Cardiac genetic investigation of sudden cardiac death: advances and remaining limitations

Directing a thorough postmortem investigation of a young sudden unexpected death is one opportunity that a forensic pathologist has to save lives. Achieving a diagnosis of an inherited heart condition in the decedent means that family members can be screened for the condition and effective protective therapies can be put into place. Since these conditions are almost always autosomal dominant, 50% of family members are at risk. Diagnosis is achieved through a thorough high-quality autopsy examination, storage and analysis of DNA, and involvement of the family in the investigation, including cardiac tests upon them. Forensic pathologists should form a partnership with a cardiac genetic service and liaise with them in cases of sudden unexplained death, particularly in 1- to 40-year olds, and when cardiomyopathy is diagnosed at autopsy. The molecular autopsy in sudden unexplained death should include the most common long QT genes and RyR2, the cardiac ryanodine gene linked to catecholaminergic polymorphic ventricular tachycardia. Alternatively or in addition, genetic testing can be guided by cardiac findings in first-degree relatives. With such an approach, a diagnosis can be achieved in up to 50%. Most sudden death in young people occurs at sleep, rest or light activity, and not during sport. Pathologists should be aware that long QT and catecholaminergic polymorphic ventricular tachycardia can be misdiagnosed as epilepsy in life. These ion channelopathies and the cardiomyopathies such as hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy can present with drowning in a competent swimmer, straight road car accidents, and death that can be triggered by certain medications or toxins.