TY - JOUR T1 - Catecholaminergic polymorphic ventricular tachycardia: RYR2 mutations, bradycardia, and follow up of the patients JF - Journal of Medical Genetics JO - J Med Genet SP - 863 LP - 870 DO - 10.1136/jmg.2004.028993 VL - 42 IS - 11 AU - A V Postma AU - I Denjoy AU - J Kamblock AU - M Alders AU - J-M Lupoglazoff AU - G Vaksmann AU - L Dubosq-Bidot AU - P Sebillon AU - M M A M Mannens AU - P Guicheney AU - A A M Wilde Y1 - 2005/11/01 UR - http://jmg.bmj.com/content/42/11/863.abstract N2 - Background: The aim of the study was to assess underlying genetic cause(s), clinical features, and response to therapy in catecholaminergic polymorphic ventricular tachycardia (CPVT) probands. Methods and results: We identified 13 missense mutations in the cardiac ryanodine receptor (RYR2) in 12 probands with CPVT. Twelve were new, of which two are de novo mutations. A further 11 patients were silent gene carriers, suggesting that some mutations are associated with low penetrance. A marked resting sinus bradycardia off drugs was observed in all carriers. On β blocker treatment, 98% of the RYR2 mutation carriers remained symptom free with a median follow up of 2 (range: 2–37) years. Conclusion: CPVT patients with RYR2 mutation have bradycardia regardless of the site of the mutation, which could direct molecular diagnosis in (young) patients without structural heart disease presenting with syncopal events and a slow heart rate but with normal QTc at resting ECG. Treatment with β blockers has been very effective in our CPVT patients during initial or short term follow up. Given the risk of sudden death and the efficacy of β blocker therapy, the identification of large numbers of RYR2 mutations thus calls for genetic screening, early diagnosis, and subsequent preventive strategies. ER -