MARFAN SYNDROME

Marfan syndrome is an inherited disorder of connective tissue which affects many organ systems, including the skeleton, lungs, eyes, heart and blood vessels. This condition, first described by Dr. Marfan in 1896, can affect both men and women of any race or ethnic group. It is estimated that well over 5000 people in the United Kingdom have Marfan syndrome. A syndrome is a collection of physical features which, when they occur together, enable a physician to recognise a certain condition.

Salient features

Ocular:

• subluxation or dislocation of lens
• myopia and unstable refraction
• detachment of retina
• strabismus
• glaucoma

Dental:

• high-arched palate
• crowding of teeth
• Cardiovascular:
• dilatation of ascending (and sometimes descending) aorta
• incompetence of aortic and mitral valves
• aneurysm and dissection of aorta

Skeletal:

• tall thin physique, with long limbs and fingers
• spinal curvature
• flattening of chest (with pigeon or funnel deformity)
• armspan greater than height

What causes Marfan syndrome?

A single abnormal (mutant) gene on Chromosome 15 causes the condition. This abnormal gene controls production of fibrillin, a very fine fibre in connective tissue throughout the body (the "glue and scaffolding of the body"). Most of the time this gene is inherited from a parent who is also affected. However, about 25% of the cases occur when the abnormal gene appears in an egg or a sperm (a "new mutation") and goes on to make an affected child of two unaffected parents.

Marfan syndrome is inherited as an "autosomal dominant" condition. This means that someone with Marfan syndrome has a 50-50 chance that each offspring will inherit the condition. On average, one in ten affected children are seriously affected.

How is Marfan Syndrome diagnosed?

Marfan Syndrome may be difficult to diagnose because signs of the condition vary greatly from one person to the next. Most affected people will not show all the signs and complications of Marfan Syndrome.

Blood and skin tests demonstrating the abnormal gene are becoming available for diagnosis through referral to a clinical geneticist. Pre-natal diagnosis is now available for some families with this condition, especially those families where a mutation (change) in the fibrillin gene has been demonstrated.

In general, Marfan Syndrome is diagnosed after a careful physical examination, particularly focusing on the three main systems involved, i.e. eyes, skeleton, and heart. Certain tests, such as an echocardiogram (a sound-wave picture of the heart) are useful in making the diagnosis. Marfan syndrome patients should have an initial diagnostic echocardiogram which is repeated at regular intervals. An electrocardiogram or chest x-ray is not adequate screening. Skeletal x-rays (mainly chest and back) may be necessary and a careful eye examination, using a slit lamp to detect lens dislocation, is recommended.

People with marfan syndrome should be treated by a physician familiar with the condition, conversant with its effects on all body systems and able to advise on screening of the family. Genetic counselling should be given. There is no cure for this condition yet, but careful medical and surgical management, together with an appropriate lifestyle, can greatly improve prognosis and lengthen life span.

What medical problems are associated with Marfan syndrome?
How they are treated?
Heart

The most serious problems associated with Marfan Syndrome involve the cardiovascular system. The two leaflets of the mitral valve may billow backwards when the heart contracts, a condition called "mitral valve prolapse". This feature may lead to heart failure or be associated with irregularities of the heart rhythm.

The aorta (the main artery carrying blood away from the heart) is generally wider and more fragile in patients with the Marfan Syndrome. This widening is progressive and may result in leakage of the aortic valve or in the development of tears (dissection) in the wall of the aorta. When the aorta becomes widened, medications, for example beta blockers, may be prescribed, followed by surgical repair when the aortic root widens beyond 5.5 cms diameter, or when it becomes torn.

Skeleton

Involvement of the skeleton includes curvature of the spine (scoliosis/kyphosis), abnormally shaped chest ("pectus" deformity), tall stature, and loose jointedness (often causing joint pain and dislocation). Physiotherapy and bracing may be helpful. In certain instances, surgery is indicated.

Eyes

People with Marfan Syndrome are generally near-sighted (myopic). In addition, some have dislocation of the ocular lens and retinal detachment. Glasses may be prescribed to correct visual defects. Surgery may be required.

Lungs

In some cases, pneumothorax (collapse of the lungs) may occur requiring hospital treatment.

Milestones

• 1986 fibrillin was discovered
• 1990 the Marfan Syndrome gene was located on chromosome 15 and found to produce defective fibrillin.
• 1991 the first gene mutations were described and the European Marfan Support Network was founded
• 1992 the National Schools Project commenced and the International Federation of Marfan Syndrome Organisations was formed
• 1993 30 mutations discovered so far
• 1994 the Marfan Association celebrated its tenth birthday