Long QT Syndrome

Descriptive text is not available for this imageBASICS

DESCRIPTION

  • Long QT syndrome (LQTS) is a genetic disorder of prolonged repolarization of the cardiac myocytes that predisposes patients to ventricular arrhythmias, torsade de pointes (TdP), cardiac arrest, and sudden cardiac death.
  • LQTS is diagnosed by the presence of a prolonged heart rate corrected QT interval (QTc) on a 12-lead electrocardiogram (ECG) and any of the following:
    • History of aborted sudden cardiac arrest or sudden cardiac death
    • Family history consistent with LQTS
    • Genetic testing revealing pathogenic mutation consistent with LQTS
    • Concerning cardiac symptoms including exercise-induced dizziness, syncope, or seizures
  • LQTS was first described in 1957 by Jervell and Lange-Nielsen as a syndrome that included QT prolongation, congenital deafness, and high incidence of sudden cardiac death.
  • Reports followed in the early 1960s by Romano and Ward of a similar clinical picture in the absence of congenital deafness

EPIDEMIOLOGY

  • The exact prevalence of LQTS is unknown but has been estimated to be between 1:2,000 and 1:10,000 live births.
  • LQTS is more common in females.
  • LQTS most commonly presents during childhood, adolescence, or early adulthood.
  • Congenital LQTS can present at birth with significant QTc prolongation (>500 msec), bradycardia, high-grade atrioventricular block, and hemodynamic instability.
  • The first presentation of LQTS can be cardiac arrest or sudden cardiac death.

ETIOLOGY

LQTS is a genetic disorder caused by pathogenic mutations in multiple genes involved in repolarization of the cardiac myocytes and includes abnormalities in potassium, calcium, and sodium channel genes.

RISK FACTORS

Genetics

  • Genetic testing is positive in approximately 70% of patients with LQTS, and 5–10% of mutations arise de novo.
  • There are currently 15 types of LQTS based on current genetic testing, although the 3 most common types encompass >75% of all cases of LQTS.
    • LQTS type 1 is caused by a mutation in the KCNQ1 gene (potassium channel), and cardiac events typically are associated with swimming, diving, or activity/exercise.
    • LQTS type 2 is caused by a mutation in the KCNH2 gene (potassium channel), and cardiac events typically are associated with emotional stress or sudden loud noises.
    • LQTS type 3 is caused by a gain of function mutation in SCN5A (sodium channel), and cardiac events typically are associated with rest or sleep.
  • LQTS type 3 is a common arrhythmic cause of sudden infant death syndrome (SIDS).

GENERAL PREVENTION

Patients with LQTS should avoid the use of medications known to prolong the QT interval. A list of these medications can be found via https://www.crediblemeds.org/

PATHOPHYSIOLOGY

  • LQTS is a primary electrical disorder of the heart.
  • The mechanism of tachycardia in LQTS patients is a triggered activity due to afterdepolarizations during a period of electrical relaxation.
  • Abnormal prolongation of the repolarization portion of the cardiac myocyte action potential predisposes to early and late afterdepolarizations and the potential for abnormal cardiac rhythms including ventricular tachycardia, ventricular fibrillation, and TdP.

COMMONLY ASSOCIATED CONDITIONS

  • Andersen-Tawil syndrome (formerly LQTS type 7)
    • Disorder characterized by periodic paralysis, syndactyly of the toes, clinodactyly of the 5th digit, and facial features (small mandible, low-set ears, widely spaced eyes)
    • Caused by a mutation in the KCNJ2 gene and there is an association with QTc prolongation, enlarged U waves, and ventricular arrhythmias
  • Timothy syndrome (formerly LQTS type 8)
    • Disorder characterized by syndactyly of the fingers and toes, developmental delay, hypotonia, seizures, facial features (depressed nasal bridge, low-set ears, round face) along with congenital heart disease (atrial and ventricular septal defects, tetralogy of Fallot)
    • Caused by a mutation in the CACNA1 gene and is associated with a risk of QTc prolongation and ventricular arrhythmias and an average age of death of 2.5 years

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