Costello Syndrome

What Is Costello Syndrome?

Costello syndrome is a very rare genetic condition. It happens when there's a change (mutation) in a gene called the HRAS gene. This happens in a child's DNA before birth.

Costello causes problems that affect the heart, muscles, bones, skin, brain, and spinal cord. There's no cure for the condition, but doctors can help kids manage most symptoms.

What Are the Signs & Symptoms of Costello Syndrome?

Parents of a baby with Costello syndrome (SIN-drome) usually notice that the baby is having trouble feeding. The baby often has several of these features, which are noticed at birth or soon after:

• a large head
• thick lips
• wide nostrils
• slow weight gain (failure to thrive)
• loose skin on the neck, fingers, palms of the hands, and soles of the feet
• very flexible joints
• wrists angled toward the pinky side

As the child grows, other signs usually appear, such as:

• smiling, walking, talking, and doing other things later than most children
• skin tags or warts on the face and around the anus
• tightly curled or very fine hair
• tight heel (Achilles) tendons that cause toe walking (walking with heels off the floor)
• heart rhythm problems
• dry, hard skin on the hands and feet
• a sideways bend in the backbone (scoliosis)
• a sharp forward bend in the backbone (kyphosis)
• slow growth
• short height

Other changes caused by Costello syndrome can be seen only on blood tests or imaging tests. These include:

• low levels of growth hormone
• high insulin levels, leading to low blood sugar levels
• thickened heart muscle and other heart problems
• brain and spinal cord changes

Children who have Costello syndrome also have a higher risk for some types of tumors, which can be benign (not cancer) or malignant (cancer).

What Causes Costello Syndrome?

Costello syndrome happens because of a change (mutation) in a gene called the HRAS gene. The mutation makes cells grow and divide more than they should. Everyone has two copies of the HRAS gene. It only takes one changed gene to cause Costello syndrome.

The HRAS gene helps make a protein called HRas. Different changes in the HRAS gene affect the HRas protein in different ways. That means that two children with Costello syndrome may have different symptoms, and the symptoms can affect one child more than the other.

A child will have Costello syndrome if he or she:

• inherits a change in the HRAS gene from either the mother or father
• has a new mutation in the HRAS gene

Most children with Costello syndrome have a new mutation. This means that neither parent has a change in an HRAS gene. The change is a random accident, so there is nothing the parents could have done to prevent it.

Costello syndrome is a RASopathy. RASopathies are genetic conditions that cause similar symptoms because they're caused by a change in one of the Ras family of proteins, which includes HRas, or in other genes that closely interact with the Ras proteins.

How Is Costello Syndrome Diagnosed?

To find out if a child has Costello syndrome, doctors will:

• ask about the child's symptoms and
• do an exam
• order genetic testing to look for a mutation in the HRAS gene in the child's DNA
• send the child to see specialists, who might order these imaging tests:
  • magnetic resonance imaging (MRI)
  • ultrasound scan
  • echocardiogram

How Is Costello Syndrome Treated?

There is no cure for Costello syndrome. But medical care can help almost every symptom.

For example:

• A child can get liquid food through a tube in the nose that goes down the throat to the stomach (a nasogastric or NG tube) or one that goes through the belly wall into the stomach (a G-tube).
• Medicines and surgery can help heart problems.
• Occupational therapy and physical therapy can help improve hand strength and use of the fingers.
• Surgery to lengthen short heel (Achilles) tendons can help a child walk, run, and play better.
• Dermatologists can freeze off skin tags with dry ice or a freezing spray.

A team of medical specialists cares for children with Costello syndrome. The team may include:

• a pediatrician: for routine care
• a cardiologist and cardiothoracic surgeon: for heart problems
• an orthopedic surgeon: for the treatment of bone, muscle, and tendon problems
• a neurosurgeon: for treatment of brain and spinal cord problems
• a dermatologist: for skin problems
• an endocrinologist: for hormone problems
• a speech therapist: for speech problems
• a dietitian: for help with nutrition
• a social worker: for help with social services

Meeting with a genetic counselor can help families learn what to expect and understand how Costello syndrome can run in families.

What Else Should I Know?

Children with Costello syndrome tend to be friendly and outgoing, but most learn more slowly than other children of the same age. They'll need regular checkups so doctors can look for:

• changes in the heart muscle
• changes in the heart's rhythm
• muscle, nerve, and bladder cancer

The medical challenges of Costello syndrome can be stressful for any family. But you're not alone. The care team will work together to help manage problems, and to support your family. Ask them how to find local groups that can help your child feel connected and offer resources for the family.

You also can find information and support online at:

• The Costello Syndrome Family Network
• International Costello Syndrome Support Group
• NORD (National Organization for Rare Disorders)