Costello syndrome is a congenital multisystem disorder caused by a heterozygous germline mutation in HRAS, a proto-oncogene on chromosome 11p15. The majority of patients with Costello syndrome have a de novo autosomal dominant mutation that leads to dysregulation of the Ras / mitogen-activated protein kinase (MAPK) pathway, which regulates cellular differentiation and proliferation.

The syndrome presents with characteristic coarse facial features, distinctive hand posture, intellectual disability, severe feeding difficulty, failure to thrive, short stature, cardiac problems, and a predisposition to neoplasia.

Costello syndrome is very rare: approximately 300 patients have been reported. Boys and girls are equally affected.