Clinical Research
Heart Rhythm Disorder
Effect of Clinical Phenotype on Yield of Long QT Syndrome Genetic Testing

https://doi.org/10.1016/j.jacc.2005.09.056Get rights and content
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Objectives

The purpose of this study was to examine the effect of clinical phenotype on the yield of genetic testing for congenital long QT syndrome (LQTS).

Background

Since the discovery of the first LQTS susceptibility genes in 1995, numerous genotype-phenotype relationships have emerged during the past decade of research genetic testing. In May 2004, LQTS genetic testing became a clinically available molecular diagnostic test.

Methods

Blinded to genetic test results, analysis of the clinical phenotype was performed in 541 consecutive unrelated patients referred to Mayo Clinic’s Sudden Death Genomics Laboratory for LQTS genetic testing from August 1997 to July 2004.

Results

The yield of genetic testing correlated significantly with the corrected QT interval (QTc) and clinical diagnostic score ranging from 0% when QTc was <400 ms to 62% when QTc was >480 ms (p < 0.0001). Among those with the highest clinical probability, the yield was 72% (89 of 123). The yield fluctuated substantially depending on age at diagnosis in males. Among physicians who referred ≥5 patients, the yield ranged from 0% to 80% (p < 0.0001).

Conclusions

In this large cohort of unrelated patients referred for LQTS genetic testing, the clinical phenotype strongly correlated with the likelihood of elucidating a pathogenic mutation with the cardiac channel gene screen.

Abbreviations and Acronyms

LQTS
long QT syndrome
QTc
corrected QT interval

Cited by (0)

Dr. Ackerman’s Sudden Death Genomics Laboratory is supported by a Mayo Foundation Clinician Research award, the CJ Foundation for SIDS, a clinical scientist development award from the Doris Duke Charitable Foundation, and the National Institutes of Health (HD42569). Dr. Ackerman is an established investigator of the American Heart Association. Dr. Ackerman is a consultant and scientific advisory board member for Genaissance Pharmaceuticals that has released the Familion genetic test for cardiac ion channel abnormalities. However, Genaissance Pharmaceuticals provided no financial support for this study. The first two authors contributed equally to this article.