BackgroundSudden cardiac arrest is the leading mode of death in the United States. Epilepsy affects 1% of Americans; yet epidemiological data show a prevalence of 4% in cases of sudden cardiac arrest. Sudden unexpected death in epilepsy (SUDEP) may share features with sudden cardiac arrest. The objective of this study was to report autopsy and genomic findings in a large cohort of SUDEP cases.Methods and ResultsMayo Clinic Sudden Death Registry containing cases (ages 0–90 years) of sudden unexpected and unexplained deaths 1960 to present was queried. Exome sequencing performed on decedent cases. From 13 687 cases of sudden death, 656 (4.8%) had a history of seizures, including 368 confirmed by electroencephalography, 96 classified as SUDEP, 58 as non‐SUDEP, and 214 as unknown (insufficient records). Mean age of death in SUDEP was 37 (±19.7) years; 56 (58.3%) were male; 65% of deaths occurred at night; 54% were found in bed; and 80.6% were prone. Autopsies were obtained in 83 cases; bystander coronary artery disease was frequently reported as cause of death; nonspecific fibrosis was seen in 32.6% of cases, in structurally normal hearts. There were 4 cases of Dravet syndrome with pathogenic variants in SCN1A gene. Using whole exome sequencing in 11 cases, 18 ultrarare nonsynonymous variants were identified in 6 cases including CACNB2, RYR2, CLNB, CACNA1H, and CLCN2.ConclusionsThis study examined one of the largest single‐center US series of SUDEP cases. Several cases were reclassified as SUDEP, 15% had an ECG when alive, and 11 (11.4%) had blood for whole exome sequencing analysis. The most frequent antemortem genetic finding was pathogenic variants in SCN1A; postmortem whole exome sequencing identified 18 ultrarare variants.

中文翻译：

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通过全面尸检和全外显子组分子测序确认癫痫和意外死亡患者的死因


背景心脏骤停是美国主要的死亡方式。 1% 的美国人患有癫痫症；然而流行病学数据显示，心脏骤停病例的患病率为 4%。癫痫猝死（SUDEP）可能与心脏骤停具有相同的特征。本研究的目的是报告大量 SUDEP 病例的尸检和基因组发现。方法和结果梅奥诊所猝死登记处包含 1960 年至今的突然意外和不明原因死亡病例（年龄 0-90 岁）。对死者病例进行外显子组测序。 13 687例猝死病例中，656例（4.8%）有癫痫病史，其中脑电图确诊368例，SUDEP 96例，非SUDEP 58例，未知（记录不足）214例。 SUDEP 的平均死亡年龄为 37 (±19.7) 岁； 56 名（58.3%）为男性； 65%的死亡发生在夜间； 54%被发现躺在床上； 80.6%的人有倾向。对83例进行了尸检；旁观者冠状动脉疾病经常被报告为死亡原因；在结构正常的心脏中，32.6% 的病例出现非特异性纤维化。 Dravet综合征4例存在SCN1A基因致病性变异。通过对 11 例病例进行全外显子组测序，在 6 例病例中鉴定出 18 个极其罕见的非同义变异，包括CACNB2、RYR2、CLNB、CACNA1H和CLCN2 。结论本研究检查了美国最大的单中心 SUDEP 病例系列之一。一些病例被重新分类为 SUDEP，15% 的病例在活着时进行了心电图检查，11 例 (11.4%) 进行了血液用于全外显子组测序分析。 最常见的生前遗传学发现是SCN1A的致病性变异；死后全外显子组测序鉴定出 18 个极其罕见的变异。