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Costello Syndrome [Q87.0]

OMIM numbers: 218040, 190020 (HRAS)

Dr. rer. biol. hum. Soheyla Chahrokh-Zadeh

Scientific Background

The Costello syndrome belongs to the group of RASopathies and is a highly rare disease with an estimated incidence of 1 in 300,000 (United Kingdom) or 1 in 1,230,000 (in Japan). Inheritance is autosomal dominant.

Signs typical for RASopathies such as prenatal neck edema, postnatal facial dysmorphism, short stature, mild to moderate intellectual disability and cardiac defects are found also in the Castello syndrome. Main feature is perinasal and/or perianal benign cutaneous papillomata. Furthermore increasing pigmentation of the skin is characteristic.

In 90% of all cases, the ultrasound shows a severe polyhydramnios or neck edema. Perinatally, edemas are substantially responsible for a heavy birth weight, followed by a severe failure to thrive as a result of severe feeding difficulties. Cardiac defects mainly include hypertrophic cardiomyopathy (HCM) and atrial septal defects in combination with arrhythmias. The risk of the development of solid tumors (especially rhabdomyosarcoma) during childhood or early adult age is increased to approximately 15%.

The only gene causing the Costello syndrome is the HRAS gene. 80–90% of all mutations affect the amino acid glycine in the position 12 in exon 2 of the protein GTPase HRas. Occasionally, other mutations of the HRAS gene are described.