Costello syndrome is a genetic disease that affects a range of systems.
It affects various parts of the body and is characterized by loose folds of skin, poor muscle tone and other problems.
Further complications include the development of malignant and nonmalignant tumors, heart defects, and abnormal heart muscle growth.
Costello syndrome, also known as faciocutaneoskeletal (FCS) syndrome is thought to affect 200 to 300 people worldwide, but more cases may remain undiagnosed.
- Costello syndrome is extremely rare, affecting between 200 and 300 people worldwide.
- It can lead to delayed development, intellectual impairment, a large head and mouth with low ears, and loose skin.
- Costello syndrome also causes problems with the heart. It is a genetic condition that affects a range of bodily systems.
- There is no current cure and no specific treatments for the condition. Treatment aims to relieve different aspects of the syndrome, such as hypertrophic cardiomyopathy and special education to support learning difficulties.
Signs and symptoms
Most of the signs of Costello syndrome are not noticeable at birth, but they appear as a child starts to grow.
Birth weight is usually normal or a little above average, but the infant will grow more slowly than most children.
- short height and slow growth
- intellectual disability
- developmental delay
- difficulty feeding in infancy
- large head
- loose skin, especially on the hands and feet
- deep creases on the palms of the hands and soles of the feet
- low ears, thick earlobes, or both
- flexible joints
- large mouth
- the surface of face feels rough
- heart problems, including abnormal heart rhythm
- dental problems
- tight Achilles tendon
- thick calluses and toenails
Costello syndrome is a complex, multisystem condition, and it can lead to various complications.
Infants may be unable to feed orally until the age of 2 to 4 years, or around the same time that they start to speak.
Cardiovascular problems often appear from early childhood, although symptoms may not show until later. These include congenital heart defects and cardiac hypertrophy. The person may experience tachycardia, or a rapid heartbeat, and arrhythmias, or irregular heart rhythms.
Macrocephaly, or overgrowth of the brain, has been noted in 50 percent of patients. This can lead to a Chiari malformation, a structural defect in the brain found in 32 percent of individuals, according to one study. Seizures appear to affect between 20 and 50 percent of individuals with the condition.
Two other genetic conditions with similar symptoms are Noonan syndrome and cardiofaciocutaneous syndrome (CFC). The overlapping symptoms make it harder to diagnose Costello syndrome during infancy.
Costello syndrome is a genetic disorder resulting from mutations in the HRAS gene. This is the gene that instructs the body to produce a protein known as H-Ras. H-Ras aids cell growth and division.
The HRAS gene mutations that occur in Costello syndrome cause cells to grow and divide all the time, not only when they have been instructed to do so.
This can lead to both cancerous and noncancerous tumor growth, and probably underlies the other symptoms.
The HRAS gene mutation can also affect the production of elastic fibers in tissue. These fibers are vital to structures such as the lungs, skin, and large blood vessels, including the aorta.
The fibers are important for keeping hair and skin strong and preventing early breakage and for maintaining the integrity and strength of blood vessels and lung tissue.
Only one copy of the mutated HRAS gene needs to be inherited for Costello syndrome to develop. This type of gene inheritance is known as autosomal dominant.
Most cases of Costello syndrome stem from new mutations, where there is no family history of the condition.
Costello syndrome is very rare, so it is unlikely that a doctor would suspect it at once.
A physician will start by assessing the child's height, the size of the head, and birth weight.
The next stage involves molecular genetic testing. Sequence analysis is carried out on the HRAS gene to see if there is a mutation that relates to Costello syndrome.
There is no cure for Costello syndrome, nor any specific treatment, but aspects of the syndrome, for example, the heart conditions, hypertrophic cardiomyopathy, can be treated specifically.
Ways of helping the individual to manage the condition include:
- helping a child to overcome feeding difficulties during infancy
- treatment for heart problems
- providing special education
Researchers are looking for an effective way of treating the condition at a genetic level.
Other interventions include:
- occupational and physical therapy
- surgery to lengthen the Achilles tendon
- removal of papillomas with cryotherapy
The life expectancy of a person with Costello syndrome has not been formally studied. Studies show that if a fatality occurs, it is likely to result from a complication, such as a heart problem.