Genetic Biomarkers in Cardiovascular Disease

Abstract

Inherited cardiac conditions (ICCs) are a group of largely monogenic disorders affecting the heart, its conducting system and its vasculature. When an ICC is diagnosed in an individual, there are implications for the wider family circle, particularly the first-degree relatives. The understanding of the molecular pathology of ICCs has dramatically improved with advances in molecular genetics, and genetic testing is increasingly available as part of the diagnostic and predictive tools available for the management of these disorders. Genetic tests offer many advantages over traditional cardiovascular tests. They do not require invasive sampling, have high accuracy and can be performed whether or not symptoms of disease are present. The indications for performing a genetic test in ICCs are broadly divided into diagnostic testing and presymptomatic testing or cascade screening. Diagnostic testing is performed in most cases on the proband, the first individual in the family with observed signs and/or symptoms of disease, with a goal of establishing a precise diagnosis. Genetic testing can achieve this without sampling the affected tissue and can serve as a basis for treatment, anticipatory guidance and genetic counseling. Presymptomatic testing or cascade screening is applied to individuals who are yet to present signs or symptoms of disease, but are identified as at risk on the basis of family history. Genetic testing can determine the risk of disease, but it cannot be guaranteed whether or not the disease will become symptomatic. ICCs are a group of highly heterogeneous disorders, both clinically and genetically, and the first indication that an individual is affected with an ICC can be when they present with a sudden cardiac death. In the UK, the National Service Framework for coronary disease sets out,