66例不明原因智力障碍/发育迟缓儿童临床和遗传学分析

目的 探讨不明原因智力障碍/发育迟缓(ID/DD)患儿的临床资料及基因检测结果,为进行明确的病因学诊断、评估患者预后提供遗传学咨询。 方法 收集不明原因ID/DD患儿66例,总结分析患儿的智力测评、神经影像学及视频脑电图检查结果等,选择遗传学检测技术包括染色体微阵列分析(CMA)、全外显子组基因测序(WES),明确致病性拷贝数变异及基因突变位点。 结果(1)66例患儿均表现为智力低下,对应年龄阶段发育里程碑事件明显延迟。(2)45例患儿发现遗传变异,检出率为68.2%,其中22例(33.3%)为致病性突变,病因诊断明确。(3)确诊Prader-Willi综合征4例; Williams-Beuren综合征3例; 15q部分三体综合征、智力障碍20型各2例; Angelman综合征、4q末端缺失综合征、Phelan-McDermid综合征、9p三体综合征、智力低下6型、Langer-Giedion 综合征、1p36缺失综合征及婴儿神经轴索营养不良各1例。 结论 CMA作为不明原因ID/DD或先天性畸形等疾病的首选检测技术,结合WES可为ID/DD的确诊提供较可靠的依据,尤其对临床症状和表型不具特异性患者的诊断有重要意义。

Clinical and Genetic Analysis of 66 Children with Unexplained Intellectual Disability/Developmental Delay

Objective To explore the clinical features and gene test results of 66 children with unexplained intellectual disability/developmental delay(ID/DD)for the purpose of providing clear etiological diagnosis, patient prognosis, and genetic counseling. Methods Clinical date, intelligence test, neuroimaging, and video electroencephalogram results were collected from the 66 ID/DD children. The genetic detection techniques including chromosome microarray analysis(CMA), and whole exome sequencing(WES)were selected to identify pathogenic copy number variation and gene mutation. Results(1)66 children with ID/DD all presented with mental retardation and significant delays in developmental milestone events.(2)The genetic variation was found in 45 children with ID/DD. The detection rate of genetic variation was 68.2%. 22 of them were pathogenic mutations, for which etiological diagnosis was clear. The diagnostic positive rate was 33.3%.(3)Confirmed 4 cases of Prader-Willi syndrome; 3 cases of Williams-Beuren syndrome; 2 cases of partial trisomy 15q and mental retardation syndrome 20; 1 case each of Angelman syndrome, 4q terminal deletion syndrome, Phelan-McDermid syndrome, 9p trisomy syndrome, mental retardation type 6, Langer-Giedion syndrome, 1p36 deletion syndrome, andinfant axonal malnutrition. Conclusions As the preferred detection technology for ID/DD and/or congenital malformation, CMA combined with WES can provide a reliable basis for the diagnosis, especially for those with no specific clinical symptoms and phenotypes.