TY - JOUR
T1 - Penetrance of Hypertrophic Cardiomyopathy in Children and Adolescents
T2 - A 12-Year Follow-up Study of Clinical Screening and Predictive Genetic Testing
AU - Jensen, Morten K
AU - Havndrup, Ole
AU - Christiansen, Michael
AU - Andersen, Paal S
AU - Diness, Birgitte
AU - Axelsson, Anna
AU - Skovby, Flemming
AU - Køber, Lars
AU - Bundgaard, Henning
PY - 2013/1/1
Y1 - 2013/1/1
N2 - 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. Methods and 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.
AB - 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. Methods and 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.
U2 - 10.1161/CIRCULATIONAHA.111.090514
DO - 10.1161/CIRCULATIONAHA.111.090514
M3 - Journal article
C2 - 23197161
SN - 0009-7322
VL - 127
SP - 48
EP - 54
JO - Circulation
JF - Circulation
ER -