Update on the similarities between SADS, SIDS, and SUDEP: Three sides of the same pyramid?

Sudden Arrhythmic Death Syndrome (SADS), Sudden Unexpected Death In Epilepsy (SUDEP) and Sudden Infant Death Syndrome (SIDS) present some overlaps and similarities in terms of molecular autopsy and pathophysiological mechanism. Genes associated with cardiac arrhythmias represent promising biomarkers, in light of the growing evidence of neurocardiac interconnections and phenotypic similarities between SUDEP, SADS and also SIDS. The interactions between these different forms of sudden death are reciprocal and could help to understand the mechanism of death that in some cases remains unexplained. In this review of the literature we analyse the overlaps and the common aspects between these different conditions of sudden death, we discuss the clinical, social and medico-legal implications. SIDS, SADS and SUDEP still represent a huge challenge for the Forensic Pathologist and their diagnostic interpretation contains some ambiguities and evaluation difficulties. All cases of sudden death require a thorough cardio-pathological and neuropathological evaluation. A thorough anamnesis and molecular analysis of the major channel protein genes (such as SCN5A, RYR2, KCHN2, and KCNQ1) should be performed in these cases, in addition to histological and toxicological analyses. Only a thorough and multidisciplinary evaluation can help to better define the cases of sudden death, avoid improper classifications and clarify the pathological mechanism more precisely.