Marfan syndrome is an inherited condition that affects the strength of connective tissues in the body. These tissues provide the framework that holds the body together and play an important role in growth and development. Because connective tissue is found throughout the body, patients with Marfan syndrome have problems with a number of systems including bones, joints, eyes, heart, blood vessels, nervous system, skin, and lungs.
Marfan syndrome affects both sexes and all ethnic groups. However, it is relatively rare. About 1 in 5000 people are born with the disorder and an estimated 200,000 individuals in the United States are currently diagnosed with it.
It is caused by a genetic mutation that creates problems in a protein called fibrillin-1. Fibrillin-1 is an essential component of connective tissue. The gene is called FBN1. Three out of every four people with Marfan syndrome inherit the disorder from a parent with the disease. One out of four have a spontaneous mutation in the gene meaning that neither parent has Marfan syndrome.
It is an autosomal dominant condition. This type of inheritance means each new child of an affected parent has a fifty percent chance of inheriting the disease. Spontaneous mutations in FBN1 account for approximately twenty-five percent of cases. The likelihood of such a mutation is quite uncommon, occurring in about 1 of 20,000 births.
The diagnosis of Marfan syndrome remains a clinical one. There is a wide range of variability in the manifestations of the disease within and among families. Also, many individuals without the syndrome have one or more clinical features that may suggest that they may have Marfan syndrome and can be the reason for referral for work-up for the Marfan syndrome. Such common features include tall and thin stature, heart murmurs or eye problems. A person is diagnosed with Marfan syndrome when they have a number of the clinical signs of this disease.
There is genetic testing for the mutation in the fibrillin-1 gene. The results of the testing are not always straightforward. If a person undergoes genetic testing, he or she would work with a genetic counselor to explain the results.
Most people with Marfan syndrome suffer from near-sightedness (axial and lenticular myopia) and visual distortion (astigmatism). Other signs and symptoms include ectopia lentis, corneal thinning, flattened corneal curvature, cataracts, glaucoma, strabismus, and retinal detachment.
Ectopia lentis is a shift in the location of the lens inside the eye. The lens moves from its centered location in the eye so that the person is not looking through the center of their lens. This dislocation is caused by weakness in the connective tissue that holds the lens in place (zonules). Ectopia lentis occurs in roughly sixty-percent of individuals with Marfan syndrome and is one of the major criteria for the clinical diagnosis of this condition [See figures 1 and 2]. If a person does not have dislocated lenses, it does not mean that they do not have Marfan syndrome.
Many of the symptoms of Marfan syndrome are striking, but the most serious problems associated with the Marfan syndrome involve the heart and blood vessels. There can be problems with one of the valves in the heart called the mitral valve. The valve leaflets are too large and can bow in the wrong direction. This is called mitral valve prolapse. In individuals with mitral valve prolapse, the mitral valve makes a click as it moves backward. This sound that can be detected with a stethoscope when a doctor listens to the heart. In about one-third of people with prolapse blood leaks backward through the valve (mitral valve regurgitation) producing a heart murmur that can also be heard through a stethoscope. A few individuals with mitral regurgitation develop symptoms like breathlessness, an irregular pulse (palpitations), or extreme tiredness.
A second problem can occur with the aorta (the major blood vessel coming off of the heart). Some enlargement of the aortic root is found in nearly everyone with Marfan syndrome. A substantial (about two inches) dilatation of the aorta (aneurysm) can result in two things: an abnormal back-flow of blood into the heart (aortic regurgitation) or a tear in the middle layer of the aorta (dissection). Dissecting aortic aneurysms are the most frequent cause of death in persons with Marfan syndrome.
Most patients are evaluated for Marfan syndrome because of their skeletal manifestations. A person with the disorder will usually be tall, thin, and loose-jointed. Frequent signs of the disease include long, slender fingers and toes (arachnodactyly) and flat arches (pes planus). Curvature of the spine (scoliosis and kyphosis) and protrusion or indentations of the breastbone (pectus carinatum and excavatum) are also common problems. The roof of the mouth (palate) may be highly arched, causing dental crowding, and the face may seem narrow and elongated. Persons with Marfan syndrome may also demonstrate an arm-span-to-height ratio greater than 1.05.
Striae are bands of thin wrinkled skin, initially red but becoming purple and white, which tend to appear in areas prone to stress, such as the shoulders, hips, and lower back.
Decreased flexibility in the air sacs of the lungs can be detected in nearly everybody with the disease, but does not pose any serious problem. One out of twenty people diagnosed with the condition experience the feeling of breathlessness or chest pain as a direct result of the spontaneous collapse of the lung (spontaneous pneumothorax). Some people with Marfan syndrome also suffer from sleep-disordered breathing.
There is no cure for Marfan syndrome at this time. But with early detection and awareness, we can improve the quality of life and life expectancy of a person with Marfan’s syndrome.
Individuals with Marfan syndrome can develop severe orthopedic, cardiovascular, and ocular challenges, but medical and surgical advancements have increased the life span of people with Marfan syndrome dramatically over the last two decades. In 1972 the average life expectancy was about forty-five years, now the average life expectancy is about seventy years.
• Annual echocardiogram to monitor the heart • Initial careful slit-lamp eye examination, with regular follow-up • Careful monitoring of the skeletal system • Lifestyle adjustments: avoidance of strenuous activity and contact sports
The use of beta-blocker agents, medications used to prevent progressive enlargement of the aorta and treat high blood pressure, have become an essential aspect of cardiovascular management. Individuals with Marfan syndrome are advised to refrain from heavy lifting and forceful activity. In the case of aortic regurgitation or significant dilation of the aortic root, surgical repair may become necessary.
A back brace is often recommended for children with moderate scoliosis (between 20º and 40º). If the curve becomes severe (more than 40º), surgery is usually considered to prevent further complications. The sole treatment for pectus excavatum or carinatum is surgery. Management for pes planus is not ordinarily required, but special cushions, inserts, or orthotics may help. Wearing comfortable shoes is also recommended.
Comprehensive ophthalmologic care is necessary to achieve the best possible vision in people with Marfan syndrome. Patients with subluxated lenses are treated with glasses or contact lenses whenever possible. If the visual acuity can not be improved with glasses, surgery may be necessary to optimize vision. Individuals with cataracts require lens extraction with or without placement of an intraocular lens. Glaucoma may require treatment with medications or surgery. If there is a retinal detachment, surgery will be required to fix the problem.
Removal of clear, dislocated lenses in children remains a difficult decision to make. There is a general consensus that they should be removed if they are interfering significantly with vision by causing large degrees of astigmatism that cannot be corrected with glasses or contact lenses. Lens extraction in children with Marfan syndrome does have an increased risk of complications such as retinal detachment.
Please visit the National Marfan Foundation website. A large number of frequently asked questions have been answered by experts in the field under the heading of “living with Marfan syndrome”.
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