Holt-Oram syndrome, also known as the heart-hand syndrome, is an autosomal dominant disorder that affects bones in the arms and hands (the upper limbs). It may also cause congenital heart defects. (Autosomal dominant means that the defective gene is located on an autosome, and only one copy of the gene, inherited from a parent who has the disorder, is sufficient to cause the disorder).
All people with this Holt-Oram syndrome have at least one limb abnormality that affects carpal bones) (wrist bones) which can be detected only by X-ray. Additional bone abnormalities can include:
- a missing thumb or a thumb that looks like a finger
- partial or complete absence of bones in the forearm
- an underdeveloped bone of the upper arm
- abnormalities that affect the collar bone and shoulder blades.
Holt-Oram syndrome is caused by mutations in the TBX5 gene cause which plays a role in the development of the heart and upper limbs before birth. In particular, the TBX5 gene appears to be important for the process that divides the developing heart into four chambers (cardiac septation). The TBX5 gene also appears to play a critical role in regulating the development of bones in the arm and hand. The mutations in this gene probably disrupt the development of the heart and upper limbs, leading to the characteristic features of Holt-Oram syndrome.
Holt-Oram syndrome is named for Mary Clayton Holt, an English cardiologist born in 1924 and Samuel Oram, an English cardiologist, 1913-1991.