Postmortem Genetic Testing (Molecular Autopsy) for Sudden Unexplained Death (SUD), Unexplained Drowning, and Sudden Infant Death Syndrome (SIDS)
Molecular Autopsy in Sudden Unexplained Death and Unexplained Drowning
Giving the lethal and unsuspecting nature, LQTS and CPVT represent ideal arrhythmogenic assassins able to escape suspicion, detection, and apprehension by either a standard medico-legal autopsy or a careful evaluation of those surviving first- and second-degree relatives left behind.(16)
Recently, we have completed the largest molecular autopsy series of SUD to date.(15) Comprehensive mutational analysis of all 60 translated exons in the LQTS-associated genes: KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2, along with targeted analysis of the CPVT1- associated, RyR2-encoded cardiac ryanodine receptor was conducted in a series of 49 medical examiner referred cases of SUD. Herein, over 30% of SUD cases hosted a presumably pathogenic cardiac channel mutation with mutations in RyR2 alone accounting for nearly 15% of the cases (Figure 6).(15) In this series, sudden death was the sentinel event in all but four mutation positive SUD cases. In this study we provided molecular evidence for an underlying cardiac channelopathy as the likely cause and a fatal ventricular arrhythmia as the presumed manner of death in nearly one third of our SUD cases. Postmortem cardiac channel genetic testing should be considered as a standard part of the evaluation of autopsy negative, sudden unexplained death.
Molecular Autopsy in Sudden Infant Death Syndrome
In addition, unveiling such cardiac channel mutations has not been confined to only molecular autopsy investigations of SUD in children, adolescents and adults, but has also been extended to sudden infant death syndrome (SIDS). To date, postmortem genetic testing for cardiac channel mutations has been completed for a large population-based cohort of SIDS cases revealing mutations in 5 to 10% of cases (Figure 7).(17,18)