Spectrum and frequency of cardiac channel defects in swimming-triggered arrhythmia syndromes.

Abstract

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.

METHODS AND 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.

• Authors: Grace Choi, Laura J Kopplin, David J Tester, Melissa L Will, Carla M Haglund, Michael J Ackerman
• Journal: Circulation (Circulation) Vol. 110 Issue 15 Pg. 2119-24 (Oct 12 2004) ISSN: 1524-4539 [Electronic] United States
• PMID: 15466642 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• KCNE1 protein, human
• KCNE2 protein, human
• KCNE5 protein, human
• KCNJ2 protein, human
• KCNQ Potassium Channels
• KCNQ1 Potassium Channel
• KCNQ1 protein, human
• KCNV2 protein, human
• NAV1.5 Voltage-Gated Sodium Channel
• Potassium Channels, Inwardly Rectifying
• Potassium Channels, Voltage-Gated
• Ryanodine Receptor Calcium Release Channel
• SCN5A protein, human
• Sodium Channels

Topics

• Adolescent
• Adult
• Child
• DNA Mutational Analysis
• Drowning
• Face
• Female
• Genetic Predisposition to Disease
• Genotype
• Humans
• Immersion (adverse effects)
• KCNQ Potassium Channels
• KCNQ1 Potassium Channel
• Long QT Syndrome (etiology, genetics, physiopathology)
• Male
• Models, Molecular
• Mutation
• NAV1.5 Voltage-Gated Sodium Channel
• Near Drowning
• Potassium Channels, Inwardly Rectifying (genetics)
• Potassium Channels, Voltage-Gated (genetics)
• Ryanodine Receptor Calcium Release Channel (genetics)
• Single-Blind Method
• Sodium Channels (genetics)
• Swimming
• Tachycardia, Ventricular (etiology, genetics, physiopathology)