Molecular autopsy in sudden cardiac death


  • Oscar Campuzano 1. Medical Science Department, School of Medicine, Universitat de Girona, 17003 Girona, Spain 2. Cardiovascular Genetics Center, University of Girona-IDIBGI, 17190 Girona, Spain 3. Centro de Investigación Biomédica en Red, Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain
  • Georgia Sarquella-Brugada 1. Medical Science Department, School of Medicine, Universitat de Girona, 17003 Girona, Spain 4. Pediatric Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, University of Barcelona, 08950 Barcelona, Spain 5. European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), 1105 AZ Amsterdam, The Netherlands 6. Arrítmies pediàtriques, Cardiologia Genètica i Mort sobtada, Malalties Cardiovasculars en el Desenvolupament, Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, 08950 Barcelona, Spain



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.






Review articles