Holt-Oram syndrome is the name given to the association of heart defect and upper limb abnormality first described by Dr Mary Holt and Dr Samuel Oram in 1960. Since then over a hundred cases have been reported worldwide.

Heart defects
Most commonly this is an Atrial Septal Defect (ASD) or Ventricular Septal Defect (VSD) but other congenital heart defects can occur. Conduction disturbances are often seen on electrocardiography (ECG) and may be the only sign of the condition.

Upper limb
Abnormalities affect both arms but not necessarily in the same way. The thumb is usually abnormal (triphalangeal, like a finger), absent or underdeveloped. The forearms may be short or absent. The shoulders are usually narrow and sloping. The mildest abnormalities are abnormal bending of the fifth finger and limited rotation of the joints of the forearms which allow palm of hands to face up. The most severe involve absence of all or part of the upper limb.

The lower limbs are not involved and no other abnormalities are seen in the Holt-Oram syndrome.

Inheritance patterns
The Holt-Oram syndrome is inherited by autosomal dominant inheritance. Where a child is born to an affected parent there is a 50/50 chance of that child having the syndrome. Because the severity is very variable a mildly affected parent may have a severely affected child. The causative gene has been identified (TBX5) enabling molecular genetic diagnosis.

Prenatal diagnosis
In families where the specific gene mutation has been identified, genetic prenatal diagnosis may be available by Chorionic Villus Sampling.

Medical text written May 1995 by Dr R Newbury-Ecob. Last updated December 2005 by Dr R Newbury-Ecob, Consultant in Clinical Genetics, Clinical Genetics Service, St Michael's Hospital, Bristol, UK.

Further Online Resources
Medical texts in The Contact a Family Directory are designed to give a short, clear description of specific conditions and rare disorders. More extensive information on this condition can be found on a range of reliable, validated web sites and links to them are included in the CD-ROM version of this Directory. Further information on these resources can be found in our Medical Information on the Internet article.

There is currently no effective support group covering Holt-Oram syndrome. This medical description is retained for information purposes. Families can use Contact a Family's Freephone Helpline for advice, information and, where possible, links to other families. Support specifically for the upper limb abnormalities of Holt-Oram Syndrome is available from Reach (see entry, Upper Limb Abnormalities.) Contact a Family's web-based linking service Making Contact.org can be accessed at http://www.makingcontact.org