Tashkandi Mariam, Baarma Duaa, Tricco Andrea C, Boelman Cyrus, Alkhater Reem, Minassian Berge A
Program in Genetics and Genome Biology, The Hospital for Sick Children, Institute of Medical Science, University of Toronto, Toronto.
Paediatric Neurology Division, Department of Paediatrics, King Abdullah Specialist Children Hospital, Riyadh.
Epileptic Disord. 2019 Feb 1;21(1):30-41. doi: 10.1684/epd.2019.1024.
Rolandic (RE), childhood absence (CAE) and juvenile myoclonic (JME) epilepsy encompass centrotemporal sharp waves, 3-Hz spike waves and >3-Hz spike or polyspike waves, respectively. Evidence abounds for genetic roles in all three syndromes, yet involved genes for the vast majority of patients remain unknown. It has long been proposed that while each disease is genetically complex, its specific EEG trait may represent a genetically simpler endophenotype. This meta-analysis of the literature focuses on the frequency of EEG traits in clinically unaffected first-degree relatives towards determining inheritance patterns of the EEG endophenotypes. We used the Preferred Reporting Items for Systematic Review and Meta-Analysis for protocols (PRISMA-P) and searched Medline, EMBASE, CINHAL and the Cochrane Central Register of Controlled Trials. Following extensive screening, 15 studies were included with a total of 3,858 asymptomatic relatives. The prevalence of 'abnormal' EEG waves was 21%, 42% and 33% for JME, CAE and RE, respectively, close to what would be expected based on Mendelian inheritance. However, breaking down the reported EEG abnormalities, most consisted not of the respective EEG signature traits -prevalences of which were as low as 5%- but of non-specific EEG 'abnormalities'/variants. Prevalence of non-specific EEG 'abnormalities'/variants in the general population ranges from 0.1 to 10%. Underlying this 100-fold-wide range is a spectrum of what is considered 'abnormal' or variant. The prevalences of 'abnormalities'/variants in asymptomatic siblings in RE, CAE and JME significantly exceed even the highest value in the general population and fall within Mendelian expectations. These results suggest that EEG 'abnormalities'/variants shared with the general population are enriched in the three syndromes and are endophenotypes inherited in a genetically simple near-Mendelian fashion. Future work with modern EEG variant definitions should uncover genetic variants contributing to neuronal hypersynchrony in epilepsy.
罗兰多癫痫（RE）、儿童失神癫痫（CAE）和青少年肌阵挛癫痫（JME）分别包含中央颞区尖波、3赫兹棘波和大于3赫兹的棘波或多棘波。有大量证据表明基因在这三种综合征中都发挥作用，但绝大多数患者的相关基因仍不明确。长期以来，人们一直认为，虽然每种疾病在遗传上都很复杂，但其特定的脑电图特征可能代表一种遗传上更简单的内表型。这项文献荟萃分析聚焦于临床未受影响的一级亲属中脑电图特征的频率，以确定脑电图内表型的遗传模式。我们使用系统评价和荟萃分析的首选报告项目（PRISMA-P），并检索了医学文献数据库（Medline）、荷兰医学文摘数据库（EMBASE）、护理学与健康领域数据库（CINHAL）以及考科蓝对照试验中心注册库。经过广泛筛选，纳入了15项研究，共有3858名无症状亲属。JME、CAE和RE的“异常”脑电图波的患病率分别为21%、42%和33%，接近基于孟德尔遗传预期的结果。然而，对报告的脑电图异常进行分类后发现，大多数并非各自的脑电图特征性波形——其患病率低至5%——而是非特异性的脑电图“异常”/变异。普通人群中非特异性脑电图“异常”/变异的患病率在0.1%至10%之间。在这个100倍的广泛范围内，存在一系列被认为是“异常”或变异的情况。RE、CAE和JME中无症状同胞的“异常”/变异患病率甚至显著超过普通人群中的最高值，且符合孟德尔预期。这些结果表明，与普通人群共有的脑电图“异常”/变异在这三种综合征中更为常见，并且是以遗传上简单的近孟德尔方式遗传的内表型。未来采用现代脑电图变异定义的研究应能发现导致癫痫中神经元过度同步的遗传变异。
