Coinheritance of Hypertrophic and Arrhythmogenic Cardiomyopathy Variants in a Patient With Hypertrophic Cardiomyopathy

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 (MYH7 p.Glu924Lys) and plakophilin 2 (PKP2 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.