Conditions
The Marfan syndrome is an inherited genetic disorder affecting the production of Fibrillin, a substance found in elastic and connective (fibrous) tissue throughout the body.
Definition and cause
The Marfan syndrome is an inherited genetic disorder affecting the production of Fibrillin, a substance found in elastic and connective (fibrous) tissue throughout the body. The syndrome was first described in 1899 by a French paediatrician Marfan.
Inheritance
This syndrome is inherited as an autosomal dominant, meaning that each parent with the condition has a 50% chance of passing it on to any offspring. Whilst most cases do have a family history of the condition, spontaneous genetic mutation can occur, giving rise to new cases in previously unaffected families. Not all persons with Marfan’s will have exactly the same pattern of characteristics, though most will be similar enough to recognize.
Diagnosis
The basic defect in Marfan’s is the production of poor quality fibrous and elastic tissue. As these tissues are found throughout the body, many problems can arise. The whole skeleton and all joints can be affected, and areas with a high elastic tissue-content are particularly susceptible. At least thirty clinical features have been associated with this syndrome, but no one finding is unique to it.
However, a grouping of major finding is usually enough to make the diagnosis. This essential combination includes
- abnormally long limbs
- dislocated eye lenses
- dilatation of the aortic root
Individual signs in major systems
The following signs are characteristic of Marfan’s, but are found in different degrees of severity in affected persons.
Skeletal system
Marfan patients are very tall, with disproportionately long limbs (arm span exceeding their height), fingers and toes (arachnodactyly). Spinal curvature (scoliosis) and slipping of hypermobile joints may be significant. Chest abnormalities include a protruding or inward-caving chest, either of which may need surgical correction. Flat feet due to weakened arches may cause chronic pain. A very high arched palate with dental malocclusion may lead to speech problems.
Cardiovascular system
The most serious and life-threatening problems arise here and affect the great majority of Marfan patients. The three most serious conditions here are:
- Aortic aneurysm: the aorta is the largest artery in the body: it comes directly from the heart and supplies blood to the whole body. The poor connective and elastic tissue in Marfan’s weakens the walls of the aorta, causing it to stretch. If the weakened part extends backwards into the root of the aorta, the aortic valve may also become stretched and begin to leak, causing symptoms of aortic valve regurgitation. The risk of rupture and sudden death increases as the aorta continues to dilate.
- Aortic dissection: a tear can easily happen in the fragile lining of the distended aorta, especially if the blood pressure is high. Blood can enter this tear, going further and further down the aorta, until a long segment is dissected away. This further weakens the wall, increasing the risk of rupture. Dissection of the aorta usually causes sudden severe pain in the chest, which goes through to the back.
- Mitral valve prolapsed: the mitral valve is the “inlet” valve to the left ventricle of the heart, or main pumping chamber. Weak connective tissue leads to a floppy valve flap which billows up and stops the valve from closing properly, causing a leaky valve. In severe cases, this causes heart failure and rhythm disturbances. The abnormal valve is also more prone to infection (endocarditis)
Eyes
Vision problems are common in Marfan’s, the most common of which is dislocation of the lens due to weak ligaments, which normally anchor the lens.
Extreme nearsightedness is also common, as are cataract (clouding of the lens) and glaucoma (increased pressure within the eye). Weak tissues can also cause the retina to become loosened from the back of the eye.
Lungs
Spinal curvature may cause difficulty breathing. Spontaneous pneumothorax occurs often: a weak spot in the lung allows air to enter the pleural space, causing the lung to collapse partially or even completely. Abnormal lung tissue also predisposes towards emphysema, and asthma and pneumonia may occur more frequently in Marfan’s.
Nervous system
Weakened tissue in the dura, the membrane surrounding the spinal cord, can expand causing headache, pain in the legs, lower back or abdomen.
Pregnancy
Those patients with existing aortic dilatation have an increased risk of aortic rupture and dissection during pregnancy. The extra load on the mother’s cardiovascular system during pregnancy and the increased risk of hypertension are potentially life-threatening.
Diagnostic tests used in the evaluation of a patient will include:
- a detailed family medical history
- a detailed physical examination, with special emphasis on the skeleton, cardiovascular system, lungs and eyes. Specialists in each of these fields will be involved.
- an echocardiogram – either transthoracic or trans-oesophageal – to assess the state of the aorta, and the aortic and mitral valves
- chest x-ray and possibly MRI scan
Definitive genetic testing can be done to identify a Marfan patient beyond any doubt.
Management
The Marfan syndrome cannot be cured, but patients must be actively monitored to prevent complications and to treat them when they do.
Cardiovascular
Regular echocardiograms will monitor the dilatation of the aorta and the functioning of the aortic and mitral valves. Beta-blockers and ACE inhibitors are used to keep blood pressure and pulse rate low, and may help to improve the elasticity of the aorta. If the aorta dilates too rapidly or reaches a certain size or there is significant valve leakage, surgery will be considered. Different operations are done, depending on the problem. Because the abnormal tissues create an extra problem, these operations are best done by experienced surgeons only. In cases of aortic rupture or dissection, surgery may be the only option.
Lifestyle
Strenuous physical activity is discouraged, particularly weight-lifting, body building, rock climbing, surfing and scuba diving. Less strenuous activities, which are usually also prohibited, but will depend on the individual case include squash, running, tennis soccer, biking, lap swimming, motorcycling and horse-riding.
Low intensity, non-competitive activities which are probably safe include
- doubles tennis
- golf
- bowling
- walking or stationary biking
These do not apply to patients who have had aortic root or valve replacement in whom strict blood pressure control and anti-coagulation must be ensured – physical exertion is thus not recommended.
Musculoskeletal
For adolescents, wearing a corrective brace may prevent scoliosis worsening during the growth years. For severe scoliosis (deviation > 40–50°) surgery may be needed to correct spinal or chest deformities: spinal fusion with metal implants is usually done. This is highly complex surgery and should only be done by renowned experts in this field.
Ophthalmic
Here too, because of the special problems in Marfan patients, only surgeons experienced in this field should be consulted. If conservative methods fail or cannot be used, lenses can be implanted in the eye to restore vision lost through lens displacement or cataract formation. Regular screening for glaucoma will ensure that medication is started in good time to prevent permanent damage to the optic nerve. Retinal tears or detachment is often bilateral – treatment will depend on the extent of the lesions.
Pregnancy
Generally, women with Marfan’s are discouraged from becoming pregnant, not only because of the 50% risk of transmission of the gene to offspring, but because of the increased risk to themselves during pregnancy and delivery. The added physiological burden of pregnancy can speed up complications during pregnancy, especially aortic dissection, which could be fatal. Mothers should thus be assessed before conception if possible, and have echocardiograms every 6-10 weeks to monitor aortic diameter. Vaginal delivery under optimal conditions (epidural anaesthesia and suction or forceps delivery without maternal pushing) is often possible.
Outcome
Since the introduction of improved and aggressive therapy, the life expectancy of Marfan patients in the USA in 1996 was 61 years, with women generally living longer than men.
Dr AG Hall