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.

译文

背景:在儿童和青少年时期肥厚型心肌病(HCM)的渗透率仅得到了很少的描述。我们研究了HCM的渗透率以及HCM患者的儿童亲属的临床筛查和预测性基因检测的短期和长期结果。
方法与结果:1994年至2001年,在HCM家庭筛查计划中纳入了90名先证者和361名亲属。筛选了11个肌小节基因CRYAB,α-GAL和titin。六十六名亲戚和四名先证者年龄小于18岁。十二名儿童亲属是突变携带者(年龄为12±5岁),有26名遗传状况未知,即来自未发现突变的家庭的亲属(n = 21)或未经测试(n = 5)(年龄为11±5岁) )。对照组为28名非携带者(42%;年龄为10±4岁)。 38名患HCM的儿童亲属中有2名(5%)符合入选HCM的诊断标准。经过12±1年的随访,在纳入时表现型为阴性的36名高危儿童亲戚中,有2名(6%; 95%置信区间为2-18)在26岁和28岁时出现了HCM表型。 。在随访期间,没有任何一个儿童亲属经历过严重的心脏事件。参与筛查程序不会对心理产生长期负面影响。
结论:随访12年后,表型阴性儿童亲属中HCM的外显率为6%。在20年代中期发现表型转化的情况值得继续筛选,直至成年。 42%的儿童亲属是非携带者,重复进行的临床随访可以安全地限于其余儿童。

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