Authors' objectives:

Review evidence to determine if genetic testing for LQTS improves health outcomes for patients with known or suspected LQTS.

Authors' recommendations: There is no direct evidence that use of genetic testing for LQTS improves outcomes. Although there are limitations in the evidence on analytic validity, clinical validity, and clinical utility, nonetheless, the overall case that genetic testing will improve outcomes in selected patient populations is compelling. Conventionally, diagnosis of LQTS is based on clinical criteria. There is no gold standard for diagnosis; however, the Schwartz score has been commonly used. Two large (n>500) studies compared diagnostic performance of clinical criteria against genetic testing and genetic testing against clinical criteria, respectively. Both show that genetic testing will identify more individuals with a LQTS mutation compared to the number of patients diagnosed with LQTS by clinical methods. These findings are consistent with what is well known clinically: that there is substantial risk of underdiagnosing LQTS, with results that may be catastrophic. Despite uncertainties in the diagnostic accuracy of genetic testing, the clinical utility of testing is high. This is due to the catastrophic outcomes associated with LQTS and the availability of low-risk treatments that are efficacious in reducing adverse outcomes. The risk of undertreatment of such individuals is therefore likely to far outweigh the risk of overtreatment of such individuals. For individuals with a known LQTS mutation in the family but who do not themselves meet the clinical criteria for LQTS, genetic testing will improve outcomes. These individuals have a high pretest probability of disease and LQTS can be diagnosed with certainty if the test is positive. Treatment of these individuals with beta blockers will reduce the incidence of subsequent cardiovascular events. Furthermore, because the specific mutation is known prior to testing, the disease can be ruled out with certainty if results are negative. For other patient populations, there may be a benefit as well. For patients who have some signs and symptoms of LQTS, but no known mutation in the family, testing may be beneficial. In this situation, LQTS can be diagnosed with reasonable certainty if a class I mutation is identified, however the likelihood of false-positive results is higher than if a known mutation was present in the family. In patients with lower pretest probabilities of disease, the utility of testing declines, although precise risk/benefit thresholds cannot be established. The table provides an overview of the potential benefit of genetic testing in the spectrum of clinical populations that are encountered in practice.

Project Status: Completed

URL for project: http://www.bcbs.com/blueresources/tec/contact-tec.html

Year Published: 2007

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: BlueCross BlueShield Association

Contact Address: BlueCross BlueShield Association, Technology Evaluation Center, 225 North Michigan Ave, Chicago, Illinois, USA. Tel: 888 832 4321

Contact Name: tec@bcbsa.com

Contact Email: tec@bcbsa.com

Copyright: BlueCross BlueShield Association (BCBS)