Molecular Autopsy of Unexplained Sudden Death

Volume 5, Issue 1, June 2010

POON, WM

Senior Medical & Health Officer, Forensic Pathology Service, Department of Health

Introduction

Investigation of sudden death is the commonest challenge encountered by Forensic Pathologists. Most cases of sudden death are due to cardiovascular abnormalities evident at macroscopic and/or microscopic examination, such as coronary heart disease, myocarditis, cardiomyopathies, aortic dissection, etc. Unfortunately, a significant number of sudden death, estimated to be 1-5% (1), remains unexplained despite a thorough autopsy including toxicology, histology and other laboratory tests. This article attempts to look into some recent advances in the understanding of these “negative autopsies”. Issues related to “negative autopsies in infancy, which in itself merits another separate article, will not be covered in this article.”

Most of these cases of “negative autopsies” are believed to be caused by cardiac arrhythmias in “morphologically normal hearts” (2). Many of these “morphologically normal hearts”, however, are genetically abnormal with gene defects in ionchannels (i.e. channelopathies) in the myocytes leading to rhythm disturbances, ECG abnormalities and increased risk of sudden death. There is a growing list of inherited and congenital arrhythmia disorders caused by mutations in genes encoding defective ionic channels proteins governing the cell membrane transit of sodium, potassium and calcium ions including long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia (CPVT). 

Download Volume 5, Issue 1, June 2010

Single Tags: