Syndrome Synopsis: Marfan Syndrome
by Beth A. Pletcher, MD, February 1999

For many clinicians a "marfanoid habitus" represents the hallmark for Marfan syndrome and usually will prompt medical evaluation. However, over the years I have had the opportunity to see many individuals with Marfan syndrome and have had a few surprises in this regard. Specifically, I saw a woman in her 40s who at 5 feet 3 inches hardly resembled your average patient with Marfan syndrome and yet had cardiac, eye and spinal findings that confirmed this unlikely diagnosis. I also examined a tall yet stocky (lumber jack like) fellow who ruptured his aorta at the age of 36 while hoisting tires in the factory. It was truly a miracle that he survived this event and on clinical grounds one would never suspect this diagnosis. Interestingly, his affected teen-aged son who came for a check up had the long thin build we would expect to see with this condition. My final anecdote relates to a 65 year old patient admitted to the medical service for her second spontaneous pneumothorax. At 5 foot 7 inches and with an early kyphosis she did not really have a striking marfanoid build. However, she did have long fingers and in light of her pulmonary problems, Marfan syndrome came to mind. It was only when we got the family history that we knew we were onto something since her brother had died at a relatively early age from a ruptured aortic aneurysm.

In light of the confounding clinical features, how is one to reasonably recognize or suspect the diagnosis of Marfan syndrome? Which individuals deserve that $3500 work up and who is just tall and thin? Fortunately in 1996 a group of thoughtful clinicians got together and published the "Revised Diagnostic Criteria for the Marfan Syndrome" in the American Journal of Medical Genetics 62:417-426. Although I wouldn't recommend this for late night reading, the complexity of this multisystem disorder is outlined very clearly in this article and provides some guidance for us when faced with a patient who may be affected.

Because of the wide variability in the expression of this condition and relatively high rate of new mutations (15-20%) in patients presenting for care, the family history is not always helpful. The most compelling reason to pursue this diagnosis is the relatively high risk for sudden death in fairly young people who carry one of these gene mutations. Careful monitoring of the aortic root diameter with prophylactic surgery when indicated has dramatically reduced the death rate in patients with Marfan syndrome. Pregnancy management is especially important in women with this condition because of the risks of aortic root dilatation and/or rupture both prenatally and during labor.

Here are some of the clinical findings listed by system and divided into major and minor criteria. Since many normal people have some of these features, it is only in seeing a number of these findings in a given individual that one would consider this possible diagnosis.

Although the incidence of Marfan syndrome is estimated to be about 1 in 10,000 individuals, it is very likely that the incidence is greater because of poor ascertainment. For many families the first clue to this diagnosis comes from the tragic death of a young person from aortic rupture. It is only then that other affected relatives are identified who may benefit from careful cardiac surveillance and possibly even reduce their risks for aortic root dilatation by after load reduction through use of a beta-blocker.

Because DNA testing for Marfan syndrome is quite complex due to many, many different fibrillin mutations, diagnosis in 1999 is still primarily made through conscientious clinical investigations. For a patient with enough clinical features to warrant an evaluation I would recommend the following:

• Careful three generation family history concentrating on major medical findings such as aortic aneurysms, aortic rupture, unexplained sudden death, severe scoliosis, spontaneous pneumothoraces and high myopia +/- retinal detachments.

• Echocardiogram looking carefully at the aortic root diameter, mitral valve and pulmonary valve.

• Dilated eye exam by a knowledgeable ophthalmologist looking for subtle lens subluxation, corneal flattening or hypoplasia of the ciliary muscle or iris.

• Careful clinical exam with upper to lower segment ratio, arm span, wrist/thumb sign assessment, skin exam, assessment for possible scoliosis, pes planus or pectus deformity.

By identifying those adult patients at high risk for Marfan syndrome, one can potentially add years to their lives and provide vital information to close family members. Patients who are identified with this condition need close cardiac follow-up, eye care and may benefit from genetic counseling. Over time we hope that through research we may be able to eventually improve outcome for affected individuals; recent efforts have paved the way for future discoveries and even better medical interventions.

For providers who are already following a patient with Marfan syndrome, the American Academy of Pediatrics has published "Health Supervision for Children with Marfan Syndrome" Pediatrics 98(5): 978-982, 1996. You can also access these guidelines through our website under Clinical Links, AAP Committee on Genetics. Even though this statement addresses the needs of children, it is also applicable to many of the issues faced by adults with Marfan syndrome.