Swimming, a gene-specific arrhythmogenic trigger for inherited long QT syndrome.
OBJECTIVE
To determine the genetic basis for long QT syndrome (LQTS) in a cohort of patients with a personal history or an extended family history of a swimming-triggered cardiac event.


METHODS
After review of the Mayo Clinic unit medical record system, blood samples or archived autopsy tissue samples were obtained from a retrospective cohort of 35 cases diagnosed as having autosomal dominant LQTS. Exon-specific amplification by polymerase chain reaction and direct sequence analyses were performed on the entire KVLQT1 gene.


RESULTS
Six cases had a personal history or an extended family history of a near drowning or drowning. In all 6 cases, LQTS-causing mutations in KVLQT1 gene were identified: 3 deletion mutations, 2 donor splice site mutations, and 1 missense mutation. One of the mutations, a novel donor splicing defect, was determined by postmortem molecular analysis of a paraffin-embedded tissue block from a 12-year-old girl who died in 1976. Distinct KVLQT1 mutations were demonstrated in 3 of the remaining 29 cases. The overall frequency of KVLQT1 defects in LQTS was 100% (6/6) in those with and 10% (3/29) in those without a personal history or an extended family history of drowning or near drowning (P<.001).


CONCLUSIONS
Swimming appears to be a gene-specific (KVLQT1) arrhythmogenic trigger for LQTS. This study provides proof of principle that an unexplained drowning or near drowning may have a genetic basis.
Ackerman
M J
MJ
Department of Pediatric and Adolescent Medicine, Mayo Clinic Rochester, Minn 55905, USA.
Tester
D J
DJ
Porter
C J
CJ
D000293:Adolescent; D000328:Adult; D002648:Child; D004332:Drowning / Q000235:genetics*; D005260:Female; D006801:Humans; D008133:Long QT Syndrome / Q000235:genetics*; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D013550:Swimming