Costello Syndrome

What is Costello syndrome?

Costello syndrome is a rare disorder that affects many different body systems, but the disorder is especially characterized by delayed development and intellectual disability, loose folds of skin (which are especially noticeable on the hands and feet), unusually flexible joints, and distinctive facial features including a large mouth.

In addition to these problems, individuals affected by Costello syndrome are also at an increased risk of developing certain tumors, both cancerous and noncancerous and including papillomas near the mouth or anus, rhabdomyosarcoma, or neuroblastoma.

What causes Costello syndrome?

Costello syndrome is caused by mutations in the HRAS gene. These mutations result in a production of an abnormal H-Ras protein that leads to continuous cell growth and division.

Even though more individuals with Costello syndrome get this gene mutation spontaneously, it does follow an autosomal dominant inheritance pattern.

What are the symptoms of Costello syndrome?

In addition to the characteristic features of Costello syndrome listed above, other signs and symptoms of this disorder include the following:

• Heart problems, such as an abnormal heartbeat, structural heart defects, and hypertrophic cardiomyopathy
• Larger than average size at birth, but slower growth later and a short stature
• Difficulties feeding
• Tight Achilles tendons
• Weak muscle tone
• Skeletal abnormalities
• Chiari I malformation
• Dental and vision problems
• Coarse facial features

These signs and symptoms can overlap significantly with other genetic conditions.

How is Costello syndrome diagnosed?

Costello syndrome is diagnosed using a thorough clinical examination and specific diagnostic criteria that has been developed. However, since Costello syndrome shares many similar symptoms with other conditions, as noted above, molecular genetic testing for mutations in the HRAS gene is available to confirm a diagnosis.

What are the available treatments for Costello syndrome?

Unfortunately, there is currently no cure for Costello syndrome, so treatment is symptomatic and supportive. The cardiac abnormalities present in Costello syndrome need to be treated with certain medications, such as beta-blockers, calcium channel blockers, or antiarrhythmic medications, or surgical interventions.

Bracing, occupational therapy, and physical therapy may also be beneficial for affected individuals, to alleviate some of the complications associated with the physical abnormalities in the disease.

Where can I find more information on Costello syndrome?

• National Organization for Rare Disorders (NORD)
• U.S. National Library of Medicine