Costello syndrome is a rare genetic disorder that affects various areas of the body. Delayed physical development and mental retardation are the most distinguishing characteristics of the condition. A child with Costello syndrome might have a high birth weight, however the other signs are not noticeable until the child starts to grow.

Also known as FCS syndrome (faciocutaneoskeletal syndrome), Costello syndrome affects an estimated 300 people worldwide, with more possibly going undiagnosed.

Costello syndrome was discovered in 1977 by a Pediatrician from New Zealand called Dr Jack Costello. The disorder can lead to further complications, such as the development of malignant and non malignant tumors, along with certain heart defects and abnormal heart muscle growth. What are the Signs and Symptoms of Costello syndrome A symptom is something the patient feels or reports, while a sign is something that other people, including the doctor detects. A headache may be an example of a symptom, while a rash may be an example of a sign.

The birth weight of a child with Costello syndrome is usually normal or a little above average, however they will grow at a slower rate than most children. It is not until the child starts to grow, that signs of Costello syndrome start to develop, some of these are: Short in height and slow growth Mental deficiency Flatter nasal bridge Curly hair Difficulty sucking Larger head Skin is loose Low ears and/or thick earlobes Thicker lips Surface of face feels rough Misaligned eyes (strabismus) Pigmentation of skin is dark Short neck Squint Heart problems/abnormal heart rhythm Please note that there are two other genetic conditions that share similarities in symptoms to Costello syndrome. Noonan syndrome and CFC (cardiofaciocutaneous) share many characteristics with Costello syndrome, making Costello syndrome harder to diagnose during infancy. What are the Causes of Costello syndrome As previously mentioned, Costello syndrome is a genetic disorder. It is caused by mutations in the HRAS gene. It is this gene that instructs the body to produce a protein (H-Ras) that aids cell growth and division.

The HRAS gene mutations that occur in Costello syndrome result in cells growing and dividing all the time rather than when they have been instructed to do so. This can lead to tumor growth (cancerous and non-cancerous) and is believed to be the cause of the visual signs listed above. In Costello syndrome, the HRAS gene mutation can also negatively affect the production of elastic fibres in 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. Nearly every case of Costello syndrome has been caused from new mutations where there is no family history of the condition. How is Costello syndrome Diagnosed? There are two stages involved in diagnosis of Costello syndrome. First there is the clinical diagnosis, which involves assessing the physical characteristics of the patient to see if they meet certain criteria (examples are: height, size of head and birth weight).

As a method of diagnosis has not yet been perfected, there is a second stage which involves molecular genetic testing. The HRAS gene is put under sequence analysis to look for mutations. If a HRAS mutation is not detected, the clinical diagnosis would need to be reassessed. What are the Treatment Options for Costello syndrome? At present there is no way of curing Costello syndrome, nor is there a particular way of treating the condition. Nevertheless there are ways of helping the child manage their condition, these include: Helping the child with feeding difficulties during infancy Treatments for any heart problems that develop Providing special education for the child An effective way of treating the condition at a genetic level is currently being researched. In 2005, at a meeting for the American Society of Human Genetics, a new Progeria treatment was presented. The treatment involved the use of FTI (farnesyltransferase inhibitor) on H-Ras, it was after this presentation that FTI was considered as a possible treatment for Costello syndrome.

Other medications that could possibly help treat Costello syndrome include: MEK inhibitor Lovastatin As Costello syndrome is not a common condition there are not that many test subjects for clinical trials. Because of this, researchers say that only one medication can be tested effectively at a time. This along with the need to raise research funding means that it could be a while before an effective treatment is brought onto the market.

Written by Mike Paddock