Genetic testing

Within the field of molecular cardiac electrophysiology, the previous two decades of research have elucidated the fundamental genetic substrates underlying many arrhythmogenic disorders associated with sudden cardiac death including long QT syndrome (LQTS), Andersen-Tawil syndrome, Timothy syndrome, short QT syndrome (SQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), Brugada Syndrome (BrS), familial AV block, early repolarization syndrome, and atrial fibrillation. In addition, the molecular underpinnings for structural cardiomyopathies vulnerable to sudden arrhythmic death: dilated cardiomyopathy, hypertrophic cardiomyopathy, left ventricular noncompaction syndrome, and arrhythmogenic right ventricular cardiomyopathy, are understood now in greater detail. Gene testing for several of these heritable channelopathies and cardiomyopathies are currently available through specialized clinical and/or research based laboratories. The purpose of this chapter is to equip the reader with a basic understanding of molecular genetics and genetic testing in the setting of cardiac electrophysiologic disorders. First, the chapter will present a primer on fundamental molecular genetics including the organization of the human genome, transfer of genetic information, different modes of inheritance, and types of mutations in human genetic disease. Next, techniques utilized in genetic testing will be illustrated. And finally, this chapter will address the important issues of genetic testing, including clinical versus research based testing, benefits of genetic testing, limitations to genetic testing, interpretation of the genetic test, role of genetic counselors, and ethical, legal and societal implications.