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Genotype and severity of long QT syndrome.

OBJECTIVES
To describe the state of the art of our understanding of the long QT syndromes and to provide the genetic correlation of clinical severity of patients with this disorder.


DATE SOURCES
In this review, we outline data that were obtained from work in our laboratory, as well as information reported in the literature.


STUDY SELECTION
The information in this review spans the last decade; data were obtained from the studies that had the most impact, as well as from recent work at our laboratory.


DATA EXTRACTION
The data reported herein were extracted from the world literature on sudden death and the clinical aspects of long QT syndrome. The genes identified to date, mutations in these genes, and the biophysical perturbations in the mutated ion channels, as well as the severity of disease, are detailed.


DATA SYNTHESIS
The extracted data are described as a state-of-the-art review.


CONCLUSIONS
The long QT syndromes, genetically heterogeneous disorders due to mutations in genes encoding ion channels, are relatively common causes of syncope and sudden death. The affected genes, along with the genetic background of individuals, determine the clinical severity of disease. An understanding of the mechanisms responsible for long QT syndrome is expected to enable development of specific therapies.