Impact of laboratory molecular diagnosis on contemporary diagnostic criteria for genetically transmitted cardiovascular diseases: hypertrophic cardiomyopathy, long-QT syndrome, and marfan syndrome : A statement for healthcare professionals from the councils on clinical cardiology, cardiovascular dis

Over the last several years, substantial progress has been achieved in defining the molecular basis for several genetically transmitted, nonatherosclerotic cardiovascular diseases. These advances in molecular biology have enhanced our understanding of the primary defects and basic mechanisms responsible for the pathogenesis of these conditions and their phenotypic expression, and in the process, new perspectives on cardiac diagnosis have been formulated. In the course of this scientific evolution, a certain measure of uncertainty has also arisen regarding the implications of genetic analysis for clinical diagnostic criteria. New subgroups of genetically affected individuals without conventional clinical diagnostic findings have been identified solely by virtue of access to molecular laboratory techniques, creating a number of medical and ethical concerns regarding the possible clinical implications. Indeed, the extent to which such individuals should receive sequential evaluations and/or therapy or be subjected to employment or insurance discrimination, psychological harm, loss of privacy, or unnecessary withdrawal from competitive athletics is uncertain but remains a legitimate source of concern. It is therefore particularly timely and appropriate to analyze these issues in detail, specifically the extent to which molecular biology has revised traditional diagnostic criteria. The role of genetic testing in assessing prognosis and identifying high-risk subgroups or in defining basic disease mechanisms and pathophysiology is, however, largely beyond the scope of this scientific statement. As models for the present critique, we selected the 3 most common familial cardiovascular diseases for which gene defects have been identified, each of which is associated with autosomal dominant inheritance and a risk for sudden cardiac death: hypertrophic cardiomyopathy (HCM), long-QT syndrome (LQTS), and Marfan syndrome (MFS).