MARFAN’S SYNDROME REPORT

Marfan syndrome is a genetic disorder that affects the body’s connective tissue. Connective tissue holds all
the body’s cells, organs and tissue together. It also plays an important role in helping the body grow and
develop properly.

Connective tissue is made up of proteins. The protein that plays a role in Marfan syndrome is called fibrillin-
1. Marfan syndrome is caused by a defect (or mutation) in the gene that tells the body how to make fibrillin-
1. This mutation results in an increase in a protein called transforming growth factor beta, or TGF-β. The
increase in TGF-β causes problems in connective tissues throughout the body, which in turn creates the
features and medical problems associated with Marfan syndrome and some related disorders.

Because connective tissue is found throughout the body, Marfan syndrome can affect many different parts of
the body, as well. Features of the disorder are most often found in the heart, blood vessels, bones, joints, and
eyes.

Marfan syndrome is inherited as an autosomal dominant condition.

What is autosomal dominant inheritance?

Autosomal dominant inheritance means that the gene in question is located on one of the autosomes. These
are numbered pairs of chromosomes, 1 through 22. (These chromosomes do not determine an offspring's
gender.) Dominant means that only one gene from one parent is necessary to pass down a trait or a
disorder. When a parent has a dominant trait or disorder, there is a 50 percent chance that any child he or she
has will also inherit the trait or disorder:

Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a
particular disease. The abnormal gene can be inherited from either parent or can be the result of a new
mutation (gene change) in the affected individual. In approximately 25-30 percent of Marfan syndrome
cases, this mutation occurs as the result of a new mutation. The risk of passing the abnormal gene from
affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females.

GENETIC DEFECTS :

Marfan is an autosomal dominant disorder. About 75% of the time the condition is inherited from a parent
while 25% of the time it is a new mutation. It involves a mutation to the gene that makes fibrillin which
results in abnormal connective tissue.

The DNA contains genetic information about the structure of proteins in the human body. It is packed in
chromosomes inside the cell nucleus Mutations on chromosones 15, in the FBN1 gene, cause Marfan
syndrome. The FBN1 gene encodes fibrillin-1 a protein that determines the formation of elastic fibers and as
a result, the connective tissues. Due to low levels of fibrillin-1, transforming growth factor beta becomes
abnormally active
PATHOPHYSIOLOGY

Marfan syndrome is a connective-tissue disease inherited in an autosomal dominant manner and caused
mainly by mutations in the gene FBN1. This gene encodes fibrillin-1, a glycoprotein that is the main
constituent of the microfibrils of the extracellular matrix. Most mutations are unique and affect a single
amino acid of the protein.

Reduced or abnormal fibrillin-1 leads to tissue weakness, increased transforming growth factor beta
signaling, loss of cell-matrix interactions, and, finally, to the different phenotypic manifestations of Marfan
syndrome.

The heart and blood vessels (cardiovascular), skeletal, and eye (ocular) systems are most often affected. It
includes overgrowth of the long bones of the arms and legs, abnormal side-to-side curvature of the spine
(scoliosis), indentation or protrusion of the chest wall (pectus deformity), dislocation of the lenses of the
eyes (ectopia lentis), nearsightedness (myopia), widening (aneurysm) and tear (dissection) of the main artery
that carries blood away from the heart (aorta), floppiness of the mitral valve (mitral valve prolapse) and
backward flow of blood through the aortic and mitral valves (aortic and mitral regurgitation).

LABORATORY DIAGNOSIS:

No universal, specific diagnostic test exists for Marfan syndrome despite the identification of the causative
gene. A diagnosis is made based upon a detailed patient and family history, a thorough clinical evaluation,
and a variety of specialized tests performed to identify key findings associated with Marfan syndrome. The
diagnosis of patients with Marfan syndrome should be made according to Ghent criteria and requires a
comprehensive clinical assessment of multiple organ systems. Genetic testing can also be useful in the
diagnosis of selected cases.

Ghent Criteria

Because no single test can diagnose Marfan syndrome, doctors use a set of guidelines called Ghent criteria
to help diagnose the condition. The Ghent criteria are divided into major criteria and minor criteria.
Sometimes genetic testing is part of this evaluation.

Major criteria include traits that are common in people who have Marfan’s syndrome. Minor criteria include
traits that are common in many people. Doctors use a scoring system based on the number and type of Ghent
criteria present to diagnose Marfan’s syndrome.

Echocardiography

-is a painless test that uses sound waves to create pictures of your heart and blood vessels.This test shows the
size and shape of your heart and the diameter of your aorta or other blood vessels. (The aorta is the main
artery that carries oxygen-rich blood to your body.) Echo also shows how well your heart's chambers and
valves are working. For people who have Marfan’s syndrome, echo mainly is used to check the heart's
valves and aorta.
Magnetic Resonance Imaging and Computed Tomography Scans

Magnetic resonance imaging (MRI) is a test that uses radio waves and magnets to create detailed pictures of
your organs and tissues. Computed tomography (CT) uses an x-ray machine to take clear, detailed pictures
of your organs.

MRI and CT scans are used to check your heart valves and aorta. These scans also are used to check for
dural ectasia, a nervous system complication of Marfan syndrome.

Slit-Lamp Exam

For this test, an ophthalmologist will use a microscope with a light to check your eyes. A slit-lamp exam can
find out whether you have a dislocated lens, cataracts, or a detached retina.

Genetic Testing

In general, genetic testing involves blood tests to detect changes in genes. However, because many different
genetic changes can cause Marfan’s syndrome, no single blood test can diagnose the condition.

GENETIC ADVANCEMENT

Marfan syndrome has no cure. However, treatments can help delay or prevent complications, especially
when started early.

Marfan syndrome can affect many parts of your body, including your heart, bones and joints, eyes, nervous
system, and lungs. The type of treatment you receive will depend on your signs and symptoms. So the
treatment of Marfan syndrome is directed toward the specific symptoms that are apparent in each individual.

Heart Treatments

Aortic dilation, or aortic aneurysm, is the most common and serious heart problem linked to Marfan
syndrome. In this condition, the aorta—the main artery that carries oxygen-rich blood to your body—
stretches and grows weak.

Medicines are used to try to slow the rate of aortic dilation. Surgery is used to replace the dilated segment of
aorta before it tears. If you have Marfan syndrome, you'll need routine care and tests to check your heart
valves and aorta.

Medicines

Beta blockers are medicines that help your heart beat slower and with less force. These medicines may help
relieve strain on your aorta and slow the rate of aortic dilation.

Some people have side effects from beta blockers, such as tiredness and nausea (feeling sick to your
stomach). If side effects occur, your doctor may prescribe a calcium channel blocker or ACE inhibitor
instead of a beta blocker. Both medicines help relieve stress on the aorta.

Studies suggest that blocking a protein called TGF-beta may help prevent some of the effects of Marfan
syndrome. Research shows that the medicine losartan may block the protein in other conditions.

The National Heart, Lung, and Blood Institute currently is sponsoring a study comparing losartan to a beta
blocker in children and adults who have Marfan syndrome. The study's goal is to find out which medicine, if
either, is best at slowing the rate of aortic dilation.
Surgery

If your aorta stretches, it's more likely to tear (a condition called aortic dissection). To prevent this, your
doctor may recommend surgery to repair or replace part of your aorta.

Surgery may involve:

A composite valve graft. For this surgery, part of the aorta and the aortic valve are removed. The aorta is
replaced with a man-made tube called a graft. A man-made valve replaces the original valve. Aortic valve-
sparing surgery. If your aortic valve is working well, your doctor may recommend valve-sparing surgery.
For this surgery, your doctor replaces the enlarged part of your aorta with a graft. Your aortic valve is left in
place.

After aortic surgery, you may need medicines or followup tests. For example, after a composite valve graft,
your doctor will prescribe medicines called anticoagulants, or "blood thinners."

Blood thinners help prevent blood clots from forming on your man-made aortic valve. You'll need to take
these medicines for the rest of your life. If you've had valve-sparing surgery, you'll only need to take blood
thinners for a short time, as your doctor prescribes.
If you've had a composite valve graft, you're at increased risk for endocarditis (EN-do-kar-DI-tis). This is an
infection of the inner lining of your heart chambers and valves. Your doctor may recommend that you take
antibiotics before certain medical or dental procedures that increase your risk of endocarditis.
Your doctor also may advise you to continue taking beta blockers or other medicines after either type of
aortic surgery.
After surgery, you may have routine cardiac magnetic resonance imaging (MRI) or cardiac computed
tomography (CT) scans to check your aorta.
Cardiac MRI is a painless test that uses radio waves and magnets to created detailed pictures of your organs
and tissues. Cardiac CT is a painless test that uses an x-ray machine to take clear, detailed pictures of your
heart.

Bone and Joint Treatments

If you have scoliosis (a curved spine), your doctor may suggest a brace or other device to prevent the
condition from getting worse. Severe cases of scoliosis may require surgery.
Some people who have Marfan syndrome need surgery to repair a chest that sinks in or sticks out. surgery is
done to prevent the chest from pressing on the lungs and heart.

Eye Treatments
Marfan syndrome can lead to many eye problems, such as a dislocated lens, nearsightedness, early glaucoma
(high pressure in the fluid in the eyes), and cataracts (clouding of an eye's lens).
Glasses or contact lenses can help with some of these problems. Sometimes surgery is needed.

Nervous System Treatments

Marfan syndrome can lead to dural ectasia. In this condition, a substance called the dura (which covers the
fluid around your brain and spinal cord) stretches and grows weak. This can cause the bones of the spine to
wear away. Dural ectasia usually is treated with pain medicines.

Lung Treatments

Marfan syndrome may cause pneumothorax, or collapsed lung. In this condition, air or gas builds up in the
space between the lungs and the chest wall.
If the condition is minor, it may go away on its own. However, you may need to have a tube placed through
your skin and chest wall to remove