Circulation：肥厚性心肌病遗传外显率调查

The penetrance of hypertrophic cardiomyopathy (HCM) during childhood and adolescence has only been 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 to patients with HCM.

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 four probands were <18 years of age at inclusion. Twelve child relatives were mutation carriers (age 12±5 years), and 26 had unknown genetic status, i.e. relatives from families without identified mutations (n=21) or not tested (n=5) (age 11±5 years). Twenty-eight (42%) non-carriers (age 10±4 years) served as controls. Two out of 38 (5%) child relatives at risk of developing HCM fulfilled diagnostic criteria for HCM at inclusion. After 12±1 years follow-up two out of the 36 (6%, CI 2-18%) at risk child relatives, who were phenotype-negative at inclusion, had developed the HCM phenotype at the age of 26 and 28 years. During follow-up none of the child relatives experienced serious cardiac events. Participation in the screening program had no long-term negative psychological impact.

The penetrance of HCM in phenotype-negative child relatives at risk of developing HCM was 6% after 12 years follow-up. The finding of phenotype conversion in the mid-twenties warrants continued screening to extend into adulthood. Forty-two percent of the child relatives were non-carriers, and repeated clinical follow-up could safely be limited to the remaining children.