Genetics Primer for the General Cardiologist Impact of Genetic Insights Into Mendelian Disease on Cardiovascular Clinical Practice

Recent advances in the field of genetics have significantly enhanced our understanding of many cardiovascular conditions and improved diagnosis as well as management of these disorders. However, mendelian cardiovascular diseases still pose unique challenges to clinicians, especially when presented with inherited conditions that have a wide range of phenotypic presentations. In cardiovascular single-gene disorders with potentially devastating initial manifestations, such as sudden cardiac death (SCD) or aortic dissection, appropriate and prompt identification of individuals at risk is imperative. In addition, the management of the disease is not only applicable to the individuals at risk but also extends to other members in the family. Therefore, the general approach to patients with such diseases and their affected family members needs to be considered in the context of fundamental principles of mendelian inheritance. Numerous examples of cardiovascular mendelian disorders exist in which the importance of genetics has been clearly recognized, and most common monogenic cardiovascular disorders are transmitted in families in an autosomal dominant fashion. In such autosomal dominant disorders, it is important to remember the overriding principle that any first-degree relative of an individual with an autosomal dominant multigenerational familial cardiovascular disorder has a 50% chance of also being affected by this genetic trait. Thus, when added to a family history, any symptom or sign on history, clinical evaluation, or testing that is consistent with the diagnosis in question creates a 50% likelihood that the family member is affected by the disorder as well. In this review, we will focus on a few examples of such autosomal dominant disorders to highlight the current state of clinical practice in these mendelian disorders as shaped by classic and modern genetics.