LQTS can arise from variants in several genes, leading in some cases to quite different features. The common thread linking these variants is that they affect one or more ion currents leading to prolongation of the ventricular action potential, thus lengthening the QT interval. Classification systems have been proposed to distinguish between subtypes of the condition based on the clinical features (and named after those who first described the condition) and subdivided by the underlying genetic variant. The commonest of these, accounting for 99% of cases, is Romano–Ward syndrome (genetically LQT1-6 and LQT9-16), an autosomal dominant form in which the electrical activity of the heart is affected without involving other organs. A less commonly seen form is Jervell and Lange-Nielsen syndrome, an autosomal recessive form of LQTS combining a prolonged QT interval with congenital deafness. Other rare forms include Anderson–Tawil syndrome (LQT7) with features including a prolonged QT interval, periodic paralysis, and abnormalities of the face and skeleton; and Timothy syndrome (LQT8) in which a prolonged QT interval is associated with abnormalities in the structure of the heart and autism spectrum disorder. Romano–Ward syndrome
LQT1 is the most common subtype of Romano–Ward syndrome, responsible for 30 to 35% of all cases. The gene responsible, KCNQ1, has been isolated to chromosome 11p15.5 and encodes the alpha subunit of the KvLQT1 potassium channel. This subunit interacts with other proteins (in particular, the minK beta subunit) to create the channel, which carries the delayed potassium rectifier current IKs responsible for the repolarisation phase of the cardiac action potential.
In most cases, modern therapy favors ICD implantation if beta blocker therapy fails. In patients considered at high risk of life-threatening arrhythmic events, ICD implantation may be considered as a preventive step. Arrhythmia termination
Arrhythmia termination involves stopping a life-threatening arrhythmia once it has already occurred. One effective form of arrhythmia termination in individuals with LQTS is placement of an implantable cardioverter-defibrillator (ICD). Also, external defibrillation can be used to restore sinus rhythm. ICDs are commonly used in patients with fainting episodes despite beta blocker therapy, and in patients having experienced a cardiac arrest. As mentioned earlier, ICDs may be used also in patients considered at high risk of life-threatening arrhythmic events.With better knowledge of the genetics underlying LQTS, more precise treatments hopefully will become available. Outcomes
Genotype and QT interval duration are the strongest predictors of outcome for patients with LQTS. These have been combined to create an externally validated risk score calculator, estimating a 5-year risk for each individual patient, which can help physicians to identify patients at the highest risk of life-threatening arrhythmic events.For people who experience cardiac arrest or fainting caused by LQTS and who are untreated, the risk of death within 15 years is around 50%. With careful treatment this decreases to less than 1% over 20 years. Those who exhibit symptoms before the age of 18 are more likely to experience a cardiac arrest. Epidemiology
Inherited LQTS is estimated to affect between one in 2,500 and 7,000 people.