Original ArticleSwimming, a Gene-Specific Arrhythmogenic Trigger for Inherited Long QT Syndrome
Section snippets
Identification of a Swimming-Triggered LQTS Cohort
Thirty-nine probable cases of autosomal dominant LQTS were identified by review of the unit medical record system from 1975 to 1999. The Mayo Clinic unit medical record contains details of every outpatient visit to a physician's office or emergency department, every inpatient hospitalization, every laboratory result, all pathology reports, and all patient correspondence. In addition to the 2 near-drowning cases previously reported,13,14 review of the medical records as well as follow-up
Results
Every case of autosomal dominant LQTS with a personal history or an extended family history of drowning or near drowning had mutations in KVLQT1 (6/6; P<.001). Figure 1 summarizes some of the phenotypic information pertaining to this swimming cohort, including the 2 previously reported cases (numbered cases 1 and 5 herein). The specific LQTS mutations discovered in 5 of the 6 cases have been reported previously in other families with LQTS.13,14,18-21 A novel splice-site mutation was identified
Discussion
Less than 50% of LQTS is accounted for by mutations in the 5 cardiac ion channel genes, with mutations in the KVLQT1 gene being most common for these genotyped LQTS cases. However, only one fifth of all LQTS stems from a defective KVLQT1 substrate (P. J. Schwartz, MD, oral communication, October 1, 1999). There are obvious limitations in this assignment of LQTS disease gene frequencies, since the denominator of patients who have LQTS either manifest clinically or concealed genetically is
Acknowledgments
The authors wish to thank Carla M. Bell for her assistance with the chart reviews and to Erik J. Bergstralh for his statistical analysis. Moreover, we are indebted to these families with LQTS for their willingness to participate in this project. We hope that advances in our understanding of LQTS made possible by their involvement will prevent future tragedies such as those described herein.
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Dr Ackerman was supported by a Howard W. Siebens Molecular Medicine Award from the Mayo Foundation and a Mayo Foundation clinical research award.