Definition
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
< swipe to see entire table >
Synonym | |
Gen | HRAS |
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) |
< swipe to see entire table >
Diagnosis
Diagnosis
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
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
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.