Division of Child Neurology, Department of Pediatric and Adolescent Medicine, American University of Beirut Medical Center, Riad El Solh, Beirut P.O. Box 11-0236, Lebanon.
Division of Child Neurology, Department of Neurology, Indiana University School of Medicine, Riley Hospital for Children, Indianapolis, IN 46202, USA.
Int J Mol Sci. 2024 Sep 6;25(17):9645. doi: 10.3390/ijms25179645.
Advances in genetics led to the identification of hundreds of epilepsy-related genes, some of which are treatable with etiology-specific interventions. However, the diagnostic yield of next-generation sequencing (NGS) in unexplained epilepsy is highly variable (10-50%). We sought to determine the diagnostic yield and clinical utility of NGS in children with unexplained epilepsy that is accompanied by neurodevelopmental delays and/or is medically intractable. A 5-year retrospective review was conducted at the American University of Beirut Medical Center to identify children who underwent whole exome sequencing (WES) or whole genome sequencing (WGS). Data on patient demographics, neurodevelopment, seizures, and treatments were collected. Forty-nine children underwent NGS with an overall diagnostic rate of 68.9% (27/38 for WES, and 4/7 for WGS). Most children (42) had neurodevelopmental delays with (18) or without (24) refractory epilepsy, and only three had refractory epilepsy without delays. The diagnostic yield was 77.8% in consanguineous families (18), and 61.5% in non-consanguineous families (26); consanguinity information was not available for one family. Genetic test results led to anti-seizure medication optimization or dietary therapies in six children, with subsequent improvements in seizure control and neurodevelopmental trajectories. Not only is the diagnostic rate of NGS high in children with unexplained epilepsy and neurodevelopmental delays, but also genetic testing in this population may often lead to potentially life-altering interventions.
遗传学的进步导致了数百个与癫痫相关的基因的鉴定，其中一些可以通过针对病因的干预措施进行治疗。然而，下一代测序（NGS）在不明原因癫痫中的诊断率差异很大（10-50%）。我们旨在确定 NGS 在伴有神经发育迟缓且/或药物难治性的不明原因癫痫儿童中的诊断率和临床应用价值。在美国贝鲁特大学医学中心进行了一项为期 5 年的回顾性研究，以确定接受全外显子组测序（WES）或全基因组测序（WGS）的儿童。收集了患者人口统计学、神经发育、癫痫发作和治疗的数据。49 名儿童接受了 NGS 检测，总体诊断率为 68.9%（WES 为 27/38，WGS 为 4/7）。大多数儿童（42 名）有神经发育迟缓，伴有（18 名）或不伴有（24 名）药物难治性癫痫，只有 3 名儿童仅有药物难治性癫痫而无神经发育迟缓。在近亲家庭（18 名）中的诊断率为 77.8%，在非近亲家庭（26 名）中的诊断率为 61.5%；有一个家庭的近亲信息不可用。基因检测结果导致 6 名儿童优化了抗癫痫药物或饮食疗法，随后癫痫发作得到控制，神经发育轨迹也得到改善。不仅是在伴有神经发育迟缓的不明原因癫痫儿童中 NGS 的诊断率较高，而且在该人群中进行基因检测通常也可以导致潜在改变生活的干预措施。
