domingo, 6 de julio de 2014

Learning About Marfan Syndrome

Learning About Marfan Syndrome

Genome.gov National Human Genome Research Institute National Institutes of Health



What is Marfan syndrome?

Marfan syndrome is one of the most common inherited disorders of connective tissue. It is an autosomal dominant condition occurring once in every 10,000 to 20,000 individuals. There is a wide variability in clinical symptoms in Marfan syndrome with the most notable occurring in eye, skeleton, connective tissue and cardiovascular systems.
Marfan syndrome is caused by mutations in the FBN1 gene. FBN1 mutations are associated with a broad continuum of physical features ranging from isolated features of Marfan syndrome to a severe and rapidly progressive form in newborns.
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What are the symptoms of Marfan syndrome?

The most common symptom of Marfan syndrome is myopia (nearsightedness from the increased curve of the retina due to connective tissue changes in the globe of the eye). About 60 percent of individuals who have Marfan syndrome have lens displacement from the center of the pupil (ectopia lentis). Individuals who have Marfan syndrome also have an increased risk for retinal detachment, glaucoma and early cataract formation.
Other common symptoms of Marfan syndrome involve the skeleton and connective tissue systems. These include bone overgrowth and loose joints (joint laxity). Individuals who have Marfan syndrome have long thin arms and legs (dolichostenomelia). Overgrowth of the ribs can cause the chest bone (sternum) to bend inward (pectus excavatum or funnel chest) or push outward (pectus carinatum or pigeon breast). Curvature of the spine (scoliosis) is another common skeletal symptom that can be mild or severe and progressively worsen with age. Scoliosis shortens the trunk also contributes to the arms and legs appearing too long.
Cardiovascular malformations are the most life threatening symptom of Marfan syndrome. They include dilated aorta just as it leaves the heart (at the level of the sinuses of Valsalva), mitral valve prolapse, tricuspid valve prolapse, enlargement of the proximal pulmonary artery, and a high risk for aortic tear and rupture(aortic dissection).
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How is Marfan syndrome diagnosed?

The diagnosis of Marfan syndrome is a clinical diagnosis that is based on family history and the presence of characteristic clinical findings in ocular, skeletal and cardiovascular systems. There are four major clinical diagnostic features:
  1. Dilatation or dissection of the aorta at the level of the sinuses of Valsava.
  2. Ectopia lentis (dislocated lens of the eye).
  3. Lumbosacral dural ectasia determined by CT scan or magnetic resonance imaging (MRI).
  4. Four of the eight typical skeletal features.
Major criteria for establishing the diagnosis in a family member also include having a parent, child, or sibling who meets major criteria independently, the presence of an FBN-1 mutation known to cause the syndrome, or a haplotype around FBN-1 inherited by descent and identified in a familial Marfan patient(also known as genetic linkage to the gene).
The FBN1 gene is the gene associated with the true Marfan syndrome. Genetic testing of the FBN1 gene identifies 70 - 93 percent of the mutations and is available in clinical laboratories. However patients negative for the test for gene mutation should be considered for evaluation for other conditions that have similar features of Marfan syndrome such as Dietz syndrome, Ehlers Danlos syndrome, and homocystinura. To unequivocally establish the diagnosis in the absence of a family history requires a major manifestation from two systems and involvement of a third system. If a mutation known to cause Marfan syndrome is identified, the diagnosis requires one major criterion and involvement of a second organ system.
To establish the diagnosis in a relative of a patient known to have Marfan Syndrome (index case) requires the presence of a major criterion in the family history and one major criterion in an organ system with involvement of a second organ system.
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What is the treatment for Marfan syndrome?

Individuals who have Marfan syndrome are treated by a multidisciplinary medical team that includes a geneticist, cardiologist, ophthalmologist, orthopedist and cardiothoracic surgeon.
Eye problems are generally treated with eyeglasses. When lens dislocation interferes with vision or causes glaucoma, surgery can be performed and an artificial lens implanted.
Skeletal problems such as scoliosis and pectus excavatum may require surgery. For those individuals who have pes planus (flat feet) arch supports and orthotics can be used to decrease leg fatigue and muscle cramps.
Medication, such as beta blockers, is used to decrease the stress on the aorta at the time of diagnosis or when there is progressive aortic dilatation. Surgery to repair the aorta is done when the aortic diameter is greater than 5 cm in adults and older children, when the aortic diameter increases by 1.0 cm per year, or when there is progressive aortic regurgitation.
Cardiovascular surveillance includes yearly echocardiograms to monitor the status of the aorta. Currently the use of beta blocker medications has delayed but not prevented the need to eventually perform aortic surgery.
Recent work on Angiotensin II receptor blockers, another blood pressure medication like beta blockers, has shown additional promise to protect the aorta from dilatation. Clinical trials will be starting soon to see if this drug can prevent the need for surgery better than beta blockers have.
Individuals who have Marfan syndrome are advised to avoid contact and competitive sports and isometric exercise like weight lifting and other static forms of exercise. They can participate in aerobic exercises like swimming. They are also advised to avoid medications such as decongestants and foods that contain caffeine which can lead to chronic increases in blood pressure and stretch the connective tissue in the cardiovascular system.
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Is Marfan syndrome inherited?

Marfan syndrome is inherited in families in an autosomal dominant manner. Approximately seventy-five percent of individuals who have Marfan syndrome have a parent who also has the condition (inherited). Approximately 25 percent of individuals who have Marfan syndrome, have the condition as a result of a new (de novo) mutation. When a parent has Marfan syndrome, each of his or her children has a 50 percent chance (1 chance in 2) to inherit the FBN1 gene. While Marfan syndrome is not always inherited, it is always heritable.
When a child with Marfan syndrome is born to parents who do not show features of the Marfan syndrome, it is likely the child has a new mutation. In this family situation, the chance for future siblings (brothers and sisters of the child with Marfan syndrome) to be born with Marfan syndrome is less than 50 percent. But the risk is still greater than the general population risk of 1 in 10,000. The risk is higher for siblings because there are rare families where a Marfan gene mutation is in some percentage of the germline cells of one of the parents (testes or ovaries).
Prenatal testing for Marfan syndrome is available when the gene mutation is known, and also using a technique called linkage analysis (tracking the gene for Marfan syndrome in a family using genetic markers).
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Clinical Research on Marfan syndrome

Currently, NHGRI is not conducting research on Marfan syndrome.
The National Institutes of Health is conducting a research study involving Marfan syndrome:
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Additional Resources For Marfan Syndrome

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