What are the other Names for this Condition? (Also known as/Synonyms)

• Marfan’s Syndrome
• MFS (Marfan Syndrome)

What is Marfan Syndrome? (Definition/Background Information)

• Marfan Syndrome (MFS) is an inherited disorder that affects the connective tissue. The disorder affects the skeletal system (bones), cardiovascular system (heart and blood vessels), eye, skin, lungs, and the dural sac (membranous sac surrounding the spinal cord)
• The connective tissues are made up of cells, extra-cellular matrix and fibers that are responsible for maintaining a structural framework within the body, by connecting tissue and protecting organs
• In nearly three-fourths of the individuals with Marfan Syndrome, the inherited form is observed. Thus, a family history of MFS is a major risk factor. In the remaining one-fourth, the disorder develops spontaneously; the risk factors are generally not known in such cases
• Marfan Syndrome is caused by a mutation in the FBN1 gene. It is inherited in an autosomal dominant manner. In this type of inheritance, a single copy of the defective gene in every cell of the body is sufficient for manifestation of MFS. An affected individual inherits the condition from an affected parent
• The two characteristic features of Marfan Syndrome that are observed are vision abnormalities (such as severe short-sightedness, early-onset cataracts, and glaucoma) and abnormalities in the aorta (artery that pumps blood from heart to the rest of the body)
• Individuals with Marfan Syndrome may also present symptoms such as tall and thin body appearance, long arms and legs, long fingers, curved spine, narrow face, and crowded teeth, among others
• In some, the potential complications include rupture of aorta, sudden collapse of the lungs, mitral wall prolapse (causing heart murmurs), susceptibility to infection in the inner wall of heart after surgeries, and increased (heart) stress in pregnant women
• Marfan Syndrome may be diagnosed on the basis of a physical examination, assessment of symptoms, evaluation of personal and family medical history, vision tests, echocardiogram (ECG), and molecular genetic test for checking/confirming the mutation in FBN1 gene
• The treatment for Marfan Syndrome is symptomatic. The treatment options include medications for cardiac abnormalities, surgery to repair skeletal abnormalities, straightening of teeth, and visual aids or surgery to improve one’s vision
• With timely diagnosis, individuals with Marfan Syndrome may be able to adopt a lifestyle reducing risk for cardiovascular events by addressing symptoms in a timely fashion improving both the quality of life and one’s life-span

Who gets Marfan Syndrome? (Age and Sex Distribution)

• Marfan Syndrome occurs at a reported frequency of 2-3 per 10,000 individuals
• The age of onset of symptom can vary widely. In some cases, MFS may be observed at birth; whereas in others, symptom manifestation may begin during teenage or adulthood, or it may progress slowly over time
• Equal occurrence in both males and females are observed
• The disorder is reported worldwide; no specific ethnic or racial predilection is observed

What are the Risk Factors for Marfan Syndrome? (Predisposing Factors)

• Marfan Syndrome is a genetically-inherited disorder, and therefore, having a family history of the condition is a major risk factor
• In nearly 30% of the cases, MFS occurs sporadically; the risk factors in such individuals is not clearly known

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Marfan Syndrome? (Etiology)

Marfan Syndrome is inherited in an autosomal dominant manner. It is caused by a mutation in the FBN1 gene.

• This gene codes for the fibrillin-1 protein. Under normal circumstances, the fibrillin-1 protein interacts with other similar molecules to form microfibrils (thread-like structures)
• The microfibrils strengthen the connective tissue, offer flexibiltiy, as well as bind growth factors. The growth factors are released in times of need, such as during growth, maintenance, and repair of tissues and organs
• A mutated FBN1 gene may lead to a decreased or dysfunctional fibrillin-1 protein
• This results in a compromised microfibril formation and a consequential loss of elasticity in the connective tissue
• This also results in increased levels of growth factors, such as the transforming growth factor beta-1 (TGFβ-1). TGFβ-1 is involved in a number of cellular processes including growth and differentiation of cell
• The combination of the above effects result in overgrowth of long bones and affects the lungs, aorta, eyes, skin and the spinal cord. Also, an increase in the levels of TGFβ-1 is known to affect the elasticity of aorta
• In 70-75% of affected individuals, the condition is inherited in an autosomal dominant manner. In this type of inheritance, a single defective copy of the causative gene in every cell of an affected individual’s body is sufficient to cause MFS. An affected individual inherits the condition from an affected parent. The likelihood of an individual with the condition passing the defective gene to the next generation is 50%
• In 25-30% of the affected population, Marfan Syndrome develops due to spontaneous mutation(s) in the FBN1 gene. In such cases, the cause of mutations is not known

What are the Signs and Symptoms of Marfan Syndrome?

The following are signs and symptoms associated with Marfan Syndrome:

• The individuals are generally taller than other members of the family
• They may have disproportionately long and  thin arms and legs; thin, long (spider-like) fingers
• Sunken chest bone, which can cause heart and lung problems. Or, a chest that projects outwardly
• Flatfeet
• Severe myopia or near-sightedness
• Early-onset cataract (cloudy eye lens)
• Glaucoma: Increased pressure in the eye, specifically on the eyeball may cause defect in the nerve that carries information from the eye to the brain
• Flexible joints
• Eye lens might dislocate
• Narrow face
• Small lower jaw, crowding of teeth
• Curve in the spine
• Heart valve defects

Note: The age of onset and severity of symptoms may vary widely among the affected individuals.

How is Marfan Syndrome Diagnosed?

The diagnosis of Marfan Syndrome may be made through the following tests and exams:

• A complete physical examination with assessment of symptoms
• Evaluation of one’s personal and family medical history
• Vision tests and eye exams
• Dental exams
• Echocardiogram to check and monitor heart function
• Imaging studies, such as X-ray, to understand skeletal abnormalities
• Computed tomography (CT) scans and/or magnetic resonance imaging (MRI) of the affected region, to check for structural changes to organs and body systems
• Molecular genetic testing to confirm FBN1 gene mutation

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Marfan Syndrome?

Some potential complications associated with Marfan Syndrome include:

• Bacterial endocarditis (inflammation of the inner wall of the heart due to a bacterial infection) after a surgery is also a common complication  
• Dislocation of eye lens
• Vision loss
• Spontaneous pneumothorax (sudden collapse of the lung)  
• Increased stress on the heart, especially in pregnant women
• Sudden aortic rupture that may be fatal
• Mitral wall prolapse can cause a regurgitation of blood within the heart; this can also be fatal

How is Marfan Syndrome Treated?

The treatment of Marfan Syndrome is symptomatic and supportive, since the disorder has a genetic basis and cannot be cured. The treatment options may include:

• Prescription of vision aids to improve vision
• Medication to slow heart rate, if needed, and to reduce the chance of an aortic rupture
• Bracing to manage scoliosis
• Surgery to repair the aortic root and mitral valve  
• Surgery to repair skeletal abnormalities such as sunken chest bone and scoliosis
• Surgery to remove cataracts, repair eye abnormalities
• Antibiotics to avoid bacterial endocarditis, which may be recommended after dental procedures and surgeries

Routine and regular monitoring of vision, heart function, and skeletal deformities is essential and highly recommended.

How can Marfan Syndrome be Prevented?

Marfan Syndrome is a genetic disorder, and presently there are no guidelines or methods available for its prevention.

• Avoiding strenuous activity (including intense sporting activities) can help individuals with the syndrome minimise the risk for medical emergencies such as aortic rupture
• Genetic counseling of prospective parents with a family history of MFS may help them understand the risks during child planning
• It is important to maintain period visits to the healthcare provider to monitor one’s vision, heart condition and skeletal abnormalities

What is the Prognosis of Marfan Syndrome? (Outcomes/Resolutions)

The prognosis of Marfan Syndrome is considered to be good, in terms of quality of life and lifespan, if

• The disorder is diagnosed early, treated promptly, and monitored regularly
• Necessary changes to lifestyle are made, such as reducing risk for adverse cardiovascular events (avoiding stress on the heart by not engaging in strenuous physical activities), and undertaking regular screening for eye and bone health

Additional and Relevant Useful Information for Marfan Syndrome:

According to Wikipedia, Abraham Lincoln was once thought to have Marfan Syndrome; but, this has been contested and considered to be unlikely by modern geneticists. Conclusive confirmation through DNA testing is not possible, as access to Lincoln's DNA was denied.