A case of arrhythmic cardiomyopathy caused by rare multiple gene mutations

TL;DR

This paper reports a rare case of arrhythmic cardiomyopathy caused by multiple gene mutations in a patient and their family.

Contribution

The study presents a unique case of ACM with three rare genetic variants in both desmosomal and non-desmosomal proteins.

Findings

The patient had biventricular ACM with three rare genetic variants.

Phenotypic differences were observed among family members with the same genetic variants.

The case highlights the need for personalized management and genetic counseling in ACM.

Abstract

Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiomyopathy characterized by a high risk of ventricular tachycardia and sudden cardiac death, often involving the right ventricle or both ventricles, with the initial onset usually in adolescence or young adulthood, and most cases can be diagnosed before the age of 40 years. Studies have shown that ACM is often caused by mutations in genes encoding desmosomal proteins, with a small proportion caused by mutations in nonencoding desmosomal proteins. In this paper, we report a patient with biventricular arrhythmogenic cardiomyopathy who presented with recurrent syncope, paroxysmal ventricular tachycardia, and heart failure in old age. Genetic testing revealed that the patient (proband) carried three rare genetic variants in the genes encoding desmosomal and nondesmosomal proteins at the same time. No relevant reports were found in the literature review, and the phenotypic penetrance age differences among family members carrying the same genetic variant were also large, further indicating the complexity of ACM genotype–phenotype expression. We treated the family members for one year of follow-up. To provide more references for risk assessment, individualized management and genetic counselling of ACM patients are needed.

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