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Holt-Oram syndrome


Other Names for this Disease

  • Atrio digital syndrome
  • Atriodigital dysplasia
  • Cardiac-limb syndrome
  • Heart-hand syndrome
  • Heart-hand syndrome, type 1
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.

Overview

What is Holt-Oram syndrome?

What are the signs and symptoms of Holt-Oram syndrome?

What causes Holt-Oram syndrome?

How is Holt-Oram syndrome diagnosed?

How might Holt-Oram syndrome be treated?

What is Holt-Oram syndrome?

Holt-Oram syndrome is a genetic condition characterized by skeletal abnormalities of the hands and arms (upper limbs) and heart problems. Affected people have at least one bone abnormality in the wrist, many of which can be detected only by X-ray. Additional skeletal abnormalities may also be present. About 75% of affected people have heart problems, including congenital heart defects and/or cardiac conduction disease (an abnormality in the electrical system that coordinates contractions of the heart chambers). Holt-Oram syndrome is caused by mutations in the TBX5 gene and is inherited in an autosomal dominant manner. Most cases result from new mutations in the gene and occur in people with no family history of the condition.[1]
Last updated: 9/16/2014

What are the signs and symptoms of Holt-Oram syndrome?

People with Holt-Oram syndrome have abnormally developed bones in their upper limbs. At least one abnormality in the bones of the wrist (carpal bones) is present. Additional bone abnormalities may also be present, such as a missing thumb, a long thumb that looks like a finger, partial or complete absence of bones in the forearm, an underdeveloped bone of the upper arm, and abnormalities of the collar bone or shoulder blades.[1]

About 75% of affected people have heart problems, which can be life-threatening. The most common problems are an atrial septal defect (ASD) and a ventricular septal defect (VSD). Some people 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 uncoordinated contraction of the heart muscle (fibrillation).[1]

The features of Holt-Oram syndrome are similar to those of a condition called Duane-radial ray syndrome but these two disorders are caused by mutations in different genes.[1]
Last updated: 9/16/2014

What causes Holt-Oram syndrome?

Holt-Oram syndrome is caused by changes (mutations) in the TBX5 gene. This gene gives the body instructions for making a protein involved in the development of the heart and upper limbs before birth. In particular, this gene appears to be important for dividing the developing heart into four chambers, and in regulating the development of bones in the arms and hands. When the TBX5 gene doesn't function properly, the features of Holt-Oram syndrome result.[2]

In some cases the mutation occurs for the first time in an affected person, while in other cases the mutation is inherited from a parent. However, in both of these cases, there is nothing a parent or pregnant female can do to cause this mutation to be present in a child.
Last updated: 9/16/2014

How is Holt-Oram syndrome diagnosed?

The diagnosis of Holt-Oram syndrome can be established based on physical features and family history. It can be confirmed through genetic testing looking for mutations in the TBX5 gene. Hand x-rays are usually performed for upper-limb malformations. A family history of this condition and/or cogenital heart malformations is also used as a diagnostic tool as a congenital heart malformation is present in 75% of individuals with Holt-Oram syndrome. An echocardiogram and electrocardiogram can be used to determine the presence and severity of heart defects and/or cardiac conduction disease.[3][4]

Holt-Oram syndrome can be excluded in individuals with congenital malformations involving the following structures or organ systems: ulnar ray only, kidney, vertebra, head and face region, auditory system (hearing loss or ear malformations), lower limb, anus, or eye.[3]
Last updated: 7/19/2011

How might Holt-Oram syndrome be treated?

The treatment of Holt-Oram syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists such as pediatricians, surgeons, cardiologists, orthopedists, and/or other health care professionals.[4]

Depending upon the severity of any upper limb abnormalities, treatment may consist of corrective or reconstructive surgery, the use of artificial replacements for portions of the forearms and hands (limb prosthetics), and/or physical therapy to help individuals enhance their motor skills. In those with mild cardiac conduction abnormalities, treatment may not be required. In more severe cases, an artificial pacemaker may be used. An artificial pacemaker overrides the heart's impaired electrical conducting system by sending electrical impulses to the heart that keep the heartbeat at a regular rate. Heart abnormalities may also be treated with certain medications, surgery, and/or other techniques. In such cases, the surgical procedures performed will depend upon the location and severity of the abnormalities and their associated symptoms.[4]

Affected individuals with heart defects may also be at risk for bacterial infection and inflammation of the lining of the heart's chambers and valves (endocarditis). So antibiotics should be prescribed before any surgical procedure, including dental procedures such as tooth extractions. In addition, because some individuals with certain heart defects may be susceptible to repeated respiratory infections, physicians may closely monitor such individuals to take preventive steps and to institute antibiotic and/or other appropriate therapies should such infections occur.[4]

Early intervention is important to ensure that children with Holt-Oram syndrome reach their potential. Special services that may be beneficial to affected children may include physical therapy and/or other medical, social, and/or vocational services.[4]
Last updated: 7/19/2011

References
  1. Holt-Oram Syndrome. Genetics Home Reference. December 2009; http://ghr.nlm.nih.gov/condition/holt-oram-syndrome. Accessed 7/19/2011.
  2. Holt-Oram syndrome. Genetics Home Reference. June 2014; http://ghr.nlm.nih.gov/condition/holt-oram-syndrome. Accessed 9/16/2014.
  3. McDermott DA, Fong JC, Basson CT. Holt-Oram Syndrome. GeneReviews. January 2011; http://www.ncbi.nlm.nih.gov/books/NBK1111/. Accessed 7/19/2011.
  4. Holt Oram Syndrome. National Organization for Rare Disorders (NORD). 2005; http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/523/viewAbstract. Accessed 7/19/2011.


Other Names for this Disease
  • Atrio digital syndrome
  • Atriodigital dysplasia
  • Cardiac-limb syndrome
  • Heart-hand syndrome
  • Heart-hand syndrome, type 1
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.