MOLECULAR GENETICS: Edited by Ali J MarianThe impact of genetics on the long QT syndrome: myth or reality?Schwartz, Peter J.a; Sala, Lucaa,b Author Information aIstituto Auxologico Italiano IRCCS, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics bDepartment of Biotechnology and Biosciences, University of Milano - Bicocca, Milan, Italy Correspondence to Peter J. Schwartz, MD, Center for Cardiac Arrhythmias of Genetic Origin, Istituto Auxologico Italiano IRCCS, Via Pier Lombardo, 22, 20135 Milan, Italy. Tel: +3902619113408; fax: +3902619113411; e-mail: [email protected]; [email protected] Current Opinion in Cardiology 38(3):p 149-156, May 2023. | DOI: 10.1097/HCO.0000000000001027 Buy Metrics Abstract Purpose of review To summarize and critically assess the contribution of genetics to the Long QT Syndrome (LQTS), with specific reference to the unraveling of its underlying mechanisms and to its impact on clinical practice. Recent findings The evolution towards our current approach to therapy for LQTS patients is examined in terms of risk stratification, gene-specific management, and assessment of the clinical impact that genetic modifiers may have in modulating the natural history of the patients. Glimpses are provided on the newest multidisciplinary approaches to study disease mechanisms, test new candidate drugs and identify precision treatments. Summary It is undeniable that genetics has revolutionized our mechanistic understanding of cardiac channelopathies. Its impact has been enormous but, curiously, the way LQTS patients are being treated today is largely the same that was used in the pregenetic era, even though management has been refined and gene-specific differences allow a more individually tailored antiarrhythmic protection. The synergy of genetic findings with modern in vitro and in silico tools may expand precision treatments; however, they will need to prove more effective than the current therapeutic approaches and equally safe. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.