Tumor predisposition in Costello syndrome

Costello syndrome (CS) is a rare congenital anomaly syndrome. Although it may be classified as an "overgrowth" syndrome due to slightly increased birth weight and relative macrocephaly, it is characterized by severe postnatal failure to thrive and short stature. Patients with CS have an increased risk for malignant tumors, a hallmark of several model overgrowth syndromes. The most common tumor in CS is rhabdomyosarcoma (RMS), followed by neuroblastoma and bladder carcinoma. The occurrence of bladder carcinoma in adolescents is distinctly unusual as this is typically a neoplasm of older adults and is not seen with increased frequency in other tumor predisposition syndromes. The increased tumor frequency in CS led to the proposal of a screening protocol, consisting of abdominal and pelvic ultrasounds, and urine studies for catecholamine metabolites and hematuria. It has since become apparent that patients with CS have an increased excretion of catecholamine metabolites in urine without the presence of an identifiable catecholamine secreting tumor. Thus, the urine assay for catecholamines is unhelpful as a screening test for neuroblastoma and should not be used in this population. The benefit of abdominal and pelvic ultrasound and urinalysis for hematuria as screening tests remains to be shown. A timely diagnosis of CS is a necessary prerequisite for awareness of the increased tumor risk. Once a malignancy has been identified, treatment should follow standard protocols. Additional medical problems characteristic for CS, such as hypertrophic cardiomyopathy and arrhythmia, need to be considered and addressed appropriately.