Costello syndrome is a rare genetic disorder that affects various parts of the body. Delayed physical and mental development are the most distinguishing characteristics of the condition.
Further complications can develop, such as the development of malignant and nonmalignant tumors, heart defects, and abnormal heart muscle growth. Common heart problems include hypertrophic cardiomyopathy, which is an enlargement of the heart that weakens the heart muscle, abnormal heart beats, or arrhythmia, and other structural defects.
Costello syndrome affects an estimated 350 people worldwide, but there may be more cases that are undiagnosed.
Costello syndrome was discovered in 1977 by a pediatrician from New Zealand called Dr. Jack Costello.
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Signs and symptoms of Costello syndrome
Most of the signs of Costello syndrome are not noticeable at birth, but they appear as a child starts to grow.
The birth weight of a child with Costello syndrome is usually normal or a little above average, but they will grow at a slower rate than most children.
Some of these symptoms are:
A person with Costello syndrome may have a higher than average birth weight, but most symptoms do not appear until later.
- Short height and slow growth
- Cognitive deficiency
- Flatter nasal bridge
- Curly hair
- Difficulty sucking
- Large head
- Loose skin
- Low ears, thick earlobes, or both
- Thicker lips than usual
- The surface of face feels rough
- Dark Pigmentation on skin
- Heart problems, including abnormal heart rhythm.
Two other genetic conditions that have similar symptoms to Costello syndrome are Noonan syndrome and cardiofaciocutaneous syndrome (CFC). The overlapping symptoms make it harder to diagnose Costello syndrome during infancy.
Causes of Costello syndrome
Costello syndrome is a genetic disorder that is caused by 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.
In Costello syndrome, the HRAS gene mutation can also have a negative effect on the production of elastic fibers in tissue.
Elastic fibers are vital to structures such as the lungs, skin, and large blood vessels, such as 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 in order for Costello syndrome to develop. This type of gene inheritance is referred to as autosomal dominant.
Most cases of Costello syndrome stem from new mutations where there is no family history of the condition.
How is Costello syndrome diagnosed?
After looking for physical signs of Costello syndrome, a doctor will look for a mutation in the HRAS gene.
There are two stages involved in the diagnosis of Costello syndrome.
First, the physician will assess 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.
Treatment for Costello syndrome
There is no cure for Costello syndrome, nor any specific treatment, but aspects of the syndrome, for example 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
- Treatments for heart problems
- Providing special education
An effective way of treating the condition at a genetic level is currently being researched.
Medications that could help treat Costello syndrome include lovastatin. A study of children with Costello syndrome and similar disorders, lovastatin was shown to improve verbal and nonverbal memory and visual attention.
As Costello syndrome is not a common condition, there are few test subjects for clinical trials. Therefore, only one medication can be tested effectively at any time. This, together with the need to raise research funding, means that it could be some before an effective treatment is brought onto the market.