Cardiac channelopathies and sudden infant death syndrome

Sudden Infant Death Syndrome (SIDS) represents the leading cause of postneonatal sudden death in developed countries, the third leading cause of infant mortality overall in the United States, and a source of devastating psychosocial consequences for the families of victims. This chapter (i) describes the cardiac QT hypothesis for SIDS according to which some cases of SIDS might be due to ventricular fibrillation associated with prolonged repolarization, (ii) summarizes the results of an 18-year long prospective study with electrocardiogram (ECG) recordings in over 34,000 infants, (iii) discusses recent findings which provide the molecular and functional evidence linking SIDS to cardiac channelopathies like the congenital long QT syndrome (LQTS), Short QT syndrome (SQTS), Brugada syndrome (BrS), and catecholaminergic polymorphic ventricular tachycardia (CPVT), (iv) presents the results of a prospective ECG study involving 45,000 infants which provided the first opportunity for a data-driven assessment of the prevalence of LQTS and summarizes the main finding of a cost-effectiveness study which analyzes a screening neonatal ECG program in a large European country, and (v) addresses the implications of 35 plus years of research on LQTS and SIDS. The studies presented here provide the conclusive evidence that genetically mediated arrhythmias represent a significant and non-dismissible cause of SIDS and support the concept of widespread neonatal ECG screening for the identification of a subset of infants at high risk for sudden death that can be prevented as it is the case with most patients affected by LQTS.