The role of molecular autopsy in unexplained sudden cardiac death.
OBJECTIVE
Sudden cardiac death (SCD) is one of the most common causes of death, with many attributable to cardiac/coronary abnormalities evident at autopsy. A significant number of SCDs, however, particularly in young people, remain unexplained following a medico-legal investigation, including autopsy, and are referred to as autopsy-negative sudden unexplained death (SUD). Due to molecular advances, however, a cardiac channel molecular autopsy may potentially provide a pathogenic basis for SUD and establish cause and manner of death.


RESULTS
Over the past decade, five population-based investigations of sudden death in young people elucidated the frequency of and causes responsible for these tragic events. The most inclusive epidemiologic study concluded that nearly 30% of SCDs in young people are autopsy-negative (i.e. SUD) and most likely secondary to cardiac channelopathies. Case reports on the post-mortem molecular diagnosis of cardiac channelopathies through the use of a molecular autopsy have been presented. Recently, a molecular autopsy series of SUD identified pathogenic mutations in long QT syndrome and catecholaminergic polymorphic ventricular tachycardia-associated genes in over one-third of cases. Similar post-mortem cardiac channel genetic testing in a large population-based cohort of sudden infant death syndrome has elucidated mutations in 5-10% of cases.


CONCLUSIONS
With autopsy-negative SUD accounting for a significant number of sudden deaths in young people, a new role for the medical examiner is emerging. An accurate diagnosis, derived from a molecular autopsy, will guide the appropriate initiation of pre-emptive strategies in hopes of preventing future tragedies among those left behind.
Tester
David J
DJ
Departments of Medicine, Pediatrics and Molecular Pharmacology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Ackerman
Michael J
MJ
D000293:Adolescent; D000328:Adult; D001145:Arrhythmias, Cardiac / Q000235:genetics* / Q000401:mortality; D001344:Autopsy; D002423:Cause of Death / Q000639:trends; D002648:Child; D002675:Child, Preschool; D016757:Death, Sudden, Cardiac / Q000209:etiology* / Q000473:pathology; D049429:Forensic Pathology; D006329:Heart Conduction System; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009154:Mutation