Wilders Ronald
Department of Anatomy, Embryology and Physiology, Heart Failure Research Center, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands.
ISRN Cardiol. 2012;2012:846171. doi: 10.5402/2012/846171. Epub 2012 Dec 5.
The sudden infant death syndrome (SIDS) causes the sudden death of an apparently healthy infant, which remains unexplained despite a thorough investigation, including the performance of a complete autopsy. The triple risk model for the pathogenesis of SIDS points to the coincidence of a vulnerable infant, a critical developmental period, and an exogenous stressor. Primary electrical diseases of the heart, which may cause lethal arrhythmias as a result of dysfunctioning cardiac ion channels ("cardiac ion channelopathies") and are not detectable during a standard postmortem examination, may create the vulnerable infant and thus contribute to SIDS. Evidence comes from clinical correlations between the long QT syndrome and SIDS as well as genetic analyses in cohorts of SIDS victims ("molecular autopsy"), which have revealed a large number of mutations in ion channel-related genes linked to inheritable arrhythmogenic syndromes, in particular the long QT syndrome, the short QT syndrome, the Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia. Combining data from population-based cohort studies, it can be concluded that at least one out of five SIDS victims carries a mutation in a cardiac ion channel-related gene and that the majority of these mutations are of a known malignant phenotype.
婴儿猝死综合征（SIDS）会导致看似健康的婴儿突然死亡，即便进行了全面调查，包括完整的尸检，死亡原因仍无法解释。SIDS发病机制的三重风险模型指出，脆弱的婴儿、关键的发育阶段和外部应激源同时出现会导致发病。心脏原发性电疾病可能因心脏离子通道功能异常（“心脏离子通道病”）而引发致命性心律失常，且在标准尸检中无法检测到，这类疾病可能造就了脆弱的婴儿，从而导致SIDS。证据来源于长QT综合征与SIDS之间的临床关联，以及对SIDS受害者队列的基因分析（“分子尸检”），这些分析揭示了与遗传性致心律失常综合征相关的离子通道相关基因中存在大量突变，尤其是长QT综合征、短QT综合征、Brugada综合征和儿茶酚胺能多形性室性心动过速。综合基于人群的队列研究数据，可以得出结论，至少五分之一的SIDS受害者携带心脏离子通道相关基因的突变，且这些突变中的大多数具有已知的恶性表型。
