Angione Katie, Eschbach Krista, Smith Garnett, Joshi Charuta, Demarest Scott
University of Colorado Denver, Department of Pediatrics, Section of Neurology, United States.
University of Colorado Denver, Department of Pediatrics, Section of Neurology, United States.
Epilepsy Res. 2019 Feb;150:70-77. doi: 10.1016/j.eplepsyres.2019.01.008. Epub 2019 Jan 14.
Epilepsy with myoclonic-atonic seizures (EMAS) accounts for 1-2% of all childhood-onset epilepsies. EMAS has been shown to have an underlying genetic component, however the genetics of this disorder is not yet well understood. The purpose of this study was to review genetic testing results for a cohort of EMAS patients. A retrospective chart review was conducted for 77 patients evaluated at Children's Hospital Colorado with a potential diagnosis of EMAS. Genetic testing and biochemical testing was reviewed. Family history data was also collected. Seventy-seven percent of the cohort had at least one genetic test performed, and a molecular diagnosis was reached for six patients. Thirty-seven patients had a microarray, six of which identified a copy number variant. Only one was felt to contribute to the phenotype (2p16.3 deletion including NRXN1). Fifty-one patients had an epilepsy panel, two of which were positive (likely pathogenic variant in SCN1A, pathogenic variant in GABRG2). Of the six patients who had whole exome sequencing, two were negative, three were positive or likely positive, and one had multiple variants not felt to explain the phenotype. While EMAS is widely accepted to have a strong genetic component, the diagnostic yield of genetic testing remains low. This may be because several genes now thought to be associated with EMAS are not included on the more commonly ordered epilepsy panels, or have only recently been added to them.
肌阵挛失张力发作性癫痫（EMAS）占所有儿童期起病癫痫的1%-2%。已有研究表明EMAS存在潜在的遗传因素，然而该疾病的遗传学尚未完全明确。本研究的目的是回顾一组EMAS患者的基因检测结果。对科罗拉多儿童医院评估的77例疑似EMAS患者进行了回顾性病历审查。审查了基因检测和生化检测情况。还收集了家族史数据。该队列中77%的患者至少进行了一项基因检测，6例患者获得了分子诊断。37例患者进行了基因芯片检测，其中6例发现了拷贝数变异。仅1例被认为与表型有关（2p16.3缺失，包括NRXN1）。51例患者进行了癫痫基因检测板检测，其中2例呈阳性（SCN1A可能存在致病变异，GABRG2存在致病变异）。在6例进行了全外显子测序的患者中，2例为阴性，3例为阳性或可能为阳性，1例有多个变异但认为无法解释表型。虽然普遍认为EMAS有很强的遗传因素，但基因检测的诊断率仍然很低。这可能是因为目前认为与EMAS相关的几个基因未包含在更常用的癫痫基因检测板中，或者是最近才添加到其中。
