title: Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia.
abstract: BACKGROUND
  Mutations in the cardiac ryanodine receptor gene (RyR2) underlie catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited arrhythmogenic disease occurring in the structurally intact heart. The proportion of patients with CPVT carrying RyR2 mutations is unknown, and the clinical features of RyR2-CPVT as compared with nongenotyped CPVT are undefined.
  
  
  RESULTS
  Patients with documented polymorphic ventricular arrhythmias occurring during physical or emotional stress with a normal heart entered the study. The clinical phenotype of the 30 probands and of 118 family members was evaluated, and mutation screening on the RyR2 gene was performed. Arrhythmias documented in probands were: 14 of 30 bidirectional ventricular tachycardia, 12 of 30 polymorphic ventricular tachycardia, and 4 of 30 catecholaminergic idiopathic ventricular fibrillation; RyR2 mutations were identified in 14 of 30 probands (36% bidirectional ventricular tachycardia, 58% polymorphic ventricular tachycardia, 50% catecholaminergic idiopathic ventricular fibrillation) and in 9 family members (4 silent gene carriers). Genotype-phenotype analysis showed that patients with RyR2 CPVT have events at a younger age than do patients with nongenotyped CPVT and that male sex is a risk factor for syncope in RyR2-CPVT (relative risk=4.2).
  
  
  CONCLUSIONS
  CPVT is a clinically and genetically heterogeneous disease manifesting beyond pediatric age with a spectrum of polymorphic arrhythmias. beta-Blockers reduce arrhythmias, but in 30% of patients an implantable defibrillator may be required. Genetic analysis identifies two groups of patients: Patients with nongenotyped CPVT are predominantly women and become symptomatic later in life; patients with RyR2 CPVT become symptomatic earlier, and men are at higher risk of cardiac events. These data provide a rationale for prompt evaluation and treatment of young men with RyR2 mutations.
authors.affiliation: Molecular Cardiology, IRCCS Fondazione S. Maugeri, University of Pavia, Pavia, Italy. spriori@fsm.it
authors.forename: Silvia G
authors.initials: SG
authors.lastname: Priori
authors.forename: Carlo
authors.initials: C
authors.lastname: Napolitano
authors.forename: Mirella
authors.initials: M
authors.lastname: Memmi
authors.forename: Barbara
authors.initials: B
authors.lastname: Colombi
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Drago
authors.forename: Maurizio
authors.initials: M
authors.lastname: Gasparini
authors.forename: Luciano
authors.initials: L
authors.lastname: DeSimone
authors.forename: Fernando
authors.initials: F
authors.lastname: Coltorti
authors.forename: Raffaella
authors.initials: R
authors.lastname: Bloise
authors.forename: Roberto
authors.initials: R
authors.lastname: Keegan
authors.forename: Fernando E S
authors.initials: FE
authors.lastname: Cruz Filho
authors.forename: Gabriele
authors.initials: G
authors.lastname: Vignati
authors.forename: Abraham
authors.initials: A
authors.lastname: Benatar
authors.forename: Angelica
authors.initials: A
authors.lastname: DeLogu
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D002395:Catecholamines; D002648:Child; D002675:Child, Preschool; D016757:Death, Sudden, Cardiac / Q000453:epidemiology; D005192:Family Health; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D016415:Sequence Alignment; D015996:Survival Rate; D017180:Tachycardia, Ventricular / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000628:therapy
chemical_list: D002395:Catecholamines; D019837:Ryanodine Receptor Calcium Release Channel