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The role of molecular autopsy in unexplained sudden cardiac death

Tester, David J; Ackerman, Michael J

Current Opinion in Cardiology: May 2006 - Volume 21 - Issue 3 - p 166–172
doi: 10.1097/01.hco.0000221576.33501.83
Molecular genetics

Purpose of review 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.

Recent findings 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.

Summary 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.

Departments of Medicine, Pediatrics and Molecular Pharmacology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA

Conflicts of interest: Dr Ackerman is a consultant for Genaissance Pharmaceuticals with respect to the FAMILION™ genetic test for cardiac ion channel mutations.

Correspondence to Michael J. Ackerman, MD, PhD, Long QT Syndrome Clinic and Sudden Death Genomics Laboratory, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA Tel: +1 507 284 0101; fax: +1 507 284 3757; e-mail:

© 2006 Lippincott Williams & Wilkins, Inc.