Hypertrophic Phenotype in an Adolescent from the Amazon Region Associated with Combined Variants in the GLA, TTR, and PRKAG2 genes

Introduction

Hypertrophic cardiomyopathy (HCM) phenotype is defined as increased wall thickness of the left and/or right ventricle without loading conditions that explain this. Its diagnosis is confirmed by imaging tests such as echocardiogram and cardiac magnetic resonance (CMR) with the presence of wall thickness ≥ 15 mm in any myocardial segment or 13 mm in first-grade relatives of patients with a confirmed diagnosis. The most common cause of this phenotype is genetic HCM caused by mutations in genes encoding sarcomeric proteins. Most patients with HCM are asymptomatic, but some patients may present significant symptoms, and this is an important cause of sudden death in young people. However, it is important to consider other conditions known as phenocopies because they may have similar characteristics in imaging tests, but with specific etiologies that have different pathophysiological mechanisms. Among these phenocopies, we highlight mitochondrial diseases, RASopathies, muscular dystrophies, PRKAG2 syndrome, Fabry disease, and cardiac amyloidosis. Their differential diagnosis is essential because these phenocopies present specific diagnostic and therapeutic strategies that can impact the natural evolution of disease. The present report reveals the case of a young patient in which this differential diagnosis was challenging, both due to difficulties in accessing specific exams and the overlapping of diseases that made his diagnosis hard, and describes the disease distribution in his family. This patient is part of a broader research project approved by the Research Ethics Committee of the Universidade do Estado do Amazonas under approval number 7.108.530 and CAAE 55200322.5.3009.516.

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