Holt-Oram syndrome, also called heart-hand syndrome, is an inherited disorder characterized by abnormalities of the upper limbs and heart. Holt and Oram first described this condition in 1960 in a 4-generation family with atrial septal defects (ASDs) and thumb abnormalities.

Holt-Oram syndrome is the prototype of heart-hand syndromes and has recently been mapped to the long arm of chromosome 12 (12q2). It must be differentiated from heart-hand syndrome type II (Tobatznik\'s syndrome) and heart-hand syndrome type III , which are phenotypically similar. The latter do not map to 12q2, and atrial septal defects do not occur in these conditions

Although the clinical manifestations are variable, upper limb abnormalities are always present. Abnormalities may be unilateral or bilateral and asymmetric and may involve the radial, carpal, and thenar bones. Aplasia, hypoplasia, fusion, or anomalous development of these bones produces a spectrum of phenotypes, including triphalangeal or absent thumbs. Occasionally, upper limb malformation can be sufficiently severe to produce phocomelia (a malformation in which the hands are attached close to the body); this has been termed pseudothalidomide syndrome. The most prevalent findings in persons with Holt-Oram syndrome are malformations or fusions of the carpal bones. Carpal bone abnormalities are the only findings present in every affected individual, although these anomalies may be evident only radiographically in some patients.

Approximately 75% of patients have some cardiac abnormality. In most patients, the abnormality is either an ASD or a ventricular septal defect (VSD), which varies in number, size, and location. ASDs are usually of the secundum variety, while VSDs tend to occur in the muscular trabeculated septum. Cardiac anomalies also may include cardiac conduction defects such as progressive atrioventricular block and atrial fibrillation. These anomalies are frequently present even in the absence of septal defects.