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. Some Marfan features – for example, aortic enlargement (expansion of the main blood vessel that carries blood away from the heart to the rest of the body) – can be life-threatening.
The lungs, skin and nervous system may also be affected. Marfan syndrome does not affect intelligence.
Who has Marfan syndrome?
About 1 in 5,000 people have Marfan syndrome, including men and women of all races and ethnic groups. About 3 out of 4 people with Marfan syndrome inherit it, meaning they get the genetic mutation from a parent who has it.
But some people with Marfan syndrome are the first in their family to have it; when this happens it is called a spontaneous mutation.
There is a 50 percent chance that a person with Marfan syndrome will pass along the genetic mutation each time they have a child.
What are the symptoms of Marfan syndrome?
Marfan syndrome affects different people in different ways. Some people have only mild symptoms, while others are more severely affected. In most cases, the symptoms progress as the person ages.
The body systems most often affected by Marfan syndrome are:
Skeleton. People with Marfan syndrome are typically very tall, slender, and loose-jointed.
Because Marfan syndrome affects the long bones of the skeleton, a person’s arms, legs, fingers, and toes may be disproportionately long in relation to the rest of the body.
A person with Marfan syndrome often has a long, narrow face, and the roof of the mouth may be arched, causing the teeth to be crowded.
Other skeletal problems include a sternum (breastbone) that is either protruding or indented, curvature of the spine (scoliosis), and flat feet.
Eyes. More than half of all people with Marfan syndrome experience dislocation of one or both lenses of the eye. The lens may be slightly higher or lower than normal, and may be shifted off to one side. The dislocation may be minimal, or it may be pronounced and obvious.
One serious complication that may occur with this disorder is retinal detachment. Many people with Marfan syndrome are also nearsighted (myopic), and some can develop early glaucoma (high pressure within the eye) or cataracts (the eye’s lens loses its clearness).
Heart and blood vessels (cardiovascular system). Most people with Marfan syndrome have problems associated with the heart and blood vessels.
Because of faulty connective tissue, the wall of the aorta (the large artery that carries blood from the heart to the rest of the body) may be weakened and stretch, a process called aortic dilatation.
Aortic dilatation increases the risk that the aorta will tear (aortic dissection) or rupture, causing serious heart problems or sometimes sudden death.
Sometimes, defects in heart valves can also cause problems. In some cases, certain valves may leak, creating a “heart murmur,” which a doctor can hear with a stethoscope.
Small leaks may not result in any symptoms, but larger ones may cause shortness of breath, fatigue, and palpitations (a very fast or irregular heart rate).
Nervous system. The brain and spinal cord are surrounded by fluid contained by a membrane called the dura, which is composed of connective tissue.
As someone with Marfan syndrome gets older, the dura often weakens and stretches, then begins to weigh on the vertebrae in the lower spine and wear away the bone surrounding the spinal cord.
This is called dural ectasia. These changes may cause only mild discomfort; or they may lead to radiated pain in the abdomen; or to pain, numbness, or weakness in the legs.
Skin. Many people with Marfan syndrome develop stretch marks on their skin, even without any weight change.
These stretch marks can occur at any age and pose no health risk. However, people with Marfan syndrome are also at increased risk for developing an abdominal or inguinal hernia, in which a bulge develops that contains part of the intestines.
Lungs. Although connective tissue problems make the tiny air sacs within the lungs less elastic, people with Marfan syndrome generally do not experience noticeable problems with their lungs.
If, however, these tiny air sacs become stretched or swollen, the risk of lung collapse may increase.
Rarely, people with Marfan syndrome may have sleep-related breathing disorders such as snoring, or sleep apnea (which is characterized by brief periods when breathing stops).
Knowing the signs of Marfan syndrome can save lives
People with Marfan syndrome are born with it, but features of the disorder are not always present right away.
Some people have a lot of Marfan features at birth or as young children – including serious conditions like aortic enlargement.
Others have fewer features when they are young and don’t develop aortic enlargement or other signs of Marfan syndrome until they are adults. Some features of Marfan syndrome, like those affecting the heart and blood vessels, bones or joints, can get worse over time.
This makes it very important for people with Marfan syndrome and related disorders to receive accurate, early diagnosis and treatment.
Without it, they can be at risk for potentially life-threatening complications. The earlier some treatments are started, the better the outcomes are likely to be.
Knowing the signs of Marfan syndrome can save lives. Our community of experts estimates that nearly half the people who have Marfan syndrome don’t know it. This is something we are working hard to change.
What causes Marfan syndrome?
Marfan syndrome is caused by a defect, or mutation, in the gene that determines the structure of fibrillin-1, a protein that is an important part of connective tissue.
A person with Marfan syndrome is born with the disorder, even though it may not be diagnosed until later in life.
The defective gene that causes Marfan syndrome can be inherited: The child of a person who has Marfan syndrome has a 50 percent chance of inheriting the disease.
Sometimes a new gene defect occurs during the formation of sperm or egg cells, making it possible for two parents without the disease to have a child with the disease.
But this is rare. Two unaffected parents have only a 1 in 10,000 chance of having a child with Marfan syndrome.
Possibly 25 percent of cases are due to a spontaneous mutation at the time of conception.
Although everyone with Marfan syndrome has a defect in the same gene, different mutations are found in different families, and not everyone experiences the same characteristics to the same degree.
In other words, the defective gene expresses itself in different ways in different people. This phenomena is known as variable expression.
Scientists do not yet understand why variable expression occurs in people with Marfan syndrome.
How Marfan syndrome diagnosed?
There is no specific laboratory test, such as a blood test or skin biopsy, to diagnose Marfan syndrome. The doctor and/or geneticist (a doctor with special knowledge about inherited diseases) relies on observation and a complete medical history, including:
Information about any family members who may have the disorder or who had an early, unexplained, heart-related death.
A thorough physical examination, including an evaluation of the skeletal frame for the ratio of arm/leg size to trunk size.
An eye examination, including a “slit lamp” evaluation.
Heart tests such as an echocardiogram (a test that uses ultrasound waves to examine the heart and aorta).
The doctor may diagnose Marfan syndrome if the patient has a family history of the disease, and if there are specific problems in at least two of the body systems known to be affected.
For a patient with no family history of the disease, at least three body systems must be affected before a diagnosis is made. Moreover, two of the systems must show clear signs that are relatively specific for Marfan syndrome.
In some cases, a genetic analysis may be useful in making a diagnosis of Marfan syndrome, but such analyses are often time consuming and may not provide any additional helpful information.
Family members of a person diagnosed with Marfan syndrome should not assume they are not affected if there is no knowledge that the disorder existed in previous generations of the family.
After a clinical diagnosis of a family member, a genetic study might identify the specific mutation for which a test can be performed to determine if other family members are affected.
Recently, doctors discovered a connective tissue disorder known as Loeys-Dietz syndrome, which has several characteristics that overlap with those of Marfan syndrome.
When making a diagnosis, it is important to distinguish between the two disorders: Loeys-Dietz is more likely to cause fatal aortic aneurysms, and treatment for the two is different.
A diagnostic test for Loeys-Dietz syndrome is available.