Holt-Oram syndrome (HOS), also referred to as Heart–Hand syndrome, has an autosomal dominant pattern of inheritance with complete penetrance and varying degrees of expressivity. Pathogenic variants in the T-box transcription factor 5 (TBX5) gene have been reported in more than 85% of patients with HOS (Krauser et al. 2024). Bilateral malformations of upper limbs, congenital heart defects, and disturbances of the heart rhythm are the hallmark characteristics of HOS (Fig. 1) (Vanlerberghe et al. 2019). In 1960, Holt and Oram described nine individuals across four generations of a pedigree affected by atrial septal defects and congenital thumb malformations (Holt and Oram 1960). Ever since then, numerous studies have reported families with variable expressions of skeletal and cardiac manifestations of HOS.