Case report: Severe arrhythmogenic cardiomyopathy in a young girl with compound heterozygous DSG2 and MYBPC3 variants with a 6-year follow-up

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  FIGURE 1. Objective findings at the initial examination of the 6-year-old patient with arrhythmogenic cardiomyopathy (ACM) and dilated cardiomyopathy (DCM). (A) Timeline of clinical investigations and disease-related events. (B) Chest radiograph revealing the protrusion of the right second and left fourth arches. (C) Electrocardiogram showing epsilon waves and T-wave inversion in leads V1-6 and lead III. The light blue arrowheads in leads V1-2 indicate epsilon waves. (D) Two-dimensional (2D) echocardiographic image acquired in the parasternal long-axis view at end-diastole. Echocardiography confirmed reduced contraction, mainly in the right ventricular outflow tract (RVOT), which measured 2.44 cm. RV, right ventricle; LV, left ventricle. (E) Representative 2D echocardiographic images acquired in the apical four-chamber view at end-diastole (left) and end-systole (right), which were used to calculate the RV fractional area change, were found to be 18.0%. (F) Cardiac magnetic resonance imaging (MRI) demonstrated dyskinesis of the RV base (green arrow), with an RV end-diastolic volume index (RVEDVI) of 139.9 mL/m2, RV ejection fraction (RVEF) of 9.7%, and a LV ejection fraction (LVEF) of…

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  FIGURE 2. Trio analysis for genetic variants and pedigree analysis. (A) Direct Sanger sequencing confirmed the inheritance of variants in desmoglein-2 (DSG2), desmocollin-2 (DSC2), and myosin-binding protein C (MYBPC3) genes in the proband and her parents. (B) Family pedigree analysis of the 6-year-old proband (III-1) demonstrating compound heterozygosity for DSG2 p. Arg119* and DSG2 p. Arg292Cys variants, with an additional heterozygous MYBPC3 p. Arg820Gln variant. The proband inherited the DSG2 p. Arg119* and MYBPC3 p. Arg820Gln variants paternally (II-2), while the DSG2 p. Arg292Cys variant was transmitted maternally (II-2). The DSC2 p. Arg375Gln variant, whose pathogenic significance remains unclear, was inherited from the mother. The proband’s paternal grandmother (I-4) was diagnosed with dilated cardiomyopathy (DCM) at the age of 48 and succumbed to a cardiogenic cerebral infarction at the age of 62. The arrow indicates the index patient. Solid black symbols in the pedigree denote individuals with a history of cardiac disease. CRC, colorectal cancer.

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  FIGURE 3. Clinical findings from the most recent pre- or post-admission examinations at 10.5 years of age (4 years after diagnosis) when the patient developed heart failure. (A) Cardiac magnetic resonance imaging (MRI) performed 17 days before admission showed marked increases in ventricular volume and decreased contractility not only in the right ventricle (RV) but also in the left ventricle (LV), with a RV ejection fraction (RVEF) of 9.7% and a LV ejection fraction (LVEF) of 9.5%. Septal displacement (diastole, green arrow) and aneurysmal thinning and dyskinesis of the anterolateral wall of the LV (systole, green arrow) were observed. (B) Chest radiograph at admission shows marked cardiomegaly, and echocardiography reveals bilateral ventricular dilatation and severe hypokinesis. (C) Left ventricular apical thrombus (17 × 11 mm) confirmed 3 weeks after admission.