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Genetics of congenital and acquired long QT syndrome

INTRODUCTION

The long QT syndrome (LQTS) is the phenotypic description of a group of disorders characterized by a prolonged QT interval in association with a characteristic arrhythmia, polymorphic ventricular tachycardia. The LQTS can be inherited or acquired as an adverse response to medication, metabolic abnormalities, or bradyarrhythmias. Torsades de pointes (TdP) or "twisting of points" is the specific type of polymorphic ventricular tachycardia (VT) associated with either form of the LQTS. (See "Clinical features of congenital long QT syndrome" and "Acquired long QT syndrome".)

Modern molecular biological techniques have permitted the identification and analysis of the genes responsible for almost all patients with a congenital long QT syndrome (table 1 and figure 1) [1-7]. Hundreds of mutations in more than ten genes have thus far been identified [8]. Distinct genetic types have been designated LQT1 through LQT10 and additional genetic types have been identified.

Long QT syndrome can also be an acquired disorder, most often due to drugs (table 2). In some patients, drug-associated LQTS appears to represent a "forme fruste" of congenital LQTS in which a mutation or polymorphism in one of the LQTS genes is clinically inapparent until the patient is exposed to a particular drug or other predisposing factor. (See 'Mutations in acquired LQTS' below.)

The genetics of congenital and acquired LQTS will be reviewed here. The clinical features and criteria used to make the diagnosis of congenital long QT syndrome and the characteristics of acquired LQTS are discussed elsewhere. (See "Clinical features of congenital long QT syndrome" and "Diagnosis of congenital long QT syndrome" and "Acquired long QT syndrome".)

Phenotypes of congenital LQTS — Two clinical phenotypes have been described in congenital LQTS that vary with the type of inheritance and the presence or absence of sensorineural hearing loss: the Romano-Ward syndrome and the less common Jervell and Lange-Nielsen syndrome.
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