Development of left ventricular hypertrophy in adults with hypertrophic cardiomyopathy caused by cardiac myosin-binding protein C gene mutations
Development of left ventricular hypertrophy in adults with hypertrophic cardiomyopathy caused by cardiac myosin-binding protein C gene mutations
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DOI：
10.1016/s0735-1097(01)01386-9
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发表时间：
2001-08-01
影响因子：
24
通讯作者：
Seidman, CE
中科院分区：
文献类型：
--
作者：
Maron, BJ;Niimura, H;Seidman, CE
目的探讨肥厚型心肌病（HCM）的遗传易感性亲属是否在成年期发生左心室肥厚（LVH）。心肌肌球蛋白结合蛋白C（MyBPC）基因突变与年龄相关性心肌肥厚有关。方法采用超声心动图和12导联心电图对7个HCM家系中MyBPC基因突变引起的表型表达进行研究，以进一步分析HCM患者左室肥厚的休眠状态。包括21名遗传影响的亲属（34%），他们不表达HCM形态学表型（由于显示正常的左心室壁厚度）。在这21个表型阴性的个体中，9个是儿童，大概处于肥大前期，12个是成人。在12例正常室壁厚度小于或等于12 mm的成人中（7例心电图正常），5例随后前瞻性地进行了4 - 6年的系列超声心动图检查。值得注意的是，这五个成年人中的三个显示出发展LVH的中年，出现在第一次在33，34和42岁，分别与流出道梗阻或显着symptoms.Conclusions在成人HCM，致病MyBPC突变并不罕见与左室肥厚的超声心动图。本研究首次在前瞻性连续超声心动图的个体患者中证实了延迟性重塑伴LVH的发展，并在成年期重新出现，证实了HCM中MyBPC突变与年龄相关的突变原则。这些观察结果改变了关于HCM临床谱和家族筛查策略的普遍看法，并进一步表征了这种疾病中LVH的演变。（美国科尔心脏病学杂志2001;38：315-21）（C）2001年美国心脏病学会。
Objectives We sought to determine whether the development of left ventricular hypertrophy (LVH) can be demonstrated during adulthood in genetically affected relatives with hypertrophic cardiomyopathy (HCM).Background Hypertrophic cardiomyopathy is a heterogeneous cardiac disease caused by mutations in nine genes drat encode proteins of the sarcomere. Mutations in cardiac myosin-binding protein C (MyBPC) gene have been associated with age-related penetrance.Methods To further analyze dormancy of LVH in patients with HCM, we studied, using echocardiography and 12-lead electrocardiography, the phenotypic expression caused by MyBPC mutations in seven genotyped pedigrees.Results Of 119 family members studied, 61 were identified with a MyBPC mutation, including 21 genetically affected relatives (34%) who did not express the HCM morphologic phenotype (by virtue of showing normal left ventricular wall thickness). Of these 21 phenotype-negative individuals, 9 were children, presumably in the prehypertrophic phase, and 12 were adults. Of the 12 adults with normal wall thickness less than or equal to 12 mm (7 also with normal electrocardiograms), 5 subsequently underwent serial echocardiography prospectively over four to six years. Of note, three of these five adults showed development of LVH in mid-life, appearing for the first time at 33, 34 and 42 years of age, respectively, not associated with outflow obstruction or significant symptoms.Conclusions In adults with HCM, disease-causing MyBPC mutations are not uncommonly associated with absence of LVH on echocardiogram. Delayed remodeling with the development of LVH appearing de novo in adulthood, demonstrated here for the first time in individual patients with prospectively obtained serial echocardiograms, substantiates the principle of age-related penetrance for MyBPC mutations in HCM. These observations alter prevailing perceptions regarding the HCM clinical spectrum and family screening strategies and further characterize the evolution of LVH in this disease. (J Am Coll Cardiol 2001;38:315-21) (C) 2001 by the American College of Cardiology.