Abstract
Intense athletic training and competition can rarely result in sudden cardiac death (SCD). Despite the introduction of pre-participation cardiovascular screening, especially among young competitive athletes, sport-related SCD remains a debated issue among medical personnel, sports communities and laypersons alike, and generates significant media attention. The most frequent cause of SCD is a hidden inherited cardiomyopathy, the athletes may not even be aware of. Predictive medicine, by searching the presence of pathogenic alterations in cardiac genes, may be an integrative tool, besides the conventional ones used in cardiology (mainly electro and echocardiogram), to reach a definitive diagnosis in athletes showing signs/symptoms, even borderline, of inherited cardiomyopathy/ channelopathy, and in athletes presenting family history of SCD and/or of hereditary cardiac disease. In this review, we revised the molecular basis of the major cardiac diseases associated to sudden cardiac death and the clinical molecular biology approach that can be used to perform risk assessment at DNA level of sudden cardiac death, contributing to the early implementation of adequate therapy. Alterations can occur in ion channel genes, in genes encoding desmosomal and junctional proteins, sarcomeric and Z-disc proteins, proteins for the cytoskeleton and the nuclear envelope. The advent of next generation sequencing (NGS) technology has provided the means to search for mutations in all these genes, at the same time. Therefore, this molecular approach should be the preferred methodology for the aforementioned purpose.
Highlights
sudden cardiac death (SCD) in athletes and to discover optimal young subjects
The most common which occurs when mutations within the Cardiac channelopathies are rare inhercauses of sport-related SCD in adolescents same gene can produce different pheno- ited primary electrical disorders, without and young adults are inherited cardiomy- types, and genetic heterogeneity, occur- evidence of structural cardiomyopathy, opathies,[18,23,24,25,26,27,28,29,30,31] a clinically heterogeneous ring when mutations within different resulting from dysfunction of cardiac ion group of heart muscle disorders, character- genes produce the same phenotype
Athletes, asympalterations can affect ion channel anchoring through the identification of further variants tomatic, may be at risk of SCD while and trafficking, causing an imbalance in car- associated with the disease phenotype, they’re training or competing, due to cardiac ionic homeostasis with subsequent allows to obtain information on possi- diovascular defects they may not even be action potential and conduction alterations ble additional genetic factors that can act as aware of
Summary
The clinical molecular biol- molecular autopsy[22] in addition to the stantool for improving health and helps to pre- ogy laboratory has acquired an increasingly dard autopsy, as it may allow the post-. Electrocardiography, echocardiography and cardiac magnetic resonance imaging may not reveal subclinic anomalies present in asymptomatic subjects harbouring mutations.[54] genetic test in the proband and cascade family screening is a valuable tool to exactly diagnose an inherited cardiomyopathy and to identify family members at disease-risk in preclinical stage.[55] bioinformatics approach and functional studies can help to predict the pathogenicity of new variants found during genetic screening.[56,57] In this regard, ESC and American Heart Association (AHA)/American College of Cardiology (ACC) guidelines5861 recommend molecular testing to improve the diagnosis and management of patients and at-risk family members. Mutations in these genes may cause loss or gain of channel function, mixed effects on ion new cardiomyopathy classification system channels are reported.[65,66,67]
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