Congenital Long QT Syndrome: An Update and Present Perspective in Saudi Arabia

Abstract

Primary cardiac arrhythmias are often caused by defects, predominantly in the genes responsible for generation of cardiac electrical potential, i.e., cardiac rhythm generation. Due to the variability in underlying genetic defects, type, and location of the mutations and putative modifiers, clinical phenotypes could be moderate to severe, even absent in many individuals. Clinical presentation and severity could be quite variable, syncope, or sudden cardiac death could also be the first and the only manifestation in a patient who had previously no symptoms at all. Despite usual familial occurrence of such cardiac arrhythmias, disease causal genetic defects could also be de novo in significant number of patients. Long QT syndrome (LQTS) is the most eloquently investigated primary cardiac rhythm disorder. A genetic defect can be identified in ∼70% of definitive LQTS patients, followed by Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) and Brugada syndrome (BrS), where a genetic defect is found in <40% cases. In addition to these widely investigated hereditary arrhythmia syndromes, there remain many other relatively less common arrhythmia syndromes, where researchers also have unraveled the genetic etiology, e.g., short QT syndrome (SQTS), sick sinus syndrome (SSS), cardiac conduction defect (CCD), idiopathic ventricular fibrillation (IVF), early repolarization syndrome (ERS). There exist also various other ill-defined primary cardiac rhythm disorders with strong genetic and familial predisposition. In the present review we will focus on the genetic basis of LQTS and its clinical management. We will also discuss the presently available genetic insight in this context from Saudi Arabia.

Subclinical ventricular repolarization abnormality in uncontrolled compared with controlled treated hypertension

“…Therefore, we can expect that a number of our patients are at risk of sudden cardiac death because of cardiac arrhythmias. It is important to mention here that genetic factor is the cause of the prolonged of the QTcB period in some patients, but it is unlikely to be the cause of about 25% of our patients 24, 25, 26. The cause of prolonged QTcB interval in this study is acquired due to hypertension.…”

Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes as Models for Cardiac Channelopathies

“…LQTS1 results from LOF mutations in the KCNQ1 gene that encodes the α-subunit of the channel conducting I Ks . LQTS1 patients respond well to β-blockers while some are less responsive or even resistant to this medication 83 .…”

Electrophysiological properties of iPS cell-derived cardiomyocytes from a patient with long QT syndrome type 1 harboring the novel mutation M437V of KCNQ1

“…LQTSs are classified into congenital and acquired ones [4]. Previous reports described at least 15 different forms of congenital LQTSs, 45% of which are caused by mutations in KCNQ1 ( KvLQT1 or Kv 7.1) and classified as LQTS type 1 (LQT1) [4], [5], [6], [7]. KCNQ1 encodes the alpha subunit of the channel generating slowly-activating delayed-rectifier K + currents (I Ks ) that are responsible for the repolarization of ventricular myocytes [2].…”