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Updated: May 18, 2026

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
Inherited long QT syndrome: clinical manifestation, genetic diagnostics, and therapy
Sven Zumhagen1, Birgit Stallmeyer, Corinna Friedrich
1Institute for Genetics of Heart Diseases (IfGH), Department of Cardiovascular Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, Gebäude D3, 48149, Münster, Germany. Sven.Zumhagen@ukmuenster.de
Abstract:
Inherited long QT syndrome (LQTS) is characterized by a prolonged ventricular repolarization (QTc interval) and symptoms (syncope, sudden cardiac arrest) due to polymorphic ventricular arrhythmias. As of today, 13 different cardiac ion channel genes have been associated with congenital LQTS. The most common ones are due to KCNQ1 (LQT-1), KCNH2 (LQT-2), and SCN5A (LQT-3) gene mutations and account for up to 75 % of cases. Typical clinical findings are an increased QT interval on the surface electrocardiogram, specifically altered T wave morphologies, polymorphic ventricular arrhythmias, or an indicative family history. Recently, in the HRS/EHRA expert consensus statement, comprehensive genetic testing of major LQTS genes was recommended for index patients for whom there is a strong clinical suspicion of LQTS. Overall, antiadrenergic therapy, in particular β-receptor blockers, has been the mainstay of therapy and has significantly reduced cardiac events. For high-risk patients, an implantable cardioverter defibrillator (ICD) is recommended. Importantly, lifestyle modification and avoidance of arrhythmia triggers are additional important approaches.
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