxysmal motor induced dyskinesia occurred after the combination therapy cure the disease and was stopped, but it did not happen again after the oxcarbazepine treatment. Conclusion：16p11.2 microdeletion syndrome is one of the potential causes of epilepsy, which should be paid attention to in genetic evaluation. For children with 16p11. 2 microdeletion syndrome, dynamic neuropsychological evaluation is needed and attention should be paid to PKD symptoms so as to make timely diagnosis and treatment.