Holt-Oram Syndrome

What is Holt-Oram syndrome?

Holt-Oram syndrome is a rare, congenital (present at birth) disorder. It often involves abnormal bones in your hands, wrists and arms, as well as heart problems.

The skeletal abnormalities can affect one or more body parts on one side or both. Heart problems may be structural defects or abnormal electrical impulses that affect your heart rate and rhythm.

Holt-Oram syndrome may also be called:

• Atrio-digital dysplasia.
• Atrio-digital syndrome.
• Cardiac-limb syndrome.
• Heart-hand syndrome, type 1.
• HOS or HOS1.
• Ventriculo-radial syndrome.

What are the symptoms of Holt-Oram syndrome?

Signs and symptoms of Holt-Oram syndrome vary from person to person. Sometimes, providers can only see them with medical imaging, such as X-ray, CT scan (computed tomography scan) or MRI (magnetic resonance imaging).

If you have Holt-Oram syndrome, at least one of your wrist bones didn’t develop properly. Other bone irregularities may include:

• Abnormalities in your collarbone or shoulder blades.
• A hand that looks to be split.
• Inability to fully extend or rotate an affected arm.
• Kyphosis (hunched back) or scoliosis (when your spine curves sideways).
• A missing thumb, or a long thumb that looks more like a finger.
• Partial bones or no bones in your forearm.
• Underdeveloped bone in your upper arm.

Most people with Holt-Oram syndrome also have cardiac abnormalities. The most common is a hole in the wall that separates the left and right sides of your heart. This wall is called your septum. There are two types of septal defects:

• An atrial septal defect is a hole between your heart’s two upper chambers (your atria).
• A ventricular septal defect is a hole between your heart’s two lower chambers (your ventricles).

Some people with the syndrome may have cardiac conduction disease. That affects the electrical impulses that control your heart’s contractions. Cardiac conduction disease can cause bradycardia (an abnormally slow heartbeat) or atrial fibrillation (rapid, uncoordinated contractions). This may be present at birth, but can also develop over time. Your healthcare team will need to monitor this throughout your life.

Heart problems associated with Holt-Oram syndrome may cause symptoms like:

• Failure to thrive (grow).
• Fatigue (extreme tiredness).
• High blood pressure in your lungs (pulmonary hypertension).
• Shortness of breath.
• Trouble breathing.

What causes Holt-Oram syndrome?

Holt-Oram syndrome is most often caused by a change (mutation) in the TBX5 gene. This gene makes a protein that contributes to upper limb development as a fetus grows. The protein is also vital as the heart divides into four chambers.

The TBX5 mutation can be inherited. But most cases involve a new mutation when there’s no family history of the disorder.

Sometimes, people with Holt-Oram syndrome don’t have the TBX5 genetic mutation. Scientists don’t yet understand what causes the disorder in those individuals, though it may be mutations in proteins that interact with TBX5.

How is Holt-Oram syndrome diagnosed?

A healthcare provider may suspect Holt-Oram syndrome based on a physical exam and a discussion of family history. They may order certain tests, including:

• Medical imaging, like X-rays of your hands, wrists and arms.
• Echocardiogram (echo), which produces images of your heart to detect any problems with its structure or pumping action.
• Electrocardiogram (ECG or EKG), which measures the electrical activity of your heart.
• Genetic testing to confirm a mutation, which usually involves a blood test.

Some people with Holt-Oram syndrome are diagnosed when they’re babies. But others aren’t diagnosed until later in life. This can happen when a person develops heart symptoms or discovers a bone abnormality by accident during other medical testing.

How is Holt-Oram syndrome treated?

There’s no cure for Holt-Oram syndrome. Treatment depends on what symptoms you have and how severe they are.

Some people have mild cases and don’t require treatment. Others need extensive medical attention. The goals of treatment are for people to be able to use their hands and arms as much as possible and to prevent heart complications.

Treatments may include:

• Antiarrhythmic medications to control heart rate and rhythm.
• Implanting a medical device like a pacemaker to control heart rate and rhythm.
• Surgery to correct a hole in your heart.
• Braces or surgeries to correct bone abnormalities.
• Prosthetics (artificial replacements for parts of your hand or arm).

People with this condition may need a team of specialists, including:

• Cardiologists and cardiac surgeons, who specialize in heart conditions.
• Orthopedic surgeons, who specialize in bones.
• Pediatricians.
• Occupational therapists, who can help improve performance with daily activities, like eating and writing.
• Physical therapists, who can help strengthen abnormal body parts.

Can Holt-Oram syndrome be prevented?

Because a genetic mutation usually causes Holt-Oram syndrome, you can’t prevent it. If you have the disorder and get pregnant, there’s a 50% chance of passing on the mutated gene to your baby. Prenatal genetic testing can check for the gene mutation. Your healthcare provider may also recommend genetic counseling for close family members

What is the outlook for people with Holt-Oram syndrome?

The prognosis (outlook) for people with Holt-Oram syndrome varies widely. Some people have only minor irregularities in their wrists and no physical limitations. Others have significant bone problems.

However, 75% have a congenital structural defect in their hearts. Some people don’t experience any symptoms and only need regular follow-up with a cardiologist for monitoring. But some heart defects can be life-threatening and require surgery.

How can my family learn to cope with Holt-Oram syndrome?

Visible differences can make children feel self-conscious and affect their social interactions. To help:

• Consider meeting with a mental health professional to help your child understand their emotions.
• Discuss the condition openly with your child, using simple language.
• Teach the people your child interacts with frequently about the condition.
• Join a support group or national advocacy organization, where you can meet other families who understand.
• Make sure teachers provide a supportive plan for your child to learn and socialize, free from bullying.
• Practice how to respond to people who ask about it. For example, “I was born with a bone in my wrist that’s not like everyone else’s.”

A note from Cleveland Clinic

Holt-Oram syndrome is a condition often involving abnormal bones in your hands, wrists and arms, as well as heart problems. If your child has the syndrome, healthcare providers can offer ways to improve the use of their arms and hands. They can also help screen other family members and prevent complications from heart defects.