Holt-Oram syndrome: A genetic syndrome characterized by the combination of heart disease and malformations of the upper limb. The heart defect is usually an atrial septal defect (ASD) and, less often, a ventricular septal defect (VSD), although other cardiovascular malformations have been reported. The upper limb malformations most often affect the forearm and thumb. The thumb may be absent or it may be a nonopposable fingerlike digit. All gradations in defects in the upper limb and shoulder girdle have been reported.
The Holt-Oram syndrome (HOS) is inherited in an autosomal dominant manner and is due to mutations in the TBX5 (T-box 5) gene located in chromosome region 12q24.1. The GATA4 (GATA-binding protein 4) gene is known to interact with TBX5.
The syndrome was first clearly delineated in 1960 by M. Holt and Samuel Oram as "Familial heart disease with skeletal malformations." Called also the heart-hand syndrome, cardiac-limb syndrome, and atriodigital dysplasia.
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