title: Penetrance of hypertrophic cardiomyopathy in children and adolescents: a 12-year follow-up study of clinical screening and predictive genetic testing.
abstract: BACKGROUND
  The penetrance of hypertrophic cardiomyopathy (HCM) during childhood and adolescence has been only sparsely described. We studied the penetrance of HCM and the short- and long-term outcomes of clinical screening and predictive genetic testing of child relatives of patients with HCM.
  
  
  RESULTS
  Ninety probands and 361 relatives were included in a family screening program for HCM (1994-2001). Eleven sarcomere genes, CRYAB, α-GAL, and titin were screened. Sixty-six relatives and 4 probands were <18 years of age at inclusion. Twelve child relatives were mutation carriers (age, 12 ± 5 years), and 26 had unknown genetic status, ie, relatives from families without identified mutations (n = 21) or not tested (n = 5) (age, 11 ± 5 years). Twenty-eight noncarriers (42%; age, 10 ± 4 years) served as control subjects. Two of 38 child relatives (5%) at risk of developing HCM fulfilled diagnostic criteria for HCM at inclusion. After 12 ± 1 years of follow-up, 2 of the 36 (6%; 95% confidence interval, 2-18) at-risk child relatives who were phenotype negative at inclusion had developed the HCM phenotype at 26 and 28 years of age. During follow-up, none of the child relatives experienced serious cardiac events. Participation in the screening program had no long-term negative psychological impact.
  
  
  CONCLUSIONS
  The penetrance of HCM in phenotype-negative child relatives at risk of developing HCM was 6% after 12 years of follow-up. The finding of phenotype conversion in the mid-20s warrants continued screening into adulthood. Forty-two percent of the child relatives were noncarriers, and repeat clinical follow-up could be safely limited to the remaining children.
authors.affiliation: Unit for Inherited Heart Diseases, Heart Center, National University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. mortenjensen@dadlnet.dk
authors.forename: Morten K
authors.initials: MK
authors.lastname: Jensen
authors.forename: Ole
authors.initials: O
authors.lastname: Havndrup
authors.forename: Michael
authors.initials: M
authors.lastname: Christiansen
authors.forename: Paal S
authors.initials: PS
authors.lastname: Andersen
authors.forename: Birgitte
authors.initials: B
authors.lastname: Diness
authors.forename: Anna
authors.initials: A
authors.lastname: Axelsson
authors.forename: Flemming
authors.initials: F
authors.lastname: Skovby
authors.forename: Lars
authors.initials: L
authors.lastname: Køber
authors.forename: Henning
authors.initials: H
authors.lastname: Bundgaard
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000235:genetics*; D002648:Child; D004452:Echocardiography; D004562:Electrocardiography; D005190:Family; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D006579:Heterozygote; D006801:Humans; D019683:Penetrance; D010641:Phenotype; D011237:Predictive Value of Tests; D012307:Risk Factors; D012518:Sarcomeres / Q000235:genetics