Molecular biology and the prolonged QT syndromes

The prolonged QT syndromes are characterized by prolongation of the QT inte rval corrected for heart rate (QTc) on the surface electrocardiogram associ ated with T-wave abnormalities, relative bradycardia, and ventricular tachy arrhythmias, including polymorphic ventricular tachycardia and torsades de pointes. These patients tend to present with episodes of syncope, seizures, or sudden death typically triggered by exercise, emotion, noise, or, in so me cases, sleep. These disorders of cardiac repolarization are commonly inh erited, with the autosomal dominant form, Romano-Ward syndrome, most common . A rare autosomal recessive form associated with sensorineural deafness, J ervell and Lange-Nielsen syndrome, in which the cardiac disorder is autosom al dominant and deafness is a recessive trait, also occurs. The underlying genetic causes of these forms of prolonged QT interval syndromes are hetero geneous, with at least seven genes responsible for the clinical syndromes. All of the five genes identified to date encode ion channel proteins, sugge sting this to be an ion channelopathy. In this review, the genetic basis of the prolonged QT interval syndromes will be discussed, genotype-phenotype correlations identified, and the approaches to genetic testing and treatmen ts will be outlined. (C) 2001 by Excerpta Medica, Inc.