Molecular autopsy in sudden cardiac death

Abstract

A post-mortem genetic analysis in the process of investigating a sudden death episode is known as ‘molecular autopsy’. It is usually performed in cases without a conclusive cause of death and after a comprehensive medico-legal autopsy. In these sudden unexplained death cases, an underlying inherited arrhythmogenic cardiac disease is the main suspected cause of death. The objective is to unravel a genetic diagnosis of the victim, but it also enables cascade genetic screening of the victim’s relatives. Early identification of a deleterious genetic alteration associated with an inherited arrhythmogenic disease may help to adopt preventive personalized measures to reduce risk of malignant arrhythmias and sudden death. It is important to remark that the first symptom of an inherited arrhythmogenic cardiac disease may the malignant arrhythmia and even sudden death. Next-generation sequencing allows a rapid and cost-effectives genetic analysis. Close interaction between the forensic scientist, pathologist, cardiologist, pediatric cardiologist and geneticist has allowed a progressive increase of genetic yield in recent years, identifying the pathogenic genetic alteration. However, large numbers of rare genetic alterations remain classified as having an ambiguous role, impeding a proper genetic interpretation and useful translation into both forensic and cardiological arena.

Molecular autopsy for sudden death in Japan

“…Molecular autopsy involves postmortem genetic analyses 16,17 . The sudden death of young individuals is associated with congenital channelopathy 17,18 .…”

“…Molecular autopsy involves postmortem genetic analyses 16,17 . The sudden death of young individuals is associated with congenital channelopathy 17,18 . Inherited arrhythmias are a cause of sudden death and include Brugada syndrome, long QT syndrome (LQTS), short QT syndrome, and catecholaminergic polymorphic ventricular tachycardia.…”

Sudden Cardiac Death in the Young: State-of-the-Art Review in Molecular Autopsy

“…Autopsy is the only tool to definitively determine the cause of death post-mortem, and according to some studies, in 5-10% of cases, the cause remains unknown, termed SUD [54,55]. Often, in these instances, the cause of SCDY is a malignant hereditary arrhythmogenic disease (MHAD) [54,55].…”

New Insights on Molecular Autopsy in Sudden Death: A Systematic Review

“…In comparison to similar studies, where the frequency with which molecular autopsy resolves cases of sudden death or the genes most commonly associated with sudden death have been investigated, the present work aimed to focus primarily on the methodological aspects of individual studies, potentially highlighting elements of incompleteness that may render these studies challenging to apply in practical and theoretical contexts [ 2 , 9 , 10 ].…”