The molecular autopsy: should the evaluation continue after the funeral?

Abstract

Sudden cardiac death (SCD) is one of the most common causes of death in developed countries, with most SCDs involving the elderly, and structural heart disease evident at autopsy. Each year, however, thousands of sudden deaths involving individuals younger than 35 years of age remain unexplained after a comprehensive medicolegal investigation that includes an autopsy. In fact, several epidemiologic studies have estimated that at least 3% and up to 53% of sudden deaths involving previously healthy children, adolescents, and young adults show no morphologic abnormalities identifiable at autopsy. Cardiac channelopathies associated with structurally normal hearts such as long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and Brugada syndrome (BrS) yield no evidence to be found at autopsy, leaving coroners, medical examiners, and forensic pathologists only to speculate that a lethal arrhythmia might lie at the heart of a sudden unexplained death (SUD). In cases of autopsy-negative SUD, continued investigation through either a cardiologic and genetic evaluation of first- or second-degree relatives or a molecular autopsy may elucidate the underlying mechanism contributing to the sudden death and allow for identification of living family members with the pathogenic substrate that renders them vulnerable, with an increased risk for cardiac events including syncope, cardiac arrest, and sudden death.

Fig. 1

The prevalence of cardiac channelopathy in sudden infant death syndrome (SIDS). The pie chart shows that approximately 10% of SIDS cases result from cardiac channelopathy sudden death-related disorders including long QT syndrome (LQTS), Brugada syndrome (BrS), and catecholaminergic polymorphic ventricular tachycardia (CPVT)

Fig. 2

The prevalence of sudden unexplained death (SUD) in a retrospective autopsy series of individuals with autopsy-negative “structurally normal hearts.” It is estimated that at least 3% and perhaps as many as 53% of sudden deaths involve previously healthy children, adolescents, and young adults with no identifiable morphologic abnormalities found at autopsy (“structurally normal heart”), and the SCD is labeled as autopsy-negative SUD. The bar graph shows the percentage of autopsy-negative “structurally normal hearts” identified during 10 retrospective analyses of large population–based autopsy cohorts [13, 18, 22, 26, 28, 43, 45, 54, 73, 74]