The UCSF Heart and Vascular Center has opened a clinic specializing in Marfan syndrome and related disorders as part of the new UCSF Program in Cardiovascular Genetics. The program, which is directed by geneticist Robert Nussbaum, M.D., and genetic counselor Colleen Brown, is also inaugurating clinics in familial cardiomyopathies and in genetic arrhythmias.
The cardiovascular genetics program is an example of a growing trend: greater integration of the field of genetics into adult medicine. As the knowledge about genetic mechanisms of disease advances and new molecular tests and therapies are developed, geneticists and genetic counselors are moving from simply serving as consultants to becoming full partners with their colleagues in other medical subspecialties. Genetics in cardiology is one of the newest and fastest growing areas in medicine, and UCSF's program is one of the first on the West Coast.
"This is an organized program where there is a high level of expertise in the diagnosis and care of these patients, and we can offer new therapies and treatments as soon as they are available," says Nussbaum. "Also, with our emphasis on family outreach, the families receive the counseling and care they need. The entire family is our patient, not just the individual in front of us."
Marfan syndrome affects 40,000 people in the United States. Sometimes, a person with Marfan syndrome is the first in his or her family with the disease. Frequently, however, the condition is inherited from an affected parent. Each child of a person with Marfan syndrome has a 50 percent chance of inheriting the disorder.
Once the diagnosis is made in one person in a family, it is important to evaluate relatives for Marfan syndrome because they can develop life-threatening aortic aneurysms. Signs of the disease vary widely, and someone may have the mutation, but display few obvious signs. A thorough physical examination, supplemented by genetic testing and echocardiography, often provides a definitive diagnosis.
Marfan syndrome is caused by a mutation in the fibrillin-1 (FBN1) gene, which codes for an important component of connective tissue. The disorder affects the skeleton, eyes, nervous system, skin, lungs, heart and blood vessels. Many patients are exceptionally tall, slender, loose-jointed, and have long fingers and toes and a long, narrow face. Both orthopaedic and eye disorders are common. The most life-threatening complications are the cardiovascular sequelae associated with Marfan syndrome, which may lead to aortic dissection, severe mitral regurgitation and heart failure.
UCSF's Marfan syndrome clinic is unique because, in a single day, every patient receives a full evaluation and sees every relevant specialist, including a geneticist, cardiologist, orthopedist and ophthalmologist. Each of these assessments contributes to the diagnostic evaluation. The goal is to complete all relevant evaluations in a coordinated and integrated fashion, so that families leave the hospital with a diagnosis and comprehensive medical plan.
"It can be a huge burden and very overwhelming for these families when they have so many specialists to see," says Brown.
A typical day for a patient visiting the Marfan syndrome clinic starts at 8:30 a.m. First, Nussbaum and Brown take family and medical histories, and review information from referring physicians. This initial evaluation is followed by an echocardiogram to assess aortic dilatation, followed by a visit with cardiologist Eduardo Rame, M.D., who does a cardiovascular assessment. The patient then sees an orthopedist, who takes X-rays and performs a skeletal exam specifically for Marfan syndrome. In the afternoon, the patient sees an ophthalmologist for a Marfan syndrome-specific eye exam.
"If a patient with Marfan syndrome and dilatation of the proximal aorta is followed in our clinic, we look for signs that the aorta is unstable," says Rame. "For example, if the aorta has dilated from 3.5 centimeters to 4 to 4.5 centimeters over two years, they have a high risk of dissection."
Medical therapies such as beta-adrenergic receptor blockers (beta blockers) are used to decrease the wall stress on the aorta in order to prevent further progressive dilatation and events such as aortic dissection and aortic rupture. If it is determined that progressive dilatation is inevitable despite maximal medical therapies, a recommendation of early surgical intervention to repair the aorta is made.
"Our clinic provides an overall risk assessment for the aorta," says Rame. "Then we follow up with the referring physician to be sure we agree on clinical decisions, such as medications and/or surgical interventions. For patients who do not have a fully defined syndrome or who are being evaluated for the first time, our multidisciplinary approach to the patient provides a significant advantage when we are integrating the findings from the cardiovascular evaluation to the overall clinical syndrome."
At the end of the day, the patient meets with Nussbaum and Brown again, who by that time have analyzed reports from all of the specialists. They consult with Rame to devise a diagnosis and comprehensive medical plan. If the diagnosis is not definitive, the appropriate genetic testing is done. The results are available a few weeks later. A letter is then sent to the family to offer counsel and to state which family members should get tested. A second report is sent to the referring physician with the diagnostic results and recommended treatment.
The Marfan syndrome clinic also will foster research programs to discover genes that lead to similar disorders, such as familial aneurysm, for which all of the causative genes have not been identified. Nussbaum and Brown are therefore researching families' genetic makeup to expand knowledge about hereditary vascular conditions and hopefully identify new disorders.
"By researching families with familial aneurysm, we can apply a number of powerful molecular genetic tools to track down the genes responsible," says Nussbaum. "And if we can do that, perhaps we can understand why the aneurysms occur and possibly develop new methods of diagnosis and therapy. The whole idea is to prevent an aneurysm from developing."
Nussbaum and Brown work with referring physicians throughout the evaluation process and recommend that physicians refer patients to UCSF if they have any suspicion that their patients have Marfan syndrome or a disorder that resembles Marfan syndrome.
For more information about the Program in Cardiovascular Genetics, contact genetic counselor Colleen Brown at (415) 476-3202.
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