Reviewed June 2006
What is Holt-Oram syndrome?
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.
About 75 percent of individuals with Holt-Oram syndrome have heart problems. The most common problem is a defect in the muscular wall, or septum, that separates the right and left sides of the heart. Atrial septal defects (ASD) are caused by a hole in the septum between the left and right upper chambers of the heart (atria), and ventricular septal defects (VSD) are caused by a hole in the septum between the left and right lower chambers of the heart (ventricles). Sometimes people with Holt-Oram syndrome have cardiac conduction disease, which is caused by abnormalities in the electrical system that coordinates contractions of the heart chambers. Cardiac conduction disease can lead to problems such as a slower-than-normal heart rate (bradycardia) or a rapid and ineffective contraction of the heart muscles (fibrillation). Cardiac conduction disease can occur along with other heart defects (such as septal defects) or as the only heart problem in people with Holt-Oram syndrome.
How common is Holt-Oram syndrome?
Holt-Oram syndrome is estimated to affect 1 in 100,000 individuals.
What genes are related to Holt-Oram syndrome?
Mutations in the TBX5 gene cause Holt-Oram syndrome.
The TBX5 gene plays a role in the development of the heart and upper limbs before birth. In particular, this 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. Mutations in this gene probably disrupt the development of the heart and upper limbs, leading to the characteristic features of Holt-Oram syndrome.
Read more about the TBX5 gene.
How do people inherit Holt-Oram syndrome?
Holt-Oram syndrome is considered an autosomal dominant disorder, which means one copy of the altered gene in each cell is sufficient to cause this syndrome. Many cases of Holt-Oram syndrome result from new mutations in the TBX5 gene and occur in people with no history of the disorder in their family.
Where can I find information about treatment for Holt-Oram syndrome?
These resources address the management of Holt-Oram syndrome and may include treatment providers.
You might also find information on treatment of Holt-Oram syndrome in
Educational resources and Patient support.
Where can I find additional information about Holt-Oram syndrome?
You may find the following resources about Holt-Oram syndrome helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
What other names do people use for Holt-Oram syndrome?
- Atriodigital dysplasia
- Atrio-digital syndrome
- Cardiac-limb syndrome
- Heart-hand syndrome, type 1
- Ventriculo-radial syndrome
What if I still have specific questions about Holt-Oram syndrome?
Where can I find general information about genetic conditions?
The Handbook provides basic information about genetics in clear language.
These links provide additional genetics resources that may be useful.
What glossary definitions help with understanding Holt-Oram syndrome?
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? in the Handbook.