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| DiseaseID |
HGD6 |
| Genetic
Disorder |
Marfan Syndrome
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| Gene
Name |
FBN1 gene(fibrillin-1) |
| Description |
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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| Symptoms |
Persons with Marfan syndrome are usually tall with long, thin arms and legs and spider-like fingers -- a condition called arachnodactyly. When they stretch out their arms, the lenght of their arms is significantly greater than their height.
Other symptoms include:
Highly arched palate and crowded teeth Nearsightedness Dislocation of the lens of the eye Funnel chest (pectus excavatum) or pigeon breast (pectus carinatum) Scoliosis Flat feet Learning disability Thin, narrow face Micrognathia (small lower jaw) Coloboma of iris Hypotonia
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| Causes |
Marfan syndrome is caused by defects in a gene called fibrillin-1. Fibrillin-1 plays an important role as the building blocks for elastic tissue in the body. A problem with this gene results in changes in elastic tissues, particularly in the aorta, eye, and skin. The gene defect also causes overgrowth of the long bones of the body. resulting in the tall height and long arms and legs seen in persons with this syndrome. How this overgrowth happens is not well understood.
In most cases, Marfan syndrome is inherited, which means it is passed down through families. However, up to 30% of cases have no family history. Such cases are called "sporadic." In sporadic cases, the syndrome is believed to result from a spontaneous new gene defect. |
| Diagnosis |
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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| Treatment |
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 mm in adults and older children, when the aortic diameter increases by 1.0 mm 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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