[Meaningful diagnostics: genetics]

Abstract

Molecular genetic analysis is an important component in the diagnostics of some cardiovascular diseases; however, genetic testing should not be used as a screening technique as the diagnostic value strongly depends on anamnestic and clinical factors, such as a positive family history and the disease phenotype. In cardiovascular diseases with high mutation detection rates, e.g. hypertrophic cardiomyopathy and primary arrhythmia syndromes (long QT syndrome, catecholaminergic polymorphic ventricular tachycardia) genetic testing should be included in the diagnostic work-up. Family screening of first-degree relatives (cascade screening) is a particularly important application of genetic diagnostics for a timely identification of asymptomatic mutation carriers and initiation of preventive treatment. A molecular autopsy, also known as postmortem molecular genetic DNA testing, is a special indication for genetic diagnostics. It is particularly useful in the analysis of sudden cardiac death victims for the identification of disease-specific gene mutations. Therefore, given a selective use and a thorough evaluation of the test results, molecular genetic analyses can make a meaningful diagnostic and prognostic contribution. Potential applications of genetic analyses in the future are polygenic cardiovascular diseases. The use of new high-throughput technologies enables the analysis of multiple genetic variants, which can then be included in the calculation of a polygenic risk score for the prediction of the probability of a specific disease.

Keywords: Cardiovascular diseases; Cascade screening; Genetic testing; Molecular autopsy; Polygenic risk scores.