Lee So, Karp Natalya, Zapata-Aldana Eugenio, Sadikovic Bekim, Yang Ping, Balci Tugce B, Prasad Asuri N
Division of Pediatric Neurology, Western University, London, Ontario, Canada.
Division of Genetics, Western University, London, Ontario, Canada.
Can J Neurol Sci. 2021 Mar;48(2):233-244. doi: 10.1017/cjn.2020.167. Epub 2020 Aug 3.
Retrospective observational study to determine diagnostic yield and utility of genetic testing in children with epilepsy attending the Epilepsy Clinic at Children's Hospital, London, Ontario, Canada.
Children (birth-18 years) with epilepsy, who were seen in a 10-year period (January 1, 2008-March 31, 2018), were selected using defined inclusion criteria and by combining clinic datasets and laboratory records.
In total, 105 children (52.38% male and 47.61% female) with a variety of seizures were included in the analysis. Developmental delay was documented in the majority (83; 79.04%). Overall, a genetic diagnosis was established in 24 (22.85%) children. The diagnostic yield was highest for whole-exome sequencing (WES), at 35.71%. The yield from microarray was 8.33%. Yields of single-gene testing (18.60%) and targeted multigene panel testing (19.23%) were very similar. Several likely pathogenic and pathogenic variants not previously reported were identified and categorized using ACMG criteria. All diagnosed patients underwent a review of anti-seizure medication management and received counseling on natural history of their disease, possible complications, recurrence risks, and possibilities of preimplantation or prenatal genetic diagnosis.
Our study confirms the multiple benefits of detecting a genetic etiology in children with epilepsy. Similar yields in single versus multigene testing underscore the importance of accurate clinical phenotyping. Patients with epilepsy and their caregivers in Ontario would undoubtedly benefit from repatriation of multigene panels and WES to the province.
一项回顾性观察研究，旨在确定加拿大安大略省伦敦市儿童医院癫痫门诊中癫痫患儿基因检测的诊断率及效用。
选取2008年1月1日至2018年3月31日这10年间就诊的癫痫患儿（出生至18岁），采用明确的纳入标准，并结合临床数据集和实验室记录。
总计105名患有各种癫痫发作类型的儿童（男性占52.38%，女性占47.61%）纳入分析。大多数患儿（83名；79.04%）有发育迟缓记录。总体而言，24名（22.85%）儿童确诊为遗传性癫痫。全外显子测序（WES）的诊断率最高，为35.71%。基因芯片的诊断率为8.33%。单基因检测（18.60%）和靶向多基因panel检测（19.23%）的诊断率非常相似。使用美国医学遗传学与基因组学学会（ACMG）标准鉴定并分类了几个此前未报告的可能致病和致病变异。所有确诊患者均接受了抗癫痫药物管理的评估，并就其疾病的自然史、可能的并发症、复发风险以及植入前或产前基因诊断的可能性接受了咨询。
我们的研究证实了检测癫痫患儿遗传病因的多重益处。单基因检测与多基因检测相似的诊断率凸显了准确临床表型分析的重要性。安大略省的癫痫患者及其护理人员无疑将从多基因panel和WES检测回归该省中受益。
