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. 1. Sudden Infant Death Syndrome Unlike other syndromes, the diagnosis of the sudden infant death syndrome (SIDS) is one of exclusion. Another particular feature of the syndrome is that all of its carriers are dead at the time of diagnosis. Not surprisingly, SIDS does not have a clear-cut pathophysiology. A large number of pathophysiological mechanisms have been suggested and investigated, including uncontrolled inflammatory responses, serotonergic abnormalities, and metabolic disorders. Presumably, SIDS is a multifactorial disorder, with several intrinsic and extrinsic factors resulting in or predisposing to its development, as proposed in the “triple risk model.” In the present section, I will present and discuss the various definitions of SIDS, its prevalence, common risk factors, the triple risk model, and some noncardiac genetic predispositions. 1.1. Definition The sudden and unexplained death of an apparently healthy infant is a tragic event. Typically, the infant is routinely put to sleep and found dead when one of the parents takes a look, which may be the next morning after having put the infant to sleep for the night or only minutes after having put the infant to sleep for a nap in the morning or afternoon. For such death, commonly known as
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