TBX5 and Holt-Oram syndrome: Haploinsufficiency of TBX5 is the cause of Holt–Oram syndrome (HOS), an autosomal dominant disorder associated with congenital heart defects (mostly septal defects, the atrial septal defect being the most frequent), conduction abnormalities, and limb anomalies (bilateral and asymmetric radial ray defects) [59].