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Abstract：
Background Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related death. SUDEP shares many features with sudden cardiac death and sudden unexplained death in the young and may have a similar genetic contribution. We aim to systematically review the literature on the genetics of SUDEP. Methods and Results PubMed, MEDLINE Epub Ahead of Print, Ovid Medline In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Scopus were searched through April 4, 2017. English language human studies analyzing SUDEP for known sudden death, ion channel and arrhythmia-related pathogenic variants, novel variant discovery, and copy number variant analyses were included. Aggregate descriptive statistics were generated; data were insufficient for meta-analysis. A total of 8 studies with 161 unique individuals were included; mean was age 29.0 (±SD 14.2) years; 61% males; ECG data were reported in 7.5% of cases; 50.7% were found prone and 58% of deaths were nocturnal. Cause included all types of epilepsy. Antemortem diagnosis of Dravet syndrome and autism (with duplication of chromosome 15) was associated with 11% and 9% of cases. The most frequently detected known pathogenic variants at postmortem were in Na+ and K+ ion channel subunits, as were novel potentially pathogenic variants (11%). Overall, the majority of variants were of unknown significance. Analysis of copy number variant was insignificant. Conclusions SUDEP case adjudication and evaluation remains limited largely because of crucial missing data such as ECGs. The most frequent pathogenic/likely pathogenic variants identified by molecular autopsy are in ion channel or arrhythmia-related genes, with an ≈11% discovery rate. Comprehensive postmortem examination should include examination of the heart and brain by specialized pathologists and blood storage.
摘要：
背景：癫痫突然意外死亡（SUDEP）是癫痫相关死亡的主要原因。SUDEP与年轻人的心脏猝死和无法解释的猝死具有许多特征，并且可能具有相似的遗传贡献。我们旨在系统地回顾有关SUDEP遗传学的文献。方法和结果PubMed，MEDLINEEpub在打印之前，OvidMedline正在进行中和其他非索引引文，MEDLINE,EMBASE,Cochrane系统评价数据库，和Scopus在2017年4月4日进行了搜索。英语语言人类研究分析SUDEP已知的猝死，离子通道和心律失常相关的致病变异，新的变体发现，并包括拷贝数变异分析。生成了总体描述性统计；数据不足以进行荟萃分析。共纳入8项研究，包括161名独特个体；平均年龄为29.0（±SD14.2）岁；61％的男性；在7.5％的病例中报告了ECG数据；50.7％的病例易发，58％的死亡是夜间死亡。原因包括所有类型的癫痫。Dravet综合征和自闭症（染色体15重复）的死前诊断与11％和9％的病例相关。在死后最常见的已知致病变异是在Na+和K+离子通道亚基，新的潜在致病变异(11%).总的来说,大多数变异具有未知的意义.拷贝数变异分析不显著。结论SUDEP案件的裁决和评估在很大程度上仍然受到限制，原因是关键的数据缺失，例如心电图。通过分子尸检确定的最常见的致病/可能的致病变异是在离子通道或心律失常相关基因中。发现率为约11%。全面的尸检应包括由专业病理学家检查心脏和大脑以及血液储存。
