The clinical and genetic spectrum of the Holt-Oram syndrome (heart-hand syndrome)

Holt-Oram syndrome may be caused by mutations in a gene on chromosome 12q2. Holt-Oram syndrome is an inherited disorder characterized by skeletal deformities and heart defects. Researchers performed clinical and genetic-linkage studies on two large, unrelated families with the syndrome. In Family A, 26 of 49 members were affected and 18 surviving members were evaluated. All affected members of Family A had skeletal abnormalities and cardiovascular disease. Eleven had heart conduction diseases. In Family B, 18 of 31 affected members were still alive for examination. All affected family members had skeletal abnormalities and had severe skeletal deformities more frequently than affected members of Family A. In contrast, Family B had less severe and less frequent cardiovascular disease than Family A and only one member had a heart conduction disease. Genetic analysis revealed a linkage of the syndrome to mutations on chromosome 12.