Early-onset severe dilated cardiomyopathy in a child with COL5A1 and ABCC9 variants: a possible complex genetic contribution

Abstract We report a 16-month-old boy presenting with progressive respiratory distress and generalised oedema. Chest radiography revealed pulmonary oedema, and echocardiography demonstrated severe left ventricular dilation with markedly reduced systolic function (ejection fraction ∼ 30%). There was no clinical, laboratory, or cardiac magnetic resonance evidence supporting myocarditis. Cardiac MRI demonstrated a non-ischaemic dilated cardiomyopathy phenotype without evidence of myocardial fibrosis. Despite intensive medical therapy, only partial functional recovery was observed. Aetiological evaluation using clinical exome sequencing identified a heterozygous likely pathogenic ABCC9 variant together with a heterozygous COL5A1 variant of uncertain significance. Although the pathogenic contribution of the COL5A1 variant remains uncertain, its coexistence with the ABCC9 variant may have contributed to the unusually early and severe clinical presentation.