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Heterogeneity in the Inherited Long QT Syndrome

Inherited Long QT Syndrome. Heterogeneity is present in the inherited long QT syndrome and affects the diagnosis of patients. The evidence of genetic heterogeneity is clear, with at least five genetic loci responsible for the syndrome. Phenotypic heterogeneity is less well defined, but differences in QT prolongation, T wave morphology, and the risk and frequency of syncope and sudden death are very likely. Of particular importance, it is likely that there are differences in the molecular pathophysiology of the syndrome, which are dependent on the genetic substrate present. Elucidation of the specific molecular physiology of each of the genetic subtypes of long QT syndrome will not only allow precise diagnosis and, potentially, treatment of patients with the syndrome, but will enhance our understanding of the pathophysiology of arrhythmias in general, which will extend the benefit of more precise therapy to many patients in addition to those with the long QT syndrome.