Early-Life Epilepsies and the Emerging Role of Genetic Testing
Early-Life Epilepsies and the Emerging Role of Genetic Testing
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DOI：
10.1001/jamapediatrics.2017.1743
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发表时间：
2017-09-01
期刊：
影响因子：
26.1
通讯作者：
Koh, Sookyong
中科院分区：
文献类型：
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作者：
Berg, Anne T.;Coryell, Jason;Koh, Sookyong
早期癫痫通常是许多神经发育障碍的结果，其中大多数被证明具有遗传起源。在这些癫痫的初始评估中基因检测的作用还没有建立。目的提供一个当代帐户的使用模式和诊断率的基因检测的早期生命epilepsies.DESIGN，设置，和参与者在这个前瞻性队列中，儿童与新诊断的癫痫发作小于3岁，从2012年3月1日，至4月30日，2015年，来自17家美国儿科医院，随访1年。在接触的795个家庭中，775个同意参加。癫痫病因学的临床诊断是基于进行基因检测之前的可用信息进行的。结果：在775名患者中（367名女孩和408名男孩;发病年龄中位数为7.5个月[四分位数间距为4.2-16.5个月]），95名（12.3%）有获得性脑损伤。其余680名患者中，327名（48.1%）接受了各种形式的基因检测，在327名儿童中发现了132例致病变异（40.4%; 95% CI，37%-44%）：26/59核型分析阳性率为44.1%，114例患者中有31例（27.2%）采用癫痫组检测，33例患者中有11例（33.3%）采用全外显子组检测，20例患者中有4例（20.0%）采用线粒体组检测，94例患者中有28例（29.8%）采用其他检测。在最初的癫痫表现之前确定了44个变体。除畸形综合征外，患有结节性硬化症（11例中的9例[81.8%]）、代谢性疾病（14例中的11例[78.6%]）和脑畸形（61例中的20例[32.8%]）的儿童的致病率最高。446名儿童中共有180名（40.4%）接受了一些检测，这些儿童的病因在没有基因检测的情况下仍然未知。在180名儿童中的48名中鉴定出致病性变体（26.7%; 95% CI，18%-34%）。诊断率大于15%，无论延迟，痉挛，和年轻。癫痫组的产率更高（96例中的28例[29.2%]; P
IMPORTANCE Early-life epilepsies are often a consequence of numerous neurodevelopmental disorders, most of which are proving to have genetic origins. The role of genetic testing in the initial evaluation of these epilepsies is not established.OBJECTIVE To provide a contemporary account of the patterns of use and diagnostic yield of genetic testing for early-life epilepsies.DESIGN, SETTING, AND PARTICIPANTS In this prospective cohort, children with newly diagnosed epilepsy with an onset at less than 3 years of age were recruited from March 1, 2012, to April 30, 2015, from 17 US pediatric hospitals and followed up for 1 year. Of 795 families approached, 775 agreed to participate. Clinical diagnosis of the etiology of epilepsy were characterized based on information available before genetic testing was performed. Added contributions of cytogenetic and gene sequencing investigations were determined.EXPOSURES Genetic diagnostic testing.MAIN OUTCOMES AND MEASURES Laboratory-confirmed pathogenic variant.RESULTS Of the 775 patients in the study (367 girls and 408 boys; median age of onset, 7.5 months [interquartile range, 4.2-16.5 months]), 95 (12.3%) had acquired brain injuries. Of the remaining 680 patients, 327 (48.1%) underwent various forms of genetic testing, which identified pathogenic variants in 132 of 327 children (40.4%; 95% CI, 37%-44%): 26 of 59 (44.1%) with karyotyping, 32 of 188 (17.0%) with microarrays, 31 of 114 (27.2%) with epilepsy panels, 11 of 33 (33.3%) with whole exomes, 4 of 20 (20.0%) with mitochondrial panels, and 28 of 94 (29.8%) with other tests. Forty-four variants were identified before initial epilepsy presentation. Apart from dysmorphic syndromes, pathogenic yields were highest for children with tuberous sclerosis complex (9 of 11 [81.8%]), metabolic diseases (11 of 14 [78.6%]), and brain malformations (20 of 61 [32.8%]). A total of 180 of 446 children (40.4%), whose etiology would have remained unknown without genetic testing, underwent some testing. Pathogenic variants were identified in 48 of 180 children (26.7%; 95% CI, 18%-34%). Diagnostic yields were greater than 15% regardless of delay, spasms, and young age. Yields were greater for epilepsy panels (28 of 96 [29.2%]; P