What are the other Names for this Condition? (Also known as/Synonyms)

• Faciocutaneoskeletal Syndrome
• FCS Syndrome

What is Costello Syndrome? (Definition/Background Information)

• Costello Syndrome is a rare condition that affects many different parts of the body. Signs and symptoms generally include developmental delay, intellectual disability, distinctive facial features, loose folds of extra skin (especially on the hands and feet), and unusually flexible joints
• Affected people may also have heart abnormalities such as tachycardia, structural heart defects, and hypertrophic cardiomyopathy. Beginning in early childhood, people with Costello Syndrome additionally have an increased risk to develop certain cancerous and noncancerous tumors
• Costello Syndrome is caused by changes (mutations) in the HRAS gene. It is considered an autosomal dominant condition, but almost all cases are the result of de novo gene mutations and occur in people with no family history of the condition
• Treatment is based on the signs and symptoms present in each person
• Costello Syndrome belongs to a group of related conditions called the RASopathies. These conditions have some overlapping features and are all caused by genetic changes that disrupt the body's RAS pathway, affecting growth and development
• The features of Costello Syndrome overlap significantly with two of the RASopathies - cardiofaciocutaneous (CFC) syndrome and Noonan syndrome

(Source: Costello Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Costello Syndrome? (Age and Sex Distribution)

• Costello Syndrome is a rare congenital disorder. The onset of symptoms is observed in young children
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Costello Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Costello Syndrome can be reportedly inherited
• Currently, no other risk factors have been clearly identified for Costello Syndrome

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Costello Syndrome? (Etiology)

• Costello Syndrome is caused by changes (mutations) in the HRAS gene
• It is considered an autosomal dominant condition, but almost all cases are the result of de novo gene mutations and occur in people with no family history of the condition

(Source: Costello Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Costello Syndrome?

The signs and symptoms of Costello Syndrome may include:

Very frequently present symptoms in 80-99% of the cases:

• Abnormality of the fingernails
• Acanthosis nigricans
• Concave nail
• Deep-set nails
• Delayed skeletal maturation
• Failure to thrive in infancy
• Hyperkeratosis
• Lack of skin elasticity
• Macrocephaly
• Narrow palate
• Pulmonic stenosis
• Redundant skin
• Short neck
• Ventricular septal defect

Frequently present symptoms in 30-79% of the cases:

Occasionally present symptoms in 5-29% of the cases:

• Coarse facial features
• Generalized hyperpigmentation
• Large earlobe
• Large face
• Low-set, posteriorly rotated ears
• Poor suck
• Renal insufficiency

(Source: Costello Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Costello Syndrome Diagnosed?

Costello Syndrome is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Costello Syndrome?

The complications of Costello Syndrome may include:

• Formation of malignant tumors
• Multiple organ dysfunction
• Sudden death has been reported in many cases

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Costello Syndrome Treated?

There is no cure for Costello Syndrome, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complications that develops.

How can Costello Syndrome be Prevented?

Currently, Costello Syndrome may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Costello Syndrome? (Outcomes/Resolutions)

• The prognosis of Costello Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Costello Syndrome:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/