Unexplained Drownings and the Cardiac Channelopathies: A Molecular Autopsy Series

October 2011
Mayo Clinic Proceedings;Oct2011, Vol. 86 Issue 10, p941
Academic Journal
OBJECTIVE: To determine the prevalence and spectrum of mutations associated with long QT syndrome (LQTS) and catecholamin- ergic polymorphic ventricular tachycardia (CPVT) In a seemingly unexplained drowning cohort. PATIENTS AND METHODS: From September 1, 1998, through October 31, 2010, 35 unexplained drowning victims (23 male and 12 female; mean ± SD age, 17±12 years [range, 4-69 years]) were referred for a cardiac channel molecular autopsy. Of these, 28 (20 male and 8 female) drowned while swimming, and 7 (3 male and 4 female) were bathtub submersions. Polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing were used for a comprehensive mutational analy- sis of the 3 maJor LQTS-susceptibility genes (KCNQ1, KCNH2, and SCN5A), and a targeted analysis of the CPVT1-associated, RYR2- encoded cardiac ryanodine receptor was conducted. RESULTS: Of the 28 victIms of swimming-related drowning, 8 (28.6%) were mutation positive, Including 2 wIth KCNQ1 mutations (L273F, AAPdeI7I-73 plus V524G) and 6 wIth RYR2 muta- tions (R414C, 1419F, Ri.013Q, V2321A, R2401H, and V2475F). None of the bathtub victims were mutation positive. Of the 28 victims who drowned while swimming, women were more likely to be mutation positive than men (5/8 [62.5%] vs 3/20 [15%); P~.O2). Although none of the mutation-positive, swimming-related drowning victims had a premortem diagnosis of LQTS or CPVT, a family history of cardiac arrest, family history of prior drowning, or QT prolongation was present in 50%. CONCLUSION: Nearly 30% of the victims of swimming-related drown- ing hosted a cardiac channel mutation. Genetic testing should be considered in the postmortem evaluation of an unexplained drown- ing, especially if a positive personal or family history is elicited.


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