Spectrum and frequency of cardiac channel defects in swimming-triggered arrhythmia syndromes.
BACKGROUND
Swimming is a relatively genotype-specific arrhythmogenic trigger for type 1 long-QT syndrome (LQT1). We hypothesize that mimickers of concealed LQT1, namely catecholaminergic polymorphic ventricular tachycardia (CPVT), may also underlie swimming-triggered cardiac events.


RESULTS
Between August 1997 and May 2003, 388 consecutive, unrelated patients were referred specifically for LQTS genetic testing. The presence of a personal and/or family history of a near-drowning or drowning was determined by review of the medical records and/or phone interviews and was blinded to genetic test results. Comprehensive mutational analysis of the 5 LQTS-causing channel genes, KCNQ1 (LQT1), KCNH2 (LQT2), SCN5A (LQT3), KCNE1 (LQT5), and KCNE2 (LQT6), along with KCNJ2 (Andersen-Tawil syndrome) and targeted analysis of 18 CPVT1-associated exons in RyR2, was performed with the use of denaturing high-performance liquid chromatography and direct DNA sequencing. Approximately 11% (43 of 388) of the index cases had a positive swimming phenotype. Thirty-three of these 43 index cases had a "Schwartz" score (> or =4) suggesting high clinical probability of LQTS. Among this subset, 28 patients (85%) were LQT1, 2 patients (6%) were LQT2, and 3 were genotype negative. Among the 10 cases with low clinical probability for LQTS, 9 had novel, putative CPVT1-causing RyR2 mutations.


CONCLUSIONS
In contrast to previous studies that suggested universal LQT1 specificity, genetic heterogeneity underlies channelopathies that are suspected chiefly because of a near-drowning or drowning. CPVT1 and strategic genotyping of RyR2 should be considered when LQT1 is excluded in the pathogenesis of a swimming-triggered arrhythmia syndrome.
Choi
Grace
G
Department of Pediatric and Adolescent Medicine/Division of Cardiovascular Disease, Mayo Clinic College of Medicine, Rochester, Minn, USA.
Kopplin
Laura J
LJ
Tester
David J
DJ
Will
Melissa L
ML
Haglund
Carla M
CM
Ackerman
Michael J
MJ
D000293:Adolescent; D000328:Adult; D002648:Child; D004252:DNA Mutational Analysis; D004332:Drowning; D005145:Face; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007101:Immersion / Q000009:adverse effects; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008133:Long QT Syndrome / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008958:Models, Molecular; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel; D015701:Near Drowning; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D016037:Single-Blind Method; D015222:Sodium Channels / Q000235:genetics; D013550:Swimming; D017180:Tachycardia, Ventricular / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology
C489622:KCNE1 protein, human; C489619:KCNE2 protein, human; C502068:KCNE5 protein, human; C489457:KCNJ2 protein, human; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; C489610:KCNV2 protein, human; D062554:NAV1.5 Voltage-Gated Sodium Channel; D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated; D019837:Ryanodine Receptor Calcium Release Channel; C568320:SCN5A protein, human; D015222:Sodium Channels