Costello Syndrome

What is Costello syndrome?

Costello syndrome is a rare genetic condition that affects multiple organs including the brain, bones, heart, stomach, muscles, kidneys and skin. A genetic change causes proteins to tell cells to grow and divide more often than they need to. Because cells are multiplying too quickly in Costello syndrome, you’re more at risk of developing cancerous or noncancerous tumors.

How common is Costello syndrome?

Costello syndrome is a rare condition that affects at least 100 to 1,500 people worldwide.

What are the symptoms of Costello syndrome?

Costello syndrome symptoms range in severity. Symptoms affect different parts of your body including your brain, bones, heart, muscles and skin. Symptoms may include:

• Heart problems (arrhythmia, hypertrophic cardiomyopathy).
• Feeding difficulties during infancy that sometimes require a feeding tube.
• Curve of the spine (scoliosis or kyphosis).
• Intellectual disability (mild to moderate) and growth abnormalities of the brain (Chiari malformation).
• Vision and dental problems.
• Structural kidney differences.
• Weak muscle tone (hypotonia).

Physical characteristics

People diagnosed with Costello syndrome have distinct physical characteristics like:

• Flexible finger and wrist joints.
• Tight cords on the back of your heel (Achilles tendon).
• Large head, mouth and full lips with wide nostrils and coarse facial features.
• Loose folds of skin on your hands and feet (cutis laxa).
• Slow growth during childhood and short stature during adulthood.
• Areas of skin that are darker than surrounding skin (hyperpigmentation).

Tumors

The genetic change responsible for a Costello syndrome diagnosis causes cells to continuously grow and divide. This causes tumors to form. Tumors can be cancerous or noncancerous (benign). Some of the most common types of tumors include:

• Papilloma (noncancerous): Small growths that look like warts form around your nose, mouth or anus.
• Rhabdomyosarcoma (cancerous): A childhood cancer that forms in muscle tissue.
• Neuroblastoma (cancerous): A tumor common in children and adolescents that forms in nerve cells.
• Transitional cell carcinoma (cancerous): A type of bladder cancer that forms in adults.

What causes Costello syndrome?

A genetic change (mutation) of the HRAS gene causes Costello syndrome. The HRAS gene creates the H-Ras protein that’s responsible for cell growth and cell division. When the HRAS gene has a mutation, the protein’s power switch can’t turn off. This causes the protein to overwork by creating too many proteins that tell cells that they need to grow and divide more frequently than they should.

Can you inherit Costello syndrome?

While you can inherit Costello syndrome from a parent, almost all cases of Costello syndrome are the result of a new genetic change that happens among people without any history of the condition in their biological family.

In rare cases of inheritance, Costello syndrome is autosomal dominantly inherited. This means that only one biological parent needs to have the gene change to pass it on to their child who’d have a 50% chance of inheriting it.

Who does Costello syndrome affect?

Costello syndrome could affect anyone. Although you can inherit the condition, most cases happen randomly or sporadically, without any history of the condition in someone’s family history (de novo).

How is Costello syndrome diagnosed?

A Costello syndrome diagnosis occurs in early childhood. Your healthcare provider will diagnose Costello syndrome after a physical examination of your child’s symptoms, followed by a genetic test to confirm the gene change responsible. Your provider will also ask if you have a history of any genetic conditions in your family since your child could inherit Costello syndrome.

Your provider’s diagnostic approach eliminates conditions that share the same symptoms. Physical symptoms of Costello syndrome are very similar to symptoms of both cardiofaciocutaneous syndrome (CFC syndrome) and Noonan syndrome. A genetic test to identify the gene responsible for symptoms sets each condition apart and leads to a complete diagnosis.

How is Costello syndrome treated?

Treatment for Costello syndrome addresses symptoms of the condition since there’s no cure. Treatment could include:

• Surgery to treat heart problems, feeding problems, curved spine, etc.
• Taking medications to treat heart symptoms (beta-blockers, calcium channel blockers, antiarrhythmic medications).
• Wearing corrective lenses or undergoing eye surgery to improve vision.
• Wearing a brace or participating in physical and occupational therapy to improve muscle strength and bone growth abnormalities.
• Enrolling in special education programs in school.
• Surgery or chemotherapy to address cancerous tumors or freezing off (with dry ice) noncancerous tumors.

How can I prevent Costello syndrome?

It’s difficult to prevent Costello syndrome because the condition occurs randomly and is unpredictable. If you know genetic conditions like Costello syndrome run in your biological family, talk to your provider about genetic testing to understand your risk.

What can I expect if I have Costello syndrome?

Costello syndrome is a lifelong condition without a cure. People diagnosed with Costello syndrome have a varied life expectancy that’s dependent on the severity of their symptoms, especially symptoms that affect the heart. Treatment addresses symptoms as well as tumors that form as a result of your body’s cells dividing too frequently. The outlook is positive with early treatment.

When should I see my healthcare provider?

Visit your healthcare provider if your child diagnosed with Costello syndrome experiences symptoms that affect their ability to thrive, especially if they have problems eating.

Visit the emergency room immediately if your child experiences symptoms that affect their heart, including:

• An abnormally slow or fast heartbeat.
• Shortness of breath.
• Chest pain.
• Fainting or feeling dizzy.

What questions should I ask my doctor?

You may want to ask your healthcare provider:

• Are there side effects to the treatment?
• Does my child need surgery?
• How often does my child need preventive checkups to monitor their symptoms?
• Does my child need to see a specialist?

A note from Cleveland Clinic

It may be overwhelming to hear that your child has a rare genetic condition, but your healthcare provider will offer the best care possible to treat your child’s symptoms. This will help them lead a healthy life. It’s important to monitor your child for symptoms, especially small tumors that form on their body as a result of their cells overworking. Early treatment leads to the best outlook.