Health Library

Costello Syndrome

Common Issues with Costello Syndrome

Heart Issues

The most common heart defect seen in those with Costello syndrome is hypertrophic cardiomyopathy. This is a thickening of the heart that causes the heart muscle to not work as well. Other types of heart concerns include:

• Pulmonic stenosis
• Arrhythmias
• Aortic dilatation

Muscle and Skeletal Abnormalities

Many people with Costello syndrome have differences in their muscles and bones. These can include:

• Decreased muscle tone (hypotonia)
• Loose or flexible joints
• Tight Achilles tendons
• Abnormal curvature of the spine (kyphoscoliosis)
• Short stature / height
• An abnormality in their wrists and fingers (ulnar deviation)
• Differences in the shape of their chest (pectus carinatum or excavatum)
• Developmental hip dysplasia
• Low bone density (osteoporosis or osteopenia)

Physical Features

People with Costello Syndrome have distinct facial features such as full lips and low-set ears, which can change over time. They may also have a large head (macrocephaly). Though those with Costello syndrome share many facial features, they also look like their own family members. They often have fine, curly hair, soft skin, and a deep, hoarse or whispery voice.

Learning and Development

Delay in reaching early developmental milestones is common for those with Costello syndrome. Infants often have trouble feeding due to low muscle tone (hypotonia). They may grow more slowly. Most people with Costello syndrome will have some intellectual disabilities, ranging from mild to moderate.

Other Issues

Neurologic
People who have Costello syndrome may have a structural abnormality of the brain called a Chiari I malformation, which can develop over time. They may also have a buildup of fluid on the brain (hydrocephalus). Some individuals have seizures.

Tumor Risks
Those with Costello syndrome have an increased risk of developing tumors. These include malignant tumors in their heart (rhabdomyosarcoma) and brain (neuroblastoma). There is risk of developing transitional cell carcinoma of the bladder in adolescents and young adults. Some individuals may have benign growths (papillomata) on their face and near their genitals.

Diagnosis and Genetics of Costello Syndrome

Costello syndrome is diagnosed after evaluation by a doctor who is familiar with this condition. The evaluation should include:

• Detailed family history
• Medical history
• Physical exam

Genetic testing is also useful in making this diagnosis. Most patients with Costello syndrome have a change (mutation) in the HRAS gene.

Typically, each person has two copies of each gene in their genetic makeup. One copy of the HRAS gene is passed down from their father and the other copy is passed down from their mother. With Costello syndrome, a person has a change (mutation) in one copy of the HRAS gene. Males and females are equally affected. Most often, the mutation happens for the first time in the affected person. There is usually no family history of the condition. There is nothing parents of an individual with Costello syndrome did or didn’t do to cause this genetic change.

Most people with Costello syndrome do not have children. If someone with Costello syndrome were to have children, each of their future children would have a 1 in 2, or 50%, chance of inheriting the syndrome.

Treatment and Management

Treatment

There is no “cure” for Costello syndrome. There are treatments and therapies to help with the diagnosis. Each treatment plan is made for the patient, based on their medical issues.

• For those with heart issues, they receive similar treatment to those who have the same heart defect but do not have Costello syndrome.
• For those with delayed development, treatment early in life may include physical, occupational, and / or speech therapy.
• Children may need an Individualized Education Plan (IEP) in school.
• Infants with severe feeding issues may need surgery and / or tube feeding.
• Some people with delayed growth may need growth hormone therapy.
• Those with neurological symptoms may need surgery or use medication.

Management

Children should see their primary care doctor on a routine basis so they can:

• Get additional testing (ultrasounds and urinalysis) to screen for tumors
• Check their growth and development
• Check for neurological symptoms, seizures and skeletal problems

Individuals with Costello syndrome are recommended to see a multidisciplinary team that could include specialists in genetics, cardiology, neurology, dermatology, endocrinology, gastroenterology and ophthalmology.

Prognosis for Patients with Costello Syndrome

Costello syndrome is a lifelong condition. Life expectancy often depends on the how severe the heart defect is. It also depends on the other medical complications the patient has.

Costello Syndrome Resources

• RASopathies Network
• Costello Syndrome Family Network
• International Costello Syndrome Support Group