Marfan Syndrome hard to identify


By BRIAN SODOMA

VIEW ON HEALTH

Jonathan Larson was on the cusp of greatness, only to die the night before his hit musical, Rent, was to have its New York debut in 1996. It's a tragic story in many ways, but perhaps even more so since the 35 year-old playwright's life could have been saved with a proper diagnosis of a condition he never knew he had.

It was later revealed that Larson had Marfan Syndrome. The genetic disorder is found in approximately 50,000 Americans today, or one in 5,000 to 10,000 people, experts estimate. A week before his death, Larson complained about chest pain and was taken to the hospital. A diagnosis of the flu was given at that time.

Since that time the condition has received much more research attention and doctors are more aware of its symptoms and signs than ever. Now, with early diagnosis and successful treatments in place, Marfan Syndrome sufferers are enjoy normal and even longer lives.

WHAT IS MARFAN SYNDROME?

Named after the French pediatrician Antoine Marfan, who was the first to make note of its symptoms and signs in the late 1800's, Marfan Syndrome is a genetic disorder of the body's connective tissue. The compromised state of the body's connective tissue comes as a result of a mutation, or change, in the FBN1, or fibrillin, gene. Every human being has a pair of FBN1 genes, which help to create the elastic fibers needed for the body's connective tissue to function. Sometimes one or both genes may be mutated.

The elastic fibers created by fibrillin are found in abundance in three particular areas of the body: the aorta, ligaments and the ciliary zonules of the eye. There's no coincidence that symptomatically these are the three areas of the body that can be harmed by the disorder and have strong ties to appropriately diagnosing patients.

Marfan Syndrome is most often an inherited condition. Approximately 75 percent of the people diagnosed with it have a parent who has it. If a parent is affected, a child has a 50 percent risk of having it, not unlike comparing the likelihood of having a boy or girl baby, says Dr. Alan Braverman, director of the Marfan Syndrome Clinic at Washington University School of Medicine in St. Louis.

Braverman comes from a family of six children and his father had the disorder; only one of his siblings has Marfan Syndrome, he says.

"It's inherited if an autosomal dominant parent has it. They carry one copy of that gene and each child has a 50 percent chance of inheriting it," he says.

Dr. Ron Lacro is the director of the cardiovascular genetics clinic at Children's Hospital Boston and is an assistant professor of pediatrics at Harvard Medical School. Lacro says Marfan Syndrome "is not common but common enough" to warrant research from the medical community, especially with cases like Larson and an increasing number of athletes suddenly collapsing and dying in the past decade. In nearly all of those latter cases, Marfan is not the cause, but a related or other genetic disorder that could have similar disastrous outcomes could be a possibility.

"The clinical findings are such that it's potentially devastating enough to make it important," he adds.

SYMPTOMS, TRAITS

Diagnosing Marfan Syndrome can be difficult. Because of its "high degree of clinical variability," according to the National Institutes of Health, there are a variety of symptoms and traits that can result in diagnosis or misdiagnosis, experts say.

People with Marfan Syndrome tend to be unusually tall compared to other members of their family. Several skeletal traits that are very common in Marfan sufferers are: long arms that, when held straight out perpendicular to the trunk of the body, are more than 5 percent longer than a person's height; rib overgrowth creating a pushed in sternum (pectus excavatum) or pushed out sternum (pectus dolichostenomelia); and scoliosis as well long boney (arachnodactyly) fingers. Marfan patients also tend to be very flexible and many suffer from nearsightedness. Retinal detachment, or displacement of the lens from the eye's pupil is also a "hallmark feature" of someone with Marfan Syndrome, according to the NIH.

"There are suspensory ligaments that hold the lens of the eye in place. If those are lax, the lens will fall out of place," Braverman explains.

One can get a gene test for Marfan Syndrome, but it can produce false negatives and positives, Lacro says. The doctor adds that the three primary factors doctors look for are: enlargement of the aorta, dislocation of the ocular lens and the presence of the FB1 mutation.

"Many people may have these relatively minor findings like the skeletal symptoms and it brings people to raise the question 'Do I have Marfan Syndrome?' But the two most important tests that need to be done are the eye exam and the echocardiogram to make sure the aorta is a normal size," Lacro says.

When getting the heart checked, the doctor says three centimeters is the normal size for an aorta. Anything larger should be a red flag, and an aorta five centimeters or larger may require immediate surgery.

A stretched aorta should be easily seen in an echocardiogram, adds Braverman, who also said a systemic score looking at four factors, skeleton, eyes, arm length and flexibility, was put into place in 2010 to help diagnose patients.

Braverman also likes to discuss a family history of Marfan Syndrome with patients. Often times, patients don't know if a relative had the condition. But after talking through their family history and being reminded that a relative or two passed away rather young, patients begin to realize that family members may have had it without being diagnosed.

"Many times I'll ask 'Do your parents have Marfan Syndrome?' They'll say 'no.' But then I'll learn the patient's father died young and suddenly from a heart attack. Then they start putting it together. 'Oh yeah, my uncle died young too,' they'll say," Braverman adds.

MANAGEMENT, TREATMENT

Both doctors say that people curious about Marfan Syndrome evaluation may come to their office for a variety of reasons. Some may have read or seen reports in the media, while others may complain about chest pain and have a doctor notice some physical characteristics that seem in line with the condition. Lacro says, because of heightened awareness and curiosity, it is more common to be diagnosing children than adults these days.

"I'd say that if I have a hundred people coming in who are tall and lanky and have some symptoms, most will not have Marfan Syndrome. ... But it's good for people to know either way," Braverman adds.

The good news is that most of the people who are diagnosed with Marfan Syndrome today can likely lead long lives well into their 70s, says Braverman. But monitoring the condition is key.

Obviously, the greatest threat with Marfan Syndrome is to the heart. An aortic dissection, or tearing of the aorta, is a common cause of sudden death for undiagnosed Marfan Syndrome patients. With the aorta not having the means to be elastic and flexible, it runs the risk of tearing, Braverman explains.

A surgical solution known as a tube graft is a very low-risk procedure that has helped Marfan Syndrome patients lead normal lives since the 1960s. While it's not difficult to find a surgeon capable of doing the procedure, Braverman emphasizes that a specialist should be sought out who has plenty of experience with this specific procedure.

"It's not the same as a bypass surgery. ... Because there aren't as many cases of this, it's not the sort of things most surgeons do frequently. (But) Most major cities have the expertise," he says.

If a Marfan Syndrome patient has severe scoliosis, surgery may also be required. Both doctors say having regular check-ups with an orthopedist, cardiovascular specialist and ophthalmologist is key to leading a long, normal life with the disorder.

Some lung complications and neurological problems have been associated with Marfan Syndrome, but they are very rare.

In addition, the NIH makes other lifestyle suggestions for those suffering from Marfan Syndrome. The department says patients should avoid contact sports, competitive sports and isometric sports; although it is encouraged for Marfan sufferers to stay active with aerobic activity in general.

Those with the condition should also avoid activities that could injure joints; avoid agents or drugs that stimulate the cardiovascular system, such as the routine use of decongestants or caffeine, as they can aggravate an arrhythmia.

According to the NIH, Marfan patients should avoid LASIK correction for eye issues.

RESEARCH

Lacro is participating in a study funded by the NIH that is looking at the use of two blood-pressure-lowering drugs for helping to reduce the size of the aorta in patients with Marfan Syndrome. It is common once an aorta is diagnosed as being large for doctors to prescribe atenolol, a beta blocker, or blood pressure lowering drug, to help reduce the aorta's size. Depending on the results found after the drug is administered, doctors then evaluate whether to move forward with surgery or not.

But the study is looking at a second blood-pressure-lowering drug called Losartan that may offer better results, Lacro says. The 608-person study, with age ranges between 6 months and 25 years, has half its patients on one drug and half using the other. Results should be available in 2014.

The study was prompted after researchers found positive results in mice. Limited use in humans also indicated Losartan may be a better choice for reducing the size of the aorta.

"There's a lot of research being put into this aortic disease in general. Hopefully the outcomes will be much better in the future," he said.

For more information about Marfan Syndrome, visit: www.marfan.org.

 

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