Costello syndrome (OMIM #218040) is an autosomal-dominant, hereditary developmental disorder with a distinct phenotype (see the clinical features) and a greatly increased risk of cancer.

Key Data

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Gene product HRAS
Function Ras signaling pathway
Heredity Autosomal dominant
Prevalence Rare
Genotype-phenotype correlation The G12A-HRAS mutation appears to be associated with the highest risk of cancer.
Penetrance  100% (for to the syndrome as opposed to developing the neoplasia)
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The diagnosis is made clinically based on the characteristic features (see below). In many cases, evidence of an HRAS mutation can be detected by sequence analysis or targeted mutation analysis.

Differential Diagnoses

  • Noonan syndrome

  • CFC syndrome

  • Neurofibromatosis type 1

  • Legius syndrome

Clinical Presentation

Clinical Presentation

In addition to the typical features of Noonan syndrome, children with Costello syndrome exhibit pronounced mental disability, feeding problems, frequent hypertrophic cardiomyopathy, tachycardia, typical skin and hair changes, and more course facial features. In addition, there is also a high risk of cancer, particularly embryonal rhabdomyosarcomas, neuroblastomas, and early-onset bladder cancer. Approximately 15% of patients develop a tumor by the age of 20.

Therapeutic Considerations

The cancer treatment should be discussed with the principal investigator of the respective study. In theory, it may be worth considering treatment with an MEK inhibitor.

Surveillance Recommendations

Surveillance Recommendations

  • From 0 to between 8-10 years of age: physical examination and ultrasound of the abdomen and pelvis (possibly along with an X-ray of the thorax) every 3-4 months

  • From the age of 10: annual urinary analysis

Additional Information

Open Clinical Trials / Registries

There are currently no open clinical trials/registries for patients with Costello syndrome that we can recommend to you for more information.

Support Groups