Holt-Oram syndrome is a disorder that affects bones in the arms and hands (the upper limbs) and may also cause heart problems. All people with this disorder have at least one limb abnormality that affects bones in the wrist (carpal bones). Often, these wrist bone abnormalities can be detected only by X-ray. Affected individuals may have additional bone abnormalities that 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, and abnormalities that affect the collar bone and shoulder blades. Bone abnormalities may affect each arm differently, and in these cases the left side is usually affected more than the right side. Sometimes, only one arm and/or hand (on either the right side or the left side) is affected.
Congenital heart disease is the most common birth defect and the leading cause of all infant deaths in the United States. Mutations in the gene TBX5 have been shown to cause both rare and more prevalent forms of congenital heart disease, yet the underlying mechanisms have remained unclear.
Gregg Duester, Ph.D., professor of developmental biology at Burnham Institute for Medical Research (Burnham), along with Xianling Zhao, Ph.D., and colleagues, have clarified the role that retinoic acid plays in limb development.