title: Screening for ryanodine receptor type 2 mutations in families with effort-induced polymorphic ventricular arrhythmias and sudden death: early diagnosis of asymptomatic carriers.
abstract: OBJECTIVE
  We sought to establish the role of genetic screening for ryanodine receptor type 2 (RyR2) gene mutations in families with effort-induced polymorphic ventricular arrhythmia (PVA), syncope and juvenile sudden death.
  
  
  BACKGROUND
  The RyR2 mutations have been associated with PVA, syncope and sudden death in response to physical or emotional stress.
  
  
  METHODS
  We studied 81 subjects (39 males and 42 females; mean age 31 +/- 20 years) belonging to eight families with pathogenic RyR2 mutations. All subjects underwent screening for RyR2 mutations, electrocardiography (ECG), 24-h Holter monitoring, signal-averaged electrocardiography (SAECG), two-dimensional echocardiography and exercise stress testing. Electrophysiologic (EP) study was performed in nine patients.
  
  
  RESULTS
  Six different RyR2 mutations were found in eight families. Forty-three family members carried the gene mutation. Of these, 28 (65%) showed effort-induced arrhythmic symptoms or signs and one died suddenly during follow-up. Family history revealed 19 juvenile cases of sudden death during effort or emotion. In two families sharing the same mutation, no subject presented with PVA during the stress test; thus, sudden death and syncope were the only clinical manifestations. The 12-lead ECG was normal in all but two subjects, whereas five patients showed positive late potentials on the SAECG. In 17 (39.5%) of 43 subjects, the two-dimensional echocardiogram revealed localized kinetic abnormalities and mild structural alterations of the right ventricle. The EP study was not able to induce PVA.
  
  
  CONCLUSIONS
  The absence of symptoms and PVA on the stress test in more than one-third of carriers of RyR2 mutations, as well as the lack of PVA inducibility by the EP study, underlies the importance of genetic screening for the early diagnosis of asymptomatic carriers and prevention of sudden death.
authors.affiliation: Department of Cardiology, University of Padua Medical School, Via A. Gabelli, 86-35121 Padua, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bauce
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rampazzo
authors.forename: Cristina
authors.initials: C
authors.lastname: Basso
authors.forename: Alessia
authors.initials: A
authors.lastname: Bagattin
authors.forename: Luciano
authors.initials: L
authors.lastname: Daliento
authors.forename: Natascia
authors.initials: N
authors.lastname: Tiso
authors.forename: Pietro
authors.initials: P
authors.lastname: Turrini
authors.forename: Gaetano
authors.initials: G
authors.lastname: Thiene
authors.forename: Gian Antonio
authors.initials: GA
authors.lastname: Danieli
authors.forename: Andrea
authors.initials: A
authors.lastname: Nava
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004452:Echocardiography; D004562:Electrocardiography; D015716:Electrocardiography, Ambulatory; D005080:Exercise Test; D005260:Female; D005820:Genetic Testing; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D012815:Signal Processing, Computer-Assisted; D013575:Syncope / Q000235:genetics; D017180:Tachycardia, Ventricular / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel