Genetic Testing for Hypertrophic Cardiomyopathy: Ongoing Voyage from Exploration to Clinical Exploitation

Abstract

More than two decades have elapsed since the discovery that sarcomere gene defects cause familial hypertrophic cardiomyopathy (HCM). Since then, genetic testing in HCM has developed and expanded, and is now widely available as a potential clinical service in the Western countries. In the meantime, however, the cross-talk between geneticists and clinicians has developed slowly, and still remains unstandardized, with modalities of interaction and degree of mutual comprehension that vary wildly in various settings. In addition, clinicians often question the clinical utility of genetic testing in HCM patients and their families. The apparent lack of practical benefit, in the face of considerable costs, has long hindered large-scale diffusion of genetic testing, particularly in developing countries, and still accounts for understandable (but not always justifiable) resistance on the part of the physicians. However, such resistance is in contrast with considerable evidence supporting a role for molecular diagnosis in tailoring management for HCM patients. We here review several sound clinical reasons in favour of systematic genetic testing in HCM, ranging from identification of complex genotypes, heralding severe disease expression and outcome, to the added benefit of multidisciplinary genetic teamwork, enhancing awareness towards inheritable diseases in the cardiology community. We hope to show that to underestimate the clinical potential of genetic testing in HCM, and to defer its implementation until more advanced knowledge becomes available, is to lose an important opportunity for present improvement in care.

Sudden Cardiac Death in Young Athletes: Literature Review of Molecular Basis

“…54 Thus, 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 Furthermore, 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) guidelines [58][59][60][61] recommend molecular testing to improve the diagnosis and management of patients and at-risk family members.…”

Molecular genetics made simple

“…Similarly, in cases where new mutations are identified, targeted genetic tests can be designed, if needed, for screening family members at risk. Currently, different modes of cardiologist-geneticist interactions are being adopted in clinical settings around the world, a process that requires time, continuing education and to some extent, reorganization of health systems [64] . An example of such an evolving system of interdisciplinary interactions is that of the Egyptian National Genetic study of HCM ( Fig.…”