A heterozygous missense variant in the RBM20 gene was identified in a 23-year-old male, leading to heart failure and the need for an implantable cardioverter-defibrillator due to arrhythmic risk.
This case highlights the critical role of genetic testing in young patients with nonischaemic cardiomyopathy to identify high-risk variants like RBM20, enabling family screening and personalized arrhythmic risk stratification.
ABSTRACT The RBM20 gene, located on chromosome 10q25.2, encodes a serine/arginine‐rich protein essential for post‐transcriptional splicing of several cardiac genes, including titin. Pathogenic variants in RBM20 are increasingly recognized as causes of familial dilated cardiomyopathy (DCM) with a high risk of heart failure and sudden cardiac death. We describe a 23‐year‐old man who presented with heart failure with mildly reduced ejection fraction secondary to DCM caused by a heterozygous missense variant in the RBM20 gene (c.1907G>A; p.Arg636His). Comprehensive clinical evaluation excluded non‐genetic aetiologies, and family screening confirmed the same variant in his asymptomatic mother and in his sister who had DCM. The patient received guideline‐directed medical therapy and was referred for implantable cardioverter‐defibrillator placement due to elevated arrhythmic risk associated with the RBM20 variant. This case highlights the importance of genetic testing in young patients with nonischaemic cardiomyopathy, early identification of at‐risk relatives, and personalized management guided by current European Society of Cardiology recommendations. Furthermore, emerging research on antisense oligonucleotide therapy and gene editing provides promising avenues for future treatment of RBM20 cardiomyopathy.
Bueno et al. (2026) studied this question. A heterozygous missense variant in the RBM20 gene was identified in a 23-year-old male, leading to heart failure and the need for an implantable cardioverter-defibrillator due to arrhythmic risk.