Long QT Syndrome
ABSTRACT The hereditary Long QT syndrome (LQTS) is a genetic channelopathy with variable penetrance that is associated with increased propensity for polymorphic ventricular tachyarrhythmias and sudden cardiac death in young individuals with normal cardiac morphology. The diagnosis of this genetic disorder relies on a constellation of electrocardiographic, clinical, and genetic factors. Accumulating data from recent studies indicate that the clinical course of affected LQTS patients is time-dependent and age-specific, demonstrating important gender differences among age groups. Risk assessment should consider age-gender interactions, prior syncopal history, QT-interval duration, and genetic factors. Beta-blockers constitute the mainstay therapy for LQTS, while left cardiac sympathetic denervation and implantation of a cardioverter defibrillator should be considered in patients who remain symptomatic despite beta-blocker therapy. Current and ongoing studies are also evaluating genotype-specific therapies that may reduce the risk for life-threatening cardiac events in high-risk LQTS patients.
- SourceAvailable from: Hugues Abriel
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- "The most prevalent and well-known disorder in this group is congenital LQTS. The average prevalence of LQTS has been reported to be 1:2500– 1:5000 per individual (Goldenberg et al., 2008; Schwartz et al., 2009; Tester et al., 2006). Much higher LQTS prevalence numbers, 0.8–1.5% of the population, have been found in some ethnic groups with founder effects (Berge et al., 2008; Brink and Schwartz, 2009; Winbo et al., 2011). "
ABSTRACT: Channelopathies are diseases caused by dysfunctional ion channels, due to either genetic or acquired pathological factors. Inherited cardiac arrhythmic syndromes are among the most studied human disorders involving ion channels. Since seminal observations made in 1995, thousands of mutations have been found in many of the different genes that code for cardiac ion channel subunits and proteins that regulate the cardiac ion channels. The main phenotypes observed in patients carrying these mutations are congenital long QT syndrome (LQTS), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), short QT syndrome (SQTS) and variable types of conduction defects (CD). The goal of this review is to present an update of the main genetic and molecular mechanisms, as well as the associated phenotypes of cardiac channelopathies as of 2012.Gene 12/2012; 517(1). DOI:10.1016/j.gene.2012.12.061 · 2.08 Impact Factor
Frontiers in Pharmacology 04/2012; 3:72. DOI:10.3389/fphar.2012.00072 · 3.80 Impact Factor
- "). The penetrance of LQTS was reported to range between 0.25 (Priori et al., 1999) and 0.7 (Goldenberg et al., 2008), but could be higher, i.e., 0.88, for specific mutations (Brink et al., 2005). Considering an average penetrance of 0.5, the prevalence of carriage of at least 1 mutant allele should amount to about 5 × 10 −4 . "
- "The disease is relatively infrequent, with variable prevalence estimated from 1:2000 to 1:5000 (Goldenberg, et al., 2008; Schwartz, et al., 2009). QT prolongation is the hallmark of LQTS, and it may form via one of two pathways: reduction in the outward potassium current during phase 3 of the action potential ( " loss of function " ) or an augmented late entry of sodium or calcium ions into the cardiac myocytes ( " gain of function " ) (Goldenberg, et al., 2008; Moss and Kass, 2005). In 1995, Curran et al. first found LQTS caused by KCNH2 gene mutations (Curran, et al., 1995). "
Article: LQTS gene LOVD database[Show abstract] [Hide abstract]
ABSTRACT: The Long QT Syndrome (LQTS) is a group of genetically heterogeneous disorders that predisposes young individuals to ventricular arrhythmias and sudden death. LQTS is mainly caused by mutations in genes encoding subunits of cardiac ion channels (KCNQ1, KCNH2,SCN5A, KCNE1, and KCNE2). Many other genes involved in LQTS have been described recently(KCNJ2, AKAP9, ANK2, CACNA1C, SCNA4B, SNTA1, and CAV3). We created an online database(http://www.genomed.org/LOVD/introduction.html) that provides information on variants in LQTS-associated genes. As of February 2010, the database contains 1738 unique variants in 12 genes. A total of 950 variants are considered pathogenic, 265 are possible pathogenic, 131 are unknown/unclassified, and 292 have no known pathogenicity. In addition to these mutations collected from published literature, we also submitted information on gene variants, including one possible novel pathogenic mutation in the KCNH2 splice site found in ten Chinese families with documented arrhythmias. The remote user is able to search the data and is encouraged to submit new mutations into the database. The LQTS database will become a powerful tool for both researchers and clinicians.Human Mutation 11/2010; 31(11):E1801-10. DOI:10.1002/humu.21341 · 5.05 Impact Factor