In 1896, the pediatrician Dr. Antoine Bernard-Jean Marfan described the exceptionally long, slender limbs and physique of a 5-year-old girl, Gabrielle P., in front of the Medical Society of the Hospital of Paris (Enersen). It is unknown whether Gabrielle P. actually suffered from what is now known to be Marfan syndrome, but Dr. Henricus Jacubus Marie Weve was recognized as the first person to use the term ‘Marfan syndrome’ to describe this common genetic disorder.
In the decades leading up to Dr. Weve’s use of Marfan syndrome to describe a patient’s symptoms in 1931, other physicians had begun to document their encounters with this disease with the benefit of radiological images (Enersen). Drs. Henri Mery and Leon Baonneix studied Gabrielle P. anew using this new technology in 1902 and noted a misaligned spine, thoracic asymmetry, long digits, cardiovascular abnormalities, and dislocation of the ocular lens. During the same year, Dr. Achard described a patient with similar characteristics, including joint hypermobility and a pattern of family inheritance.
The estimated prevalence of Marfan syndrome can range between 1:3,000 (Lavall, Schafers, Bohm, and Laufs 228), 1:5,000 (NAIMS “What is Marfan Syndrome?”), and 1:10,000 (Dean 724). The lowest estimate by Lavall and colleagues assumes a significant number of people with Marfan syndrome remain undiagnosed (228). The prevalence of this disorder dies not seem be influenced by gender or ethnicity (NAIMS “What is Marfan Syndrome?”).
Marfan syndrome is an autosomal dominant genetic disorder, and in most cases transmitted from parent to offspring (NIAMS, “What causes Marfan Syndrome”). Therefore, one of the cardinal features of the disorder is a family history. The common physical features include exceptionally long limbs and digits, exceptional height, high palate, eye lens dislocation, thoracic asymmetry, hyper-flexible joints, and susceptibility to cardiac deformities (Beighton 403-404). However, a definitive diagnosis is not always straightforward, since manifestation of the disease can vary considerably between individuals. For example, only 50% of patients are predicted to suffer from a lateral curvature of the spine (scoliosis). Other symptoms can include poor muscle development, little fat tissue, hernias, and lung disease (Thurmon 243).
Adding to the difficulty of diagnosing this disorder is that many of these symptoms can appear as part of other genetically-distinct syndromes (Thurmon 242). These other syndromes include contractural arachnodactyly, Marfan-like connective tissue disorder, and several diseases resulting from collagen abnormalities. Marfan-like symptoms can also emerge due to acquired medical conditions and simply by chance. For example, extreme tallness and the heart defect mitral prolapse occur in the general population at rates of 3% and 6%, respectively, so physicians will eventually encounter both occurring in the same individual, but in the absence of Marfan syndrome.
One of the most common features of Marfan syndrome is ectopia lentis, which occurs when the lens of the eye becomes detached at one or more locations (Thurmon 243). This results in the lens tilting into the vitreous humor and causing vision problems. This can be easily observed in approximately 50% of adult patients and is detectable in close to 80% of adults with the proper vision test.
Another common symptom is cardiovascular defects (Missimini 633). Those of primary concern are mitral valve prolapse and aortic aneurysms. The mitral valve is important for controlling blood flow into the aorta, and if it does not function properly then the blood will flow in the wrong direction. Mitral valve prolapse can be identified in some Marfan syndrome patients at birth, but in most by age 10 (Thurmon 243). Aortic aneurysms develop when the aortic vessel expands, leading to a weakening of the vessel wall and eventual rupture (dissection). Aortic aneurysms tend to develop adjacent to the heart first and then expand towards the periphery. Some patients will experience chest pain (angina) as an early sign. Aortic insufficiency is common by the time patients reach puberty and tears can develop in women who become pregnant. Approximately 75% of Marfan syndrome patients will develop cardiac problems and this has a significant impact on life expectancy (Lavall, Schafers, Bohm, and Laufs 228-229). Most deaths due to an aortic rupture occur after the age of 20, with an average of 32 years (Thurmon 243); however, these statistics are for patients not being treated (Lavall, Schafers, Bohm, and Laufs 229). With proper treatment, patients can live as long as 60 years.
Marfan syndrome is caused by genetic mutations in the fibrillin-1 gene, a gene that produces a protein important for proper functioning of connective tissue (NIAMS, “What causes Marfan Syndrome”). Approximately 75% of all cases are inherited from a parent who carries the mutated gene. The parent would also show signs of Marfan syndrome. The other 25% of cases are caused by spontaneous mutations in the fibrillin-1 gene during the formation of sperm or eggs in the parents, therefore the parents of these children do not have Marfan syndrome.
The fibrillin-1 gene produces a 350 kD glycoprotein that becomes an essential component of the extracellular matrix, where it polymerizes to form microfibrils (Dean 728-729). In addition to providing structural support to tissue, these microfibrils sequester proteins of the transforming growth factor ? (TGF?) — family. This process of sequestration prevents this growth factor family from being released and exerting its effects on the neighboring cells. Due to the mutations in the fibrillin-1 gene though, this TGF? ‘sink’ is often compromised, resulting in excess TGF? affecting cellular function in detrimental ways. Although a defective fibrillin-1 protein may cause some structural problems, it is now believed that this excess TGF? is primarily to blame for Marfan symptoms. How this occurs remains unknown.
Diagnosis remains difficult in some cases, because of the considerable variability in symptoms (NMF “About Marfan Syndrome: Diagnosis.”). Diagnosis in most cases still depends on a taking a family history, performing a physical examination of the patient, and administering the following tests: echocardiogram, electrocardiogram, eye exam, and imaging of the lower back. The intense diagnostic focus on cardiovascular problems represents how threatening these defects are to the patient’s health and the need for immediate intervention. Imaging of the lower back is diagnostically useful because many Marfan patients develop dural ectasias, which are an expansion of the membrane encasing the spinal cord (England). In Marfan patients, this membrane commonly expands, causing lower back pain, and can sometimes herniate into the area around the spinal column.
The genetic disorder Loeys-Dietz has been recently discovered and its symptoms overlap considerably with Marfan syndrome (NAIMS “How is Marfan Syndrome Diagnosed). For this reason, it is important to distinguish between the two because the risk of dying from heart defects is greater for Loeys-Dietz patients and the treatment differs significantly. However, in contrast to Marfan syndrome, a diagnostic test is available for Loeys-Dietz syndrome.
Although genetic testing can be done to detect mutations in the fibrillin-1 gene, it may not provide any additional information (NAIMS “How is Marfan Syndrome Diagnosed). In addition, between 9% and 34% of Marfan patients have fibrillin-1 mutations that have not been characterized yet and therefore cannot be tested for (Dean 725). Given the large number of fibrillin-1 mutations that can cause Marfan syndrome and an unknown number that have yet to be identified, the development of a definitive diagnostic test for Marfan syndrome may occur for some time.
Marfan syndrome patients can live longer and enjoy a healthier lifestyle with treatment by a specialist (Massimini 634-635). The function and size of the heart and aorta should be checked annually by echocardiogram. A comprehensive eye exam should be performed, followed by regular checkups at a qualified ophthalmologist. The development of the skeletal system should be monitored during childhood and checked regularly during adulthood. The control of blood pressure is important to reduce the stress on the heart and aorta and antibiotics may be prescribed in advance of dental or genitor-urinary procedures to prevent infections in patients with a prolapsed mitral valve or a history of heart surgeries. Blood-thinning medications will likely be prescribed for patients who have had aortic surgery, such as the repair of a rupture.
Marfan patients also need to pay attention to how they cope with everyday life (Massimini 635-638). It is important to avoid strenuous exercise, contact sports, or lifting heavy objects. Any exercise regimen should be discussed with a physician in advance to avoid overexertion and to become familiar how heart medications can impact physical activity. For example, the anticoagulant Coumadin is often prescribed for patients who have had a heart valve replacement, which can increase the possibility of internal bleeding and bruising.
Recommended activities include walking briskly, bicycling or jogging at a slow pace, shooting baskets, a relaxed tennis game, and 1-3 pound hand weights. The amount of activity should be limited to less than 30 minutes, 3 to 4 times per week.
Famous People with Marfan Syndrome
Having Marfan syndrome has not impeded the lives and careers of a large number of people around the world (NMF “About Marfan Syndrome: Notable Individuals & #8230;”). The actor Vincent Schiavelli was diagnosed with Marfan syndrome…