Lee Yi Siang, Pua Chee Jian, Bylstra Yasmin, Shekhar Jamuar Saumya, Devi Balakrishnan Iswaree
Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
National Heart Research Institute Singapore, National Heart Centre Singapore.
JACC Case Rep. 2024 Nov 20;29(22):102646. doi: 10.1016/j.jaccas.2024.102646.
Hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC) are phenotypically distinct inherited cardiac diseases. This case report presents a woman aged 51 years with coinheritance of pathogenic/likely pathogenic variants of the β-myosin heavy chain ( p.Glu924Lys) and plakophilin 2 ( p.Leu442Argfs∗5), each implicated in HCM and ARVC, respectively. Interestingly, she exhibits the classic HCM phenotype with a heavy arrhythmic burden but no diagnostic features of ARVC. The coinheritance of disease-causing variants in cardiomyopathies has been posited to result in an earlier disease onset and more aggressive clinical course. However, such a relationship has yet to be established when the variants are each robustly associated with different cardiomyopathy phenotypes. The limited existing literature on such cases paints a heterogenous picture of clinical phenotypes with no obvious trend. Here, we explore the interplay between coinheritance of disease-causing variants and resultant disease manifestation, particularly in the context of cardiomyopathies.
肥厚型心肌病（HCM）和致心律失常性右室心肌病（ARVC）是表型不同的遗传性心脏疾病。本病例报告介绍了一位51岁女性，她同时遗传了β-肌球蛋白重链（p.Glu924Lys）和盘状球蛋白2（p.Leu442Argfs∗5）的致病/可能致病变异，这两种变异分别与HCM和ARVC相关。有趣的是，她表现出典型的HCM表型，心律失常负担较重，但没有ARVC的诊断特征。心肌病中致病变异的共同遗传被认为会导致疾病更早发作和临床病程更具侵袭性。然而，当这些变异分别与不同的心肌病表型密切相关时，这种关系尚未得到证实。关于此类病例的现有文献有限，描绘出的临床表型各异，没有明显趋势。在此，我们探讨致病变异的共同遗传与由此产生的疾病表现之间的相互作用，特别是在心肌病的背景下。
