Comprehensive genetic testing in a 46-year-old man with syndromic dilated cardiomyopathy identified likely pathogenic frameshift variants in the CD36 and TNXB genes.
Case Report (n=1)
This case highlights the potential oligogenic mechanisms involving CD36 and TNXB variants in patients with syndromic dilated cardiomyopathy, emphasizing the value of comprehensive genetic testing.
Abstract Background Dilated cardiomyopathy (DCM) is a major cause of heart failure and sudden cardiac death and has traditionally been regarded as a predominantly monogenic disorder. However, advances in next-generation sequencing have revealed a more complex genetic architecture with increasing recognition of oligogenic and polygenic contributions; particularly in patients presenting with extracardiac manifestations. In such cases careful phenotypic characterization and integrative interpretation of genetic findings are essential for accurate diagnosis and management. Case Summary We report the case of a 46-year-old man who presented with progressive exertional dyspnea (New York Heart Association class II–III). His medical history was notable for childhood-onset epilepsy, visual impairment, musculoskeletal abnormalities and infertility. Transthoracic echocardiography demonstrated severe left ventricular dilatation with reduced ejection fraction (20%).Cardiac magnetic resonance imaging confirmed severe biventricular systolic dysfunction and revealed mid-to-basal myocardial fibrosis on late gadolinium enhancement imaging. Given the prominent multisystem involvement and exclusion of secondary causes a syndromic cardiomyopathy was suspected. Comprehensive genetic testing identified likely pathogenic frameshift variants in the CD36 and TNXB genes, while additional variants of uncertain significance were detected in MT-TK and STXBP1. These findings suggested a potential oligogenic contribution involving pathways related to myocardial energy metabolism and extracellular matrix integrity. Guideline-directed medical therapy for heart failure with reduced ejection fraction was initiated, and the patient was enrolled in multidisciplinary follow-up with genetic counseling for first-degree relatives. Discussion This case highlights the limitations of a strictly monogenic framework in dilated cardiomyopathy and underscores the importance of considering oligogenic mechanisms in patients with syndromic features. Integrative evaluation combining detailed phenotyping, advanced cardiac imaging and genetic analysis may provide valuable insights into complex cardiomyopathy phenotypes and support personalized clinical management.
Aydın et al. (Wed,) conducted a case report in Syndromic Dilated Cardiomyopathy (n=1). CD36 and TNXB variants was evaluated. Comprehensive genetic testing in a 46-year-old man with syndromic dilated cardiomyopathy identified likely pathogenic frameshift variants in the CD36 and TNXB genes.