LQTS

Long QT syndrome (LQTS) is a cardiac channelopathy characterized by a prolongation of the QT interval on surface electrocardiography. This electrical abnormality predisposes affected individuals to torsades de pointes, a specific polymorphic ventricular tachycardia, and to sudden cardiac death, particularly under stress or during sleep.

Most cases are congenital, inherited in autosomal dominant fashion as Romano-Ward syndrome, or in autosomal recessive form with deafness known as Jervell and Lange-Nielsen syndrome. The majority of congenital LQTS results from mutations in ion-channel genes, most notably KCNQ1 (LQT1), KCNH2 (LQT2), and SCN5A (LQT3). Other genes such as KCNE1 and KCNE2 contribute in smaller fractions.

Pathophysiology involves loss or dysfunction of cardiac potassium or sodium channels, delaying repolarization and prolonging the QT interval. This creates a substrate for early afterdepolarizations and torsades de pointes. Symptoms and risk profiles vary by genotype: LQT1 events are often triggered by exercise, LQT2 by startling or emotional stimuli, while LQT3 events frequently occur at rest or during sleep.

Diagnosis relies on a prolonged corrected QT interval (QTc) on ECG, typically exceeding around 480 ms in adults. Clinical assessment uses family history and, when available, Schwartz score. Genetic testing can confirm the diagnosis and guide family screening. It is essential to distinguish congenital LQTS from acquired QT prolongation due to medications or electrolyte disturbances.

Management aims to reduce arrhythmic risk. Avoidance of QT-prolonging drugs and correction of electrolyte abnormalities is foundational. Beta-blocker therapy, especially nadolol or propranolol, is first-line. High-risk individuals may require left cardiac sympathetic denervation or an implantable cardioverter-defibrillator.

Prognosis improves with treatment and risk-stratification. Congenital LQTS affects about 1 in 2,000 to 3,000 people, with substantial variation by genotype and adherence to therapy.