Genetics and Molecular Biology of the Inherited Long QT Syndrome

Abstract

Two forms of the inherited long QT syndrome have been known for many years: the autosomal recessive Jervell and Lange-Nielsen form and the autosomal dominant Romano-Ward form. A gene marker at the 11p 15.5 locus has been identified for some, but not all, families with the autosomal dominant form, but as yet the gene has not been identified. It is apparent that mutations of at least four genes, and possibly more, can cause the syndrome.

The molecular biology of the syndrome is not yet clarified, but abnormalities of ion channel function are likely, particularly the potassium delayed rectifier current. Proposals for the pathophysiology include an abnormality of a G protein which controls ion channel and adrenergic pathway function, as well as a disturbance of the sympathetic nervous system. The identification of the abnormal gene(s) and the gene products will provide precise information on the molecular physiology of the syndrome.

Key Words:

• long QT
• syncope
• sudden death
• ion channels
• after depolarizations
• gene mapping