About this condition
Long QT Syndrome
Long QT Syndrome (LQTS) is a cardiac channelopathy characterized by delayed ventricular repolarization — visible on ECG as a prolonged QTc interval (>470ms in males, >480ms in females). This electrical abnormality creates a substrate for torsades de pointes, a life-threatening arrhythmia that can cause syncope and sudden cardiac death. LQTS affects approximately 1 in 2,000 to 2,500 people and accounts for an estimated 3–10% of sudden cardiac death in children and young adults. There are at least 17 genetic subtypes, but three account for approximately 75% of cases: LQT1 (KCNQ1, ~35%), LQT2 (KCNH2, ~30%), and LQT3 (SCN5A, ~10%). Inheritance is predominantly autosomal dominant; the rare autosomal recessive form (Jervell and Lange-Nielsen syndrome) combines LQTS with congenital sensorineural deafness.
The three major genes encode cardiac ion channels with distinct functions. KCNQ1 and KCNH2 encode potassium channels (IKs and IKr) that repolarize the ventricle; pathogenic variants reduce potassium current, delaying repolarization. SCN5A encodes the cardiac sodium channel; mutations in LQTS cause gain-of-function variants that permit persistent inward sodium current during repolarization, also prolonging the QT interval. The genotype-phenotype correlation is clinically important: LQT1 and LQT2 arrhythmias are typically triggered by physical exertion or emotional stress; LQT3 arrhythmias often occur at rest or during sleep. Approximately 25% of clinically diagnosed LQTS patients receive no molecular diagnosis from standard genetic testing.
Identifying a pathogenic LQTS variant transforms management from symptomatic treatment to family-based prevention. Genetic confirmation enables cascade testing of relatives, identifying asymptomatic mutation carriers who may have normal resting ECGs (up to 36% of KCNQ1 carriers show normal QTc). Beta-blockers are first-line therapy and have been shown to reduce sudden death risk by approximately 60%; implantable cardioverter-defibrillators (ICDs) are indicated for those who remain symptomatic despite medications. Gene-specific triggers inform lifestyle counseling: LQT1 carriers avoid strenuous exercise; LQT2 carriers avoid acoustic triggers; LQT3 carriers receive bedtime monitoring. Genetic information also enables reproductive counseling and prenatal testing options.
LQT1, LQT2, and LQT3 have distinct mechanistic bases (potassium channel loss vs. sodium channel gain), genotype-specific triggers (exercise/stress vs. sleep/rest), and different responses to beta-blockade — genotyping fundamentally alters management strategy.
- Gene locus
- KCNQ1 (11p15.5-p15.4), KCNH2 (7q36.1), SCN5A (3p22.2)
