Costello syndrome

Costello syndrome is a very rare malformative syndrome associated with RASopathies. It is characterized by magnified, characteristic facial features, lack of talent, postnatal growth retardation, skin abnormalities and heart defects.

The dermatological findings include excess skin (neck, hands, feet), hyperkeratosis of the hands, acanthosis nigricans, dark skin and papillomas. A failure to thrive in the first few months of life result in dwarfism, which later is normalized by normal weight gain.

A majority of those affected suffer from cardiomyopathy, and less often other internal organs are involved. In most cases, mild to moderate mental retardation can be detected. The characteristic facial features include a prominent forehead, flat nose root, wide mouth with inflated lips, and an epicanthus.

Patients have an increased risk for the formation of solid tumors. The most common are rhabdomyosarcomas, bladder tumors, and neuroblastomas. About 15% of the patients get cancer before the age of 20. So far, about 220-300 cases have been described. The cause was in most cases a new mutation in the HRAS gene at the locus 11p15.5. The prognosis is dependent on the possible occurrence of a malignant tumor and the severity of the cardiomyopathy.