Winchester Syndrome

In the course of normal life there is a continuous recycling process of building new materials and breaking down old ones ready for disposal. This activity takes place in a special part of the body’s cells called the lysosome. Molecules are also secreted into their surroundings to form a meshwork of macromolecules called the extracellular matrix. This process requires a series of biochemical tools called enzymes.

Normally the breakdown of various components of the extracellular matrix are carried out by the enzyme matrix metallopeptidase 14. This enzyme also switches on (activates) another enzyme called matrix metallopeptidase 2. Matrix metallopeptidase 2 is important for a variety of body functions, including bone remodelling, a normal process in which old bone is broken down and new bone is created to replace it.

In people with Winchester syndrome, matrix metallopeptidase 14 is not produced or does not function normally which results in the build-up various components of the extracellular matrix and a reduction of matrix metallopeptidase 2. When there is not enough matrix metallopeptidase 2 signs and symptoms of Winchester syndrome begin. Initially babies may show little sign of the disease but it becomes more apparent as more and more symptoms start to appear as they grow.

Winchester syndrome is an autosomal recessive disease this means that both parents must carry the same affected gene and each pass this same affected gene to their child. People probably carry from 5 to 10 genes with mutations in each of their cells. Problems happen when the particular gene is dominant or when a mutation is present in both copies of a recessive gene pair.

Genes are the unique set of instructions inside our bodies that make each of us an individual. They are the blueprint for our growth and development, as well as controlling how our bodies function. Genes are carried on structures called chromosomes and it is usual to have 23 pairs. A child will inherit half of the chromosomes from the mother and the other half from the father resulting in 23 pairs. 22 of these pairs look the same in both males and females. Pair 23 are the sex chromosomes, and this is the pair that differ between females and males. The X chromosome is inherited from the mother and the Y chromosome is inherited from the father. More information about inheritance is available in our publication.

For each pregnancy the chances of a baby inheriting Winchester syndrome are completely independent of whether a previous child was affected with Winchester syndrome. With each pregnancy there is a 1 in 4 chance that the baby will be affected by Winchester syndrome.

All parents of children with Winchester syndrome can benefit from genetic counselling, the counsellor can provide advice on the risk to close relatives and to suggest whether the wider family should be informed. To find out during a pregnancy, if the baby is affected by Winchester syndrome, screening tests can be arranged early on during a pregnancy for those families who already have a child with Winchester syndrome.

Where only one parent is a carrier, they can opt for carrier screening but it is not 100% reliable or accurate and is not possible in all cases. Amniocentesis and chorionic villus sampling are both available during the pregnancy to find out if the baby is affected by Winchester syndrome.

It is estimated that nearly 6% of the UK population (around 3.5million people) will be affected by a rare disease at some point in their lives. A single rare disease may affect up to about 30,000 people however the vast majority of rare diseases affect far fewer than this.

Between 1969-2001, only 12 cases of Winchester syndrome were reported worldwide. Those identified with the syndrome have included people of Mexican, Indian, Puerto Rican and Iranian descent. Winchester syndrome appears to be more common in females than males with a female to male ratio of 3:1.

Onset of Winchester syndrome varies from 3 months to 22 years, but typically the syndrome becomes apparent around the age of two years. In most cases, intellectual ability does not appear to be affected. Heart murmurs and ECG changes have been reported.

Appearance

Growth restriction and marked short stature is characteristic of children with Winchester syndrome. This is probably due to the deteriorating changes taking place in the spine bones (vertebrae) of the backbone and the long bones of the limbs. Facial features of children with Winchester syndrome are described as coarse. They may have a protruding forehead, large flat nose, an enlarged tongue, thickened lips and overgrowth of the gums. Facial features may become coarser as the disease progresses over time. The skin may be thickened and brownish (pigmented) and may also have a leathery consistency. Particularly on the trunk, the skin may be thickened with pigmentation and excess body hair (hirsutism). Nodules under the skin, particularly on the arms and thighs may develop.

Bones and Joints

The most characteristic feature of Winchester Syndrome is osteolysis, ‘dissolving bones’. This is most noticeable in the small bones of the hands and feet and may lead to their total disappearance. There may also be significant bone deformities due to changes occurring in the joints. These changes can be found in the joints of the hands, feet, knees, shoulder, elbow and hip joints. They can cause pain especially during movement and limited mobility. In most cases of Winchester syndrome, bone loss begins in the hands and feet, causing pain and limiting movement. Bone abnormalities later spread to other parts of the body, with joint problems occurring in the elbows, shoulders, knees, hips, and spine. Most people with Winchester syndrome develop low bone mineral density (osteopenia) and thinning of the bones (osteoporosis) throughout the skeleton. These abnormalities make bones brittle and more prone to fracture.

Eyes

Clouding of the cornea is sometimes seen in people with Winchester syndrome and can lead to significant visual disability especially as the disease progresses. Severe corneal clouding may reduce sight, especially in dim light. Some people cannot tolerate bright lights. A loss of night vision is common which may also be due to damage of the retina. Glaucoma, abnormally high pressure in the eye, may occur and cause damage to the retina and results in optic nerve atrophy.

Dental

Good dental hygiene is very important for children with Winchester syndrome, teeth should be well cared for to avoid tooth decay, pain and extractions. Usually teeth are widely spaced, poorly formed with fragile enamel and more than the normal number of teeth for the age. Cleaning around the mouth with a small sponge or a stick soaked in mouthwash will help keep the mouth fresh and avoid bad breath. If the water in your area has not been treated with fluoride, speak with your dentist about including fluoride tablets or drops as part of the dental management plan. Dribbling is a common problem and can soak through clothes causing soreness, to prevent this choosing a bib that is plastic backed.

It may be safer for any treatment to be carried out in hospital. If teeth need to be removed under anaesthetic this should be carried out in hospital under the care of an experienced anaesthetist and never in the dental surgery. It is important to inform the dentist about heart problems when discussing any treatment. This is because certain bacteria in the mouth may get into the blood stream and cause an infection on the heart valves. In most cases antibiotics are usually prescribed before and after any dental treatment.

At present there is treatment for symptoms as they arise, but no cure for the underlying disease. More information on supportive care treatments for people with MPS and related diseases can be found in the treatments section.

For an up-to-date list of current UK based trials taking place visit Be Part of Research (resource provided by the National Institute for Health Research). For an international search visit Clinical Trials (resource provided by the U.S. National Library of Medicine).

This resource provides information on trial status including recruiting, completed or withdrawn and worldwide trial locations. To find out more about past or current trials speak to your doctor and learn about the risks and potential benefits.

The MPS Society is the only UK charity at the forefront of supporting people and families affected by MPS and related diseases. Our extensive support services offer you a wide range of support and resources.

The team can advise and sign post you to adequate needs-led support and services in your local area as well as social care, home adaptions, education and much more.

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