title: Mortality risk of untreated myosin-binding protein C-related hypertrophic cardiomyopathy: insight into the natural history.
abstract: OBJECTIVE
  The goal of this study was to assess the mortality of hypertrophic cardiomyopathy (HCM), partly in times when the disease was not elucidated and patients were untreated.
  
  
  BACKGROUND
  HCM is feared for the risk of sudden cardiac death (SCD). Insight in the natural history of the disorder is needed to design proper screening strategies for families with HCM.
  
  
  METHODS
  In 6 large, 200-year multigenerational pedigrees (identified by using genealogical searches) and in 140 small (contemporary) pedigrees (first-degree relatives of the proband) with HCM caused by a truncating mutation in the myosin-binding protein C gene (n = 1,118), we determined all-cause mortality using the family tree mortality ratio method. The study's main outcome measure was the standardized mortality ratio (SMR).
  
  
  RESULTS
  In the large pedigrees, overall mortality was not increased (SMR 0.86 [95% confidence interval (CI): 0.72 to 1.03]), but significant excess mortality occurred between 10 and 19 years (SMR 2.7 [95% CI: 1.2 to 5.2]). In the small families, the SMR was increased (SMR 1.5 [95% CI: 1.3 to 1.6]) [corrected] and excess mortality was observed between 10 and 39 years (SMR 3.2 [95% CI: 2.3 to 4.3]) and 50 and 59 years (SMR 1.9 [95% CI: 1.4 to 2.5]).
  
  
  CONCLUSIONS
  We identified specific age categories with increased mortality risks in HCM families. The small, referred pedigrees had higher mortality risks than the large 200-year multigenerational pedigrees. Our findings support the strategy of starting cardiological and genetic screening in the first-degree relatives of a proband from 10 years onward and including persons in the screening at least until the age of 60 years. Screening of more distant relatives is probably most efficient between 10 and 19 years.
authors: Department of Clinical Genetics, Academic Medical Center, Amsterdam, the Netherlands.
authors: Eline A
authors: EA
authors: Nannenberg
authors: Michelle
authors: M
authors: Michels
authors: Imke
authors: I
authors: Christiaans
authors: Danielle
authors: D
authors: Majoor-Krakauer
authors: Yvonne M
authors: YM
authors: Hoedemaekers
authors: J Peter
authors: JP
authors: van Tintelen
authors: M Paola
authors: MP
authors: Lombardi
authors: Folkert J
authors: FJ
authors: ten Cate
authors: Arend F L
authors: AF
authors: Schinkel
authors: Jan G P
authors: JG
authors: Tijssen
authors: Irene M
authors: IM
authors: van Langen
authors: Arthur A M
authors: AA
authors: Wilde
authors: Eric J G
authors: EJ
authors: Sijbrands
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D002312:Cardiomyopathy, Hypertrophic / Q000097:blood / Q000235:genetics / Q000401:mortality*; D002352:Carrier Proteins / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009218:Myosins; D010375:Pedigree; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods*; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D055815:Young Adult; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D009218:Myosins; D000099163:Myosin Binding Protein C