Purpose of review: As genetic testing for long QT syndrome (LQTS) has become readily available, important advances are being made in understanding the exact link between ion channel mutation and observed phenotype. This paper reviews recent findings in the literature.
Recent findings: Congenital LQTS is an important cause of sudden cardiac death. To date, 12 genes have been identified as the cause of congenital LQTS. With increasing availability of genetic testing, subtype-specific management of LQTS has become the standard of care. Detailed correlative studies between LQTS mutations and clinical phenotypes are leading the field towards 'mutation-specific' management within LQTS subtypes. A clear link between the distinct functional/biophysical defect in each LQT mutation and disease phenotype is complicated by the variable penetrance and pleiotropic expression of clinical phenotype. This is especially evident with the overlap syndrome now documented for several sodium channel (SCN5A) mutations.
Summary: The management of LQTS has become subtype-specific due to the availability of genotype information. Review of recent literature suggests that 'mutation-specific' management is possible based upon distinct functional/biophysical characteristics of mutations within each LQT gene. Further research is required to clearly delineate the molecular and cellular mechanisms underlying variable penetrance, and pleiotropic expression of LQTS mutations.