The interpretation of genetic tests in inherited cardiovascular diseases

Abstract

The inherited cardiovascular diseases, including cardiomyopathies, channelopaties and inherited diseases of the aorta are heterogeneous conditions with highly variable morphologic and functional features, clinical presentation, evolution and prognosis. Hundreds of mutations in different genes have been associated with each one of these entities and it is likely that this genetic heterogeneity is one of the main reasons for the variability in their clinical expression. Information from the genetic studies may help the clinicians to diagnose the diseases in early stages, to identify relatives at risk and those who do not require periodic follow up, and may also provide prognostic information. An appropriate and accurate interpretation of the genetic tests is required to get all the potential advantages of these studies. This interpretation is not simple and requires information, specialized knowledge and dedication to the task. The first step is to decide which the appropriate genetic test is. Negative results do not exclude the disease and in that situation we need to decide whether to continue the screening or not. When the genetic study identifies one or multiple genetic variants we will have to evaluate their frequency in the general population (polymorphisms vs. mutations) and their pathogenicity. To establish whether a given variant is associated with the disease we have to integrate both basic and clinical information. When a variant is considered potentially pathogenic we still have to evaluate whether this variant explains the phenotype of the patient and of his/her family (more than one mutation may be present). Finally, we have to analyse all the available information about the consequences of the identified mutations and to integrate this information with all the available clinical data of the patient and family. With this approach, genetic test becomes a very useful tool in the management of all the inherited cardiovascular diseases.

Keywords

• genetics, cardiomyopathies, channelopaties, cardiovascular diseases.