Format

Send to

Choose Destination

Links from MedGen

See comment in PubMed Commons below

Long QT Syndrome.

Source

GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
2003 Feb 20 [updated 2015 Jun 18].

Author information

1
Department of Clinical Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Excerpt

CLINICAL CHARACTERISTICS:

Long QT syndrome (LQTS) is a cardiac electrophysiologic disorder, characterized by QT prolongation and T-wave abnormalities on the ECG and the ventricular tachycardia torsade de pointes (TdP). TdP is usually self-terminating, thus causing a syncopal event, the most common symptom in individuals with LQTS. Syncope typically occurs during exercise and high emotions, less frequently at rest or during sleep, and usually without warning. In some instances, TdP degenerates to ventricular fibrillation and causes aborted cardiac arrest (if the individual is defibrillated) or sudden death. Approximately 50% of individuals with a pathogenic variant in one of the genes associated with LQTS have symptoms, usually one to a few syncopal spells. While cardiac events may occur from infancy through middle age, they are most common from the pre-teen years through the 20s. Some types of LQTS are associated with a phenotype extending beyond cardiac arrhythmia. In addition to the prolonged QT interval, associations include muscle weakness and facial dysmorphism in Andersen-Tawil syndrome (LQTS type 7), hand/foot, facial, and neurodevelopmental features in Timothy syndrome (LQTS type 8) and profound sensorineural hearing loss in Jervell and Lange-Nielson syndrome.

DIAGNOSIS/TESTING:

Diagnosis of LQTS is established by prolongation of the QTc interval in the absence of specific conditions known to lengthen it (for example, QT-prolonging drugs) and/or by molecular genetic testing that identifies a diagnostic change (or changes) in one or more of the 15 genes known to be associated with LQTS, of which KCNQ1 (locus name LQT1), KCNH2 (LQT2) and SCN5A (LQT3) are the most common. Other, less frequently involved genes are ANK2 (LQT4), KCNE1 (LQT5), KCNE2 (LQT6), KCNJ2 (LQT7), CACNA1C (LQT8), CAV3 (LQT9), SCN4B (LQT10), AKAP9 (LQT11), SNTA1 (LQT12), KCNJ5 (LQT13), CALM1 (LQT14), and CALM2 (LQT15). Approximately 20% of families meeting clinical diagnostic criteria for LQTS do not have detectable pathogenic variants in one of the above genes. LQTS associated with biallelic pathogenic variants or heterozygosity for pathogenic variants in two different genes (i.e., digenic pathogenic variants) is generally associated with a more severe phenotype with longer QTc interval and a higher incidence of cardiac events.

MANAGEMENT:

Treatment of manifestations: Beta-blocker medication is the primary treatment for LQTS; possible implantable cardioverter-defibrillators (ICD) and/or left cardiac sympathetic denervation (LCSD) for those with beta-blocker-resistant symptoms, inability to take beta blockers, and/or history of cardiac arrest. Sodium channel blockers can be useful as additional pharmacologic therapy for patients with a QTc interval >500 ms. Prevention of primary manifestations: Beta blockers are clinically indicated in all asymptomatic individuals meeting diagnostic criteria, including those who have a pathogenic variant on molecular testing and a normal QTc interval. In general, ICD implantation is not indicated for individuals with LQTS who are asymptomatic and who have not been tried on beta blocker therapy. Prophylactic ICD therapy can be considered for individuals with LQTS who are asymptomatic but suspected to be at very high risk (e.g., those with ≥2 pathogenic variants on molecular testing). Surveillance: Regular assessment of beta-blocker dose for efficacy and adverse effects in all individuals with LQTS, especially children during rapid growth; regular periodic evaluations of ICDs for inappropriate shocks and pocket or lead complications. Agents/circumstances to avoid: Drugs that cause further prolongation of the QT interval or provoke torsade de pointes; competitive sports/activities associated with intense physical activity and/or emotional stress for most individuals. Evaluation of relatives at risk: Presymptomatic diagnosis and treatment is warranted in relatives at risk to prevent syncope and sudden death. Other: For some individuals, availability of automatic external defibrillators at home, at school, and in play areas.

GENETIC COUNSELING:

LQTS is typically inherited in an autosomal dominant manner. An exception is LQTS associated with sensorineural deafness (known as Jervell and Lange-Nielsen syndrome), which is inherited in an autosomal recessive manner. Most individuals diagnosed with LQTS have an affected parent. The proportion of LQTS caused by a de novo pathogenic variant is small. Each child of an individual with autosomal dominant LQTS has a 50% risk of inheriting the pathogenic variant. Penetrance of the disorder may vary. Prenatal testing for pregnancies at increased risk and preimplantation genetic diagnosis are possible once the pathogenic variant(s) have been identified in the family.

Copyright © 1993-2017, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Support Center