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Costello syndrome

Also known as: Faciocutaneoskeletal syndrome (FCS)

Background

Costello syndrome (CS) is a rare genetic condition. It is usually diagnosed early in life because of severe feeding difficulty, or a difference about the way the heart is formed (congenital heart disease).

Credits

Last updated August 2018 by Professor Bronwyn Kerr, Consultant Clinical Geneticist and Dr Emma Burkitt-Wright, Consultant Clinical Geneticist, Genomic Medicine,  Manchester University NHS Foundation Trust, Manchester, UK.

Although great care has been taken in the compilation and preparation of all entries to ensure accuracy, we cannot accept responsibility for any errors or omissions. Any medical information is provided is for education/information purposes and is not designed to replace medical advice by a qualified medical professional.

What are the symptoms?

Babies with CS are usually large at birth, and facially unremarkable.  Polyhydramnios (excessive amniotic fluid) is common. Nearly all children with CS have severe feeding difficulties, and reflux (vomiting after feeding). Some babies require tube or gastrostomy feeding. Infants may be irritable and hypersensitive to sound and touch. These features usually improve after age two.

Differences about the heart (see entry Heart Defects) can include hypertrophic cardiomyopathy (see entry Cardiomyopathies), pulmonary stenosis or other abnormalities and irregular heart rhythms.

Rarely, cardiomyopathy may be very severe in the newborn period.  In this small group of very ill babies, hypoglycaemia (low blood sugar) and breathing difficulties are common.

Over time, facial features can include macrocephaly (large head), low-set ears with large, thick lobes and thick lips. Excessive loose skin develops on the palms, fingers and soles, which may thicken over time. Papillomata (small wart-like growths) may occur around the mouth and nostrils.

Joint differences are common, including an unusual posture of the wrists. Scoliosis (curvature of the spine) is also common. People with CS are usually short.

Developmental milestones are delayed. Most children will learn to walk and talk, but the age of doing these is usually delayed, and not all children will acquire age-appropriate skills. Although developmental delay is nearly always present, it is variable. Many children attend mainstream school in the infant and primary years.

Some individuals with CS have developed cancer; this cancer risk appears to be greatest in the first years of life, particularly for a tumour of muscle called embryonal rhabdomysosarcoma.  Although this can start in any skeletal muscle, it is commonest in the abdomen and pelvis.  An increased risk of bladder cancer occurs from adolescence.

What are the causes?

Costello syndrome is caused by a mutation in a gene called HRAS, which is important in a pathway in cells called the Ras-MAPK pathway. As a result, it is sometimes called a "Rasopathy".

How is it diagnosed?

Costello syndrome is diagnosed by a blood test which tests the gene HRAS for mutations.

A number of other syndromes, particularly other Rasopathies (including Cardiofaciocutaneous syndrome and Noonan syndrome), conditions associated with being large at birth and storage diseases can share certain features with CS. A diagnosis of CS should be considered in patients where these conditions are suspected, but not confirmed.

How is it treated?

Treatment in Costello syndrome is focussed on the associated medical complications. Care should be overseen by a regional genetic service, and for developmental aspects, by a multi-disciplinary team. The cancer risk requires rapid investigation of persisting symptoms, and annual urinalysis from age 10. A regular examination of the abdomen (tummy) and three to four monthly ultrasounds of abdomen and pelvis are recommended until 8 to 10 years.

Some children with CS have growth hormone deficiency. Growth should be monitored using CS charts. If the growth rate is decreasing, this should be discussed with a paediatric endocrinologist.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
Most cases of CS are sporadic (the first in a family). Parents should be tested when an HRAS gene change is found in their child. If a parent has the gene change, the chance of each further child being affected would be 50 per cent. If parental testing is normal, the chance of a second affected child is low.

Prenatal diagnosis
Prenatal diagnosis is available, and undertaken by some families for reassurance in subsequent pregnancies.

Is there support?

Costello Kids

Tel: 0845 226 0163
Email: via website
www.costellokids.com

The Group is a Registered Charity in England and Wales No. 1085605. It offers information and support to families affected by Costello Syndrome or CFC Syndrome. 

Group details last updated August 2018.