Inherited primary arrhythmia syndromes are genetically determined disorders of cardiac ion channels or ion channel macromolecular complexes usually associated with a higher risk of sudden cardiac death. These conditions have a very broad spectrum of clinical manifestations, ranging from an asymptomatic course to syncope, atrial and ventricular arrhythmias, and conduction disturbances, but may produce sudden infant death syndrome and unexplained sudden cardiac death in apparently healthy individuals. During the last 20 years, the evolving knowledge on the genetic basis of inherited arrhythmia syndromes has dramatically reshaped our understanding of these conditions and, consequently, had a great impact on patient care. Based on the knowledge of the genetic substrates, specific risk factors for individual genotypes have been identified, and various investigations have been launched with the intention of developing a gene- and even mutation-specific therapy. Preliminary results from animal studies suggest that gene therapy rescues the normal ion channel function and thereby prevents cardiac events in some primary arrhythmia syndromes, which suggests that upon appropriate validation in a clinical setting, it may become available for affected patients. The purpose of this review is to provide clinicians with a contemporary insight into the role of genetic testing in the diagnosis, therapy, and prognosis of patients with primary arrhythmia syndromes, and the clinical implications of screening family members who are at risk of sudden cardiac death.
From the Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Disclosure: The authors have no conflicts of interest to report.
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Correspondence: Argelia Medeiros-Domingo, MD, PhD, Arrhythmias and Cardiogenetics, Department of Cardiology, Inselspital, Bern University Hospital, Freiburgstrasse 10, 3010 Bern, Switzerland. E-mail: firstname.lastname@example.org.