Alternative Names
Atriodigital dysplasia; Atrio-digital syndrome; Cardiac-limb syndrome; Heart-hand syndrome, type ; HOS; Ventriculo-radial syndrome
Symptoms & Characteristics
Holt-Oram syndrome is a genetic condition that affects bones in the arms and hands and often has associated heart problems.
Bone abnormalities may affect each arm differently. Sometimes, only one arm and/or one hand is affected. Bone abnormalities may include:
- Wrist bone (carpal bone) abnormalities are always present but sometimes, can only be detected by X-ray.
- Thumbs can be absent, partial or look like a finger.
- Forearm bones can be absent or partial.
- Upper arm bones may be underdeveloped.
- Collar bones and shoulder blades may have abnormalities.
Heart defects are present in 75% of affected people. Heart defects may include:
- Atrial septal defects (ASD) , which are caused by a hole in the wall between the left and right upper chambers of the heart (called atria).
- Ventricular septal defects (VSD), which are caused by a hole in the wall between the left and right lower chambers of the heart (called ventricles).
- Cardiac conduction disease, which is caused by abnormalities in the electrical system that coordinates contractions of the heart chambers. Cardiac conduction disease can occur alone or along with other heart defects.
The characteristics vary greatly, even among affected members of the same family.
Treatment
There is no cure for Holt-Oram syndrome. However, early diagnosis and treatment can help to manage some of the symptoms and sometimes prevent related problems.
How Common Is It?
About 1 in 100,000 people worldwide are affected with Holt-Oram syndrome.
Genetics & Inheritance
Greater than 70% percent of people with Holt-Oram have mutations in a gene called TBX5 on chromosome 12 at the location p24.1. The cause(s) of Holt-Oram syndrome in the remaining 30% of affected people is unknown.
We all have two copies of the TBX5 gene - one from each parent. In Holt-Oram syndrome, having a mutation in a single gene copy is sufficient to cause the disease. This is called autosomal dominant inheritance.
- About 85% of affected people are the first one in their family to be affected. Their mutation is a result of a sporadic, new ("de novo") mutation.
- An affected person has a 50% chance with each pregnancy to have an affected child.
Parents of an affected person may want to consider genetic evaluations for Holt-Oram syndrome themselves. If a gene mutation has been identified in an affected person, genetic testing may also be considered. The benefits and limitations of such evaluations and testing should be discussed with a qualified health care professional.
- If both parents have negative genetic testing and normal genetic evaluations, recurrence risk to have another affected child is believed to be very low.
There are other genetic conditions that have features that overlap with Holt-Oram syndrome. Some of these conditions include thrombocytopenia-absent radius (TAR) syndrome, fanconi anemia, Duane-radial ray syndrome, and Heart-Hand syndromes I and III. A genetic consultation with a trained genetic professional is important for a complete evaluation, accurate diagnosis, as well as discussion of the benefits and limitations of testing and recurrence risk.
Genetic Testing
Clinical genetic testing for Holt-Oram syndrome may be available through an in person genetic consultation for people who are considered at risk. Use our find a genetic professional directory to locate a trained genetic professional in your area.
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