What is Marfan syndrome?
How is it inherited?
What symptoms are involved?
How common is it?
What causes Marfan syndrome?
How is Marfan syndrome diagnosed?
Is diagnostic testing available?
What treatments are available for Marfan syndrome?
Resources

What is Marfan syndrome?

Marfan syndrome is an inherited disorder that affects primarily the eyes, the heart, blood vessels (cardiovascular systems), and the bones and joints (skeletal system). The disorder was first described by a French pediatrician, Antoine Marfan in 1896 and bears his name.
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How is it inherited?

Marfan syndrome is inherited in an autosomal dominant manner. If a person is affected with Marfan syndrome, they face a 50% chance of passing on the disease with every pregnancy. In 1 in 4 of all cases of Marfan syndrome, the parents are not affected. In these cases, the condition arises in the affected person because of a spontaneous or new mutation in the egg or the sperm of one of the parents. The disorder is fully penetrant, meaning that unaffected relatives of a Marfan patient will not pass the disorder on to their children.
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What symptoms are involved?

People with Marfan syndrome tend to have the following skeletal features:

• tall and thin stature with long extremities
  
• chest wall deformities (termed pectus excavatum or pectus carinatum)
  
• flat feet (pes planus)
  
• curvature of the spine (scoliosis)
  
• loose joints.
  
• The face tends to be long and narrow (keeping with the generalbody shape)
  
• problems with their heart and blood vessels.

The most serious cardiovascular problem is progressive dilatation or enlargement of the aorta at the point where it comes off the heart (aortic root) called an aortic aneurysm. This occurs because the aorta is weakened due to the disorder. People affected with Marfan syndrome usually have an aortic root that tends to enlarge with time and when the aorta reaches a certain size it can rupture or dissect. Dissection occurs when the blood enters the wall of the aorta. If either of these events occurs, the affected individual can die suddenly. The size of the aorta can be measured using echocardiography, a painless and non-invasive test that uses sound waves to visualize the heart and aorta. When the aortic root reaches 5 cm or greater in size, it is recommended that patients undergo surgical repair of the enlarged aorta. This procedure has increased the life expectancy of individuals with Marfan syndrome. People with Marfan syndrome also tend to have problems with the mitral valve in the heart. This can be an abnormal motion of the valve called mitral valve prolapse, or it can be an abnormal functioning of the valve called mitral valve regurgitation, or both. This defect can also be surgically repaired

 

Non life-threatening, but still of concern, are the eye complications associated with the syndrome. These include myopia (nearsighted), lens dislocation, and retinal detachment. Myopia is a common eye problem for many people with and without Marfan syndrome. Lens dislocation, on the other hand, is a hallmark of the disease it occurs in relatively few other syndromes. It is found in roughly half of patients with Marfan syndrome.

 

Other systems which are also involved in patients with Marfan syndrome include the lungs, skin, and the nervous system. Lung complication involves spontaneous rupture of lung tissue (pneumothorax). Stretch marks occur particularly over the shoulder, back, and thighs. Hernias in the groin area (inguinal hernias), umbilical, diaphragmatic, and incisional are also common features of this condition. Lastly, the nervous system involvement includes widening of the spinal canal (dural extasia) in the lower back and dilated cisterna magna.
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How common is it?

Marfan syndrome affects approximately 1 in 10,000 individuals in the United States. It affects men, women, and all racial and ethnic groups equally.
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What causes Marfan syndrome?

Mutations in the FBN1, located in the long arm of chromosome 15, are responsible for Marfan syndrome. FBN1 encodes fibrillin-1 a connective tissue protein that contributes to large structures called microfibrils. Microfibrils are found in most connective tissues.

 

The mutant forms of fibrillin-1 have dominant-negative activity. This means that the mutant forms can interfere with the function of the normal protein derived from the normal gene. This is a hallmark feature of Marfan syndrome and results in a severe reduction of microfibrils in tissues in the matrix deposited by cultured dermal fibroblasts. The residual level of protein is generally far below the 50% level predicted by the presence of a wild-type copy of FBN1 in all the affected individuals.
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How is Marfan syndrome diagnosed?

The diagnosis of Marfan syndrome is a clinical diagnosis based upon family history and a constelation of findings including the ocular, cardiovascular, and skeletal manifestations as described above. If an individual has a first-degree relative affected, they should manifest features in two systems before they are classified as affected. If an individual has no first-degree relative affected, they need to show the distinctive skeletal features and have at least two other systems involved. The diagnosis is generally made by a geneticist or cardiologist.

 

Because so many of the features of Marfan syndrome are found in the general population, to be considered affected individuals must show at least one major manifestation: lens dislocation, aortic root dissection or dilation, or widening of the spinal cord (dural ectasia). When people are diagnosed with Marfan syndrome based solely on physical appearance, they may not have the syndrome.

 

Included in the differential diagnosis for Marfan syndrome are homocystinuria, familial mitral valve prolapse syndrome, familial annuloaortic ectasia, familial thoracic aortic aneurysm, congenital contractural arachnodactyly (Beals syndrome), Ehlers-Danlos syndrome and Stickler syndrome.
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Is diagnostic testing available?

Molecular genetic testing of the FBN1 gene consists of linkage analysis and mutational screening, these test are best used to determine whether an individual is predisposed to develop Marfan syndrome that is already present in a family member. Neither tests, by itself, can establish or exclude the diagnosis of Marfan syndrome.

 

Linkage analysis can determine whether an individual had inherited a mutant FBN1 gene that is associated with disease in their family. It can only be considered in families with multiple affected family members who are willing to participate in the analysis. The markers used for Marfan syndrome linkage are highly informative, and can be used in nearly all of the families.

 

Direct mutational screening for FBN1 mutations is cumbersome due to the large size of the gene and that almost every family or person has a unique mutation. The wide distribution of mutations without any mutant alleles that are common in specified populations. Without a definitive correlation between physical manifestation and genetic status, identification of a mutation has little prognostic value and has not been proven to reliably guide patient management. Pre-symptomatic or prenatal diagnosis is possible in selected families in whom disease-causing mutations have previously been identified. Mutation screening is available on a research basis only.

 

Immunohistochemical and biochemical analysis of the fibrillin-1 protein expressed from cultured skin fibroblasts can detect abnormalities in most samples from patients with Marfan syndrome. This is currently available on a research basis only.
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What treatments are available for Marfan syndrome?

Because it is difficult to predict the severity of cardiovascular problems in individuals with Marfan syndrome, it recommended that affected individuals have echocardiograms done at least once a year. As the aorta dilates or if the valvular problems progress, these evaluations must be carried out more frequently. Beta-blocker therapy (medication to decrease rate and strength the heart beats) is used to treat patients with Marfan syndrome.

 

If the aortic root size reaches 5cm or more then it is recommended that patients undergo surgical repair of the enlarged aorta. Severe mitral valve prolapse and abnormal blood flow can also be surgically repaired. Likewise, many of the skeletal features can be surgically corrected, such as severe scoliosis and pectus deformities

 

Lens dislocation usually does not require surgical intervention unless the lens displaces obstructs the line of vision. Retinal detachment is rare, but a serious problems and can cause loss of sight. Because of the ocular complications, we recommend that patients with Marfan syndrome schedule eye exams on a yearly basis.
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Resources

• National Marfan syndrome Foundation
• Gene Tests
• Research References
• OMIM

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