Molecular biological and genetic approaches to the evaluation of inherited electrophysiologic disorders.

摘要

Although previously thought of as sporadic errors in development, some arrhythmias are now established to have a hereditary basis. The genetic and molecular bases of inherited cardiac arrhythmias are being recognized with increased frequency. Environmental and somatic influences may complicate classical identification of the patterns of inheritance. In several examples of inherited heart disease with a distinct molecular and genetic foundation, multiple gene defects appear to be responsible for similar phenotypes. In addition, specific genotypes may lead to differing severity of phenotype and differential prognostic risks. There is also variability in phenotypic expression, even among identical genotypes within a family, complicating risk stratification. Improved understanding of rare familial arrhythmia disorders may increase our overall comprehension of the pathophysiology of rhythm disturbances in general. The inherited arrhythmia disorders can be classified under three broad headings -- those familial arrhythmias that originate above the ventricles, familial arrhythmias originating within the ventricles and familial disorders affecting impulse propagation and cardiac conduction. Familial occurrences of tachyarrhythmias and bradyarrhythmias have been reported for each of these types of disorders. Recent discoveries of genetic etiologies have shed new light on the mechanisms underlying arrhythmogenesis and molecular genetics of cardiac electrophysiology.