Costello's Syndrome

Costello’s Syndrome (CS), also known as Faciocutaneoskeletal syndrome (FCS), is a disease caused by a genetic mutation of the HRAS gene that affects between 200 and 300 people world wide.
CS has a multitude of different symptoms which overlap with the symptoms associated with Noonan’s syndrome and with Cardiofaciocutaneous syndrome (CFC syndrome), therefore in order to confirm a diagnosis of CS, there must be a mutation of the HRAS gene, and not associated genes. CS is an autosomal dominant disorder (meaning only one altered gene is required) but caused by a mutation and is seldom passed on to children and therefore not considered a hereditary disease.
            The mutation of the HRAS gene, wich controls cell growth,  may be responsible for many of the symptoms, but others have yet to be explained. The symptoms that involve unregulated cell growth are the spontaneous formation of both cancerous and noncancerous tumors (15% lifetime risk for malignant tumors), along with Hypertrophic Cardiomyopathy (HCM). approximately 85% of CS patients have a cardiac abnormality, with 61% having HCM. Most of those with CS /HCM have a moderate presentation of HCM. In some cases “Burnt out” HCM may present. Other symptoms include delayed development, loose folds of skin( Figure 2), short stature, musculoskeletal issues, and prominent coarse facial features (Figure 1).There are also secondary complications which can occur as a result of the directly associated symptoms of CS.
            Unfortunately there is no cure and the prognosis for patients with CS is poor. There are many treatment options for the symptoms. Treatment can include surgical removal of excess cell growth (tumors and excess skin), physical therapy, and special education for the developmental disabilities. CS treatment is best handled in a multidisciplinary maintenance allowing for input from a variety of specialists. This usually takes place in an academic childrens hospital.
            The HCMA is happy to assist with cardiac related issues, however the Costello Syndrome Family Network (CSFN) has greater resources for multidisciplinary care.

Figure 1: Facial view of young boy with Costello’s syndrome

Figure 2: Loose folds of skin in foot of Costello’s syndrome patient
“ Costello Syndrome.” U.S. National Library of Medicine Accessed March 13th, 2018.
Karen W Gripp, MD, FAAP, FACMG and Angela E Lin, MD, FAAP, FACMG. “Costello Syndrome” National Center for Biotechnology Information Accessed March 13th, 2018.
            Mike Paddock. “Costello syndrome: Causes, symptoms, and treatment” 28 July 2017
Costello Syndrome Family Network Website Accessed March 29th, 2018