What is Costello Syndrome

Costello syndrome is a rare genetic disorder characterized by developmental delays, intellectual disability, distinctive facial features, and an increased risk of certain types of tumors. It is caused by specific mutations in the HRAS gene, which affects the signaling pathways responsible for cell growth and division throughout the body.

What are the primary symptoms of Costello syndrome?

Because Costello syndrome affects the RAS-MAPK signaling pathway, it can impact multiple organ systems simultaneously. Patients often present with failure to thrive in infancy, cardiac abnormalities (such as hypertrophic cardiomyopathy or arrhythmias), and characteristic skin findings, including deep palmar creases and loose, redundant skin. Among the 13 members currently sharing their experiences on DiseaseMaps.org, many report that managing these multisystem symptoms requires a coordinated team of specialists.

What causes Costello syndrome?

Costello syndrome is caused by a germline mutation in the HRAS gene. This gene provides instructions for making a protein that acts as a molecular switch, turning cell growth and division on and off. In individuals with Costello syndrome, this switch is essentially "stuck" in the on position, leading to the overgrowth or abnormal development of various tissues.

How common is Costello syndrome and who does it affect?

Costello syndrome is extremely rare, with an estimated prevalence of approximately 1 in 300,000 to 1 in 1.25 million individuals. There is no known geographic, ethnic, or gender-based predisposition. While most cases occur sporadically (as a new mutation in the individual), the condition is inherited in an autosomal dominant pattern, meaning a person with the condition has a 50% chance of passing the mutation to their offspring.

How is Costello syndrome differentiated from similar conditions?

Costello syndrome is part of a group of conditions known as "RASopathies," which share similar genetic mechanisms. Key clinical features that help distinguish it from related conditions like Noonan syndrome or Cardiofaciocutaneous (CFC) syndrome include:

• A significantly increased risk of malignancies, particularly rhabdomyosarcoma and bladder cancer.


• Distinctive macrocephaly (larger head size) and coarse facial features.


• Significant feeding difficulties requiring early nutritional intervention.


• Developmental delay and intellectual disability, which are present in nearly all diagnosed cases.

Next steps

• Consult with a clinical geneticist to confirm the diagnosis through molecular genetic testing.


• Establish a multidisciplinary care team, including a pediatric cardiologist and an oncologist for routine tumor surveillance.


• Connect with the Costello syndrome community on DiseaseMaps.org to share resources and experiences with other families.


• Visit the Costello Syndrome Family Network for condition-specific support and updated clinical guidelines.

Medical disclaimer: This content is for informational purposes only and does not constitute professional medical advice, diagnosis, or treatment; always seek the advice of your physician or other qualified health provider.

References

• NIH Genetic and Rare Diseases Information Center (GARD): Costello Syndrome Overview.


• Orphanet: Costello Syndrome (ORPHA:207).


• Online Mendelian Inheritance in Man (OMIM): #218040 (Costello Syndrome).


• Costello Syndrome Family Network (CSFN).