When a young athlete collapses and dies on a field, the tragedy extends far beyond one individual — because the genetic variant responsible may be silently circulating through an entire family. This review reframes sudden cardiac death in sport not merely as a forensic problem but as a heritable, preventable risk signal that demands cascade family screening.
The review, published in Molecular Diagnosis & Therapy, examines inherited arrhythmogenic syndromes — including conditions such as long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, and arrhythmogenic cardiomyopathy — as the principal molecular drivers of exercise-related sudden cardiac death in athletes. A critical and often underappreciated dimension highlighted is toxicological co-exposure: high doses of certain substances, including performance-enhancing compounds or pharmacological agents, can potentiate arrhythmic risk in genetically susceptible hearts, creating a compound vulnerability that standard pre-participation screening typically misses. The authors advocate for molecular autopsy — genetic sequencing performed postmortem — as both a diagnostic closure tool and a public health instrument that can trigger life-saving testing in surviving relatives.
This multidisciplinary framing — integrating forensic, clinical, genetic, and toxicological data — reflects a meaningful maturation in sports cardiology thinking. Historically, sudden cardiac death investigations stopped at autopsy findings or electrocardiogram anomalies; incorporating next-generation sequencing into postmortem protocols is still far from standard practice globally. The practical implication is substantial: identifying a pathogenic variant in a deceased athlete may confer a preventable diagnosis on siblings or parents who share the mutation, for whom implantable defibrillators or activity modification could be lifesaving. However, this review is a narrative synthesis rather than a large prospective cohort study, so quantitative yield estimates for molecular autopsies vary considerably across existing literature (roughly 20–35% positive identification rates). The central contribution is methodological and conceptual — positioning personalized molecular diagnosis as the connective tissue between forensic medicine and preventive cardiology.
