title: The yield of risk stratification for sudden cardiac death in hypertrophic cardiomyopathy myosin-binding protein C gene mutation carriers: focus on predictive screening.
abstract: OBJECTIVE
  We investigated the presence of a clinical diagnosis of hypertrophic cardiomyopathy (HCM) and of risk factors for sudden cardiac death (SCD) at the first cardiological evaluation after predictive genetic testing in asymptomatic carriers of an MYBPC3 gene mutation.
  
  
  RESULTS
  Two hundred and thirty-five mutation carriers were cardiologically evaluated on the presence of HCM and risk factors. A clinical diagnosis of HCM was made in 53 carriers (22.6%). Disease penetrance at 65 years was incomplete for all types of MYBPC3 gene mutations. Women were affected less often than men (15 and 32% respectively, P = 0.003) and disease penetrance was lower in females than in males (13 and 30% at 50 years, respectively, P = 0.024). One risk factor was present in 87 carriers and 9 had two or more risk factors. Twenty-five carriers (11%) with one or more risk factors and manifest HCM could be at risk for SCD.
  
  
  CONCLUSIONS
  At first cardiological evaluation almost one-quarter of asymptomatic carriers was diagnosed with HCM. Risk factors for SCD were frequently present and 11% of carriers could be at risk for SCD. Predictive genetic testing in HCM families and frequent cardiological evaluation on the presence of HCM and risk factors for SCD are justified until advanced age.
authors.affiliation: Department of Clinical Genetics, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Imke
authors.initials: I
authors.lastname: Christiaans
authors.forename: Erwin
authors.initials: E
authors.lastname: Birnie
authors.forename: Irene M
authors.initials: IM
authors.lastname: van Langen
authors.forename: Karin Y
authors.initials: KY
authors.lastname: van Spaendonck-Zwarts
authors.forename: J Peter
authors.initials: JP
authors.lastname: van Tintelen
authors.forename: Maarten P
authors.initials: MP
authors.lastname: van den Berg
authors.forename: Douwe E
authors.initials: DE
authors.lastname: Atsma
authors.forename: Apollonia T J M
authors.initials: AT
authors.lastname: Helderman-van den Enden
authors.forename: Yigal M
authors.initials: YM
authors.lastname: Pinto
authors.forename: J F
authors.initials: JF
authors.lastname: Hermans-van Ast
authors.forename: Gouke J
authors.initials: GJ
authors.lastname: Bonsel
authors.forename: Arthur A M
authors.initials: AA
authors.lastname: Wilde
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D016757:Death, Sudden, Cardiac / Q000517:prevention & control*; D005260:Female; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D019683:Penetrance; D018570:Risk Assessment; D012307:Risk Factors; D055815:Young Adult; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D000099163:Myosin Binding Protein C