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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
More Names
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Your Question

During a recent meeting with a geneticist regarding my youngest son, my two boys and I were diagnosed with Holt-Oram syndrome. Why is my youngest son affected much worse than myself and my oldest son? Why, after 24 years, was I just diagnosed? I have been to doctors all my life. Also, what can I do to get the help needed to improve the well being of my boys and myself?

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

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 individuals have at least one bone abnormality in the wrist, and they may have additional skeletal abnormalities. About 75 percent of individuals with Holt-Oram syndrome have heart problems, including congenital heart defects and/or cardiac conduction disease, which is an abnormality in the electrical system that coordinates contractions of the heart chambers. Holt-Oram syndrome is caused by mutations in the TBX5 gene. Most cases result from new mutations in this gene and occur in people with no history of the disorder in their family.[1]
Last updated: 7/19/2011

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 in affected individuals. Additional bone abnormalities may also be present, including 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. These skeletal abnormalities may affect one or both of the upper limbs. If both upper limbs are affected, the bone abnormalities can be the same or different on each side. In cases where the skeletal abnormalities are not the same on both sides of the body, the left side is usually more severely affected than the right side.[1]

About 75 percent of individuals with Holt-Oram syndrome have heart (cardiac) problems, which can be life-threatening. The most common problems are a hole in the muscular wall (septum) that separates the upper right and left sides of the heart (atria), called an atrial septal defect (ASD) and a hole in the septum between the lower chambers of the heart (ventricles), called a ventricular septal defect (VSD). Some affected individuals 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). Cardiac conduction disease can occur along with other heart defects (such as ASD or VSD) or as the only heart problem.[1]

The features of Holt-Oram syndrome are similar to those of a condition called Duane-radial ray syndrome; however, these two disorders are caused by mutations in different genes. To read more about this condition, click on the link above.[1]
Last updated: 7/19/2011

Can signs and symptoms of Holt-Oram syndrome be different among family members?

Yes, signs and symptoms can vary from person to person, even among members within the same family. The upper-limb malformations can vary, even within affected families, and may one or both sides of the body. The features of this condition varies by individual and largely depends on the severity of the congenital heart malformation. Potential complications, which can be life threatening if not recognized and appropriately managed, include: congestive heart failure, pulmonary hypertension, arrhythmias, heart block, atrial fibrillation, and infectious endocarditis.[2]
Last updated: 7/19/2011

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.[2][3]

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.[2]
Last updated: 7/19/2011

Can a diagnosis of Holt-Oram syndrome be missed?

Yes. While all individuals have an upper-limb defect, the broad range of severity of these findings is such that some individuals with the mildest upper-limb malformations and no or mild congenital heart malformation may escape diagnosis. These individuals may only be diagnosed when a more severely affected relative is born or when symptoms develop in middle age as a result of cardiac abnormalities.[2]
Last updated: 7/19/2011

How can I find a genetics professional in my area?

Genetics clinics are a source of information for individuals and families regarding genetic conditions, treatment, inheritance, and genetic risks to other family members. More information about genetic consultations is available from Genetics Home Reference. To find a genetics clinic, we recommend that you contact your primary healthcare provider for a referral.

The following online resources can help you find a genetics professional in your community:
Last updated: 10/18/2013

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.[3]

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.[3]

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.[3]

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.[3]
Last updated: 7/19/2011