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Last updated: 1/21/2025
Years published: 1984, 1985, 1987, 1988, 1989, 1990, 1992, 1994, 1995, 1997, 1999, 2002, 2003, 2007, 2008, 2011, 2014, 2017, 2021, 2025
NORD gratefully acknowledges Hal Dietz, MD, Victor A. McKusick Professor of Medicine and Genetics, McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, for assistance in the preparation of this report.
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Marfan syndrome is a genetic disorder that affects connective tissue, which is the material between cells of the body that gives the tissues form and strength. Connective tissue is found all over the body and multiple organ systems may be affected in individuals with Marfan syndrome. The heart and blood vessels (cardiovascular), skeletal and eye (ocular) systems are most often affected. Major symptoms include overgrowth of the long bones of the arms and legs, abnormal side-to-side curvature of the spine (scoliosis), indentation or protrusion of the chest wall (pectus deformity), dislocation of the lenses of the eyes (ectopia lentis), nearsightedness (myopia), widening (aneurysm) and tear (dissection) of the main artery that carries blood away from the heart (aorta), floppiness of the mitral valve (mitral valve prolapse) and backward flow of blood through the aortic and mitral valves (aortic and mitral regurgitation). The specific symptoms and the severity of Marfan syndrome vary greatly from person to person. Marfan syndrome is caused by changes (variants) in the fibrillin-1 (FBN1) gene. The condition follows an autosomal dominant inheritance pattern, meaning that only one copy of a FBN1 gene variant is sufficient to cause the condition.
The specific symptoms of Marfan syndrome vary greatly from person to person. Some individuals will develop only a few mild or isolated symptoms; others will develop more serious complications. In most people, Marfan syndrome progresses as individuals grow older. In some infants, Marfan syndrome may cause severe, rapidly progressive complications during infancy, often quickly affecting multiple organ systems early in life. Marfan syndrome can potentially affect many systems of the body including the heart, blood vessels, skeleton, eyes, lungs and skin.
Individuals with Marfan syndrome often develop distinct physical findings including an abnormally thin physique and disproportionately long, slender arms and legs (dolichostenomelia) due to overgrowth of the long bones. In addition, affected individuals usually have abnormally long, slender fingers (arachnodactyly). People with Marfan syndrome are usually very tall and thin in comparison to unaffected family members but not necessarily in comparison to the general population. They can lack muscle tone (hypotonia) and have little fat under the skin (subcutaneous fat).
A variety of skeletal malformations affect individuals with Marfan syndrome including overgrowth of the ribs, which can push the breastbone (sternum) inward resulting in a sunken chest (pectus excavatum) or outward resulting in a protruding chest (pectus carinatum). Additional symptoms include abnormally loose or flexible joints (joint hypermobility), flat feet (pes planus), fingers that are permanently bent or โfixedโ and cannot extend or straighten fully (camptodactyly or clinodactyly), and reduced extension of the elbow. In some people, the joints may be unaffected or may become tight and stiff (contractures). Some individuals have an abnormally deep hip socket (acetabulum) with deep insertion of the head of the long bone (femur) of the leg (protrusio acetabulae) and signs of bone erosion. Many individuals with Marfan syndrome develop spinal abnormalities such as progressive curving of the spine (scoliosis) that may be mild or severe. Scoliosis may be associated with back pain in some affected individuals. In children, skeletal abnormalities may progress rapidly during phases of rapid growth, such as adolescence.
Individuals with Marfan syndrome may have several distinct facial features including a long, narrow skull (dolichocephaly), deep-set eyes (enophthalmos), an abnormally small jaw (micrognathia) that may be recessed farther back than normal (retrognathia), abnormally flat cheek bones (malar hypoplasia) and a downward slant to the eyes (downward slanting palpebral fissures). Affected individuals may also exhibit a highly arched roof of the mouth (palate), teeth that are crowded together and upper and lower teeth that do not meet (align) properly when biting (malocclusion).
Individuals with Marfan syndrome may have significant cardiovascular problems such as a common heart defect known as mitral valve prolapse. The mitral valve is located between the left upper and left lower chambers (left atrium and left ventricle, respectively) of the heart. Mitral valve prolapse occurs when one or both flaps (cusps) of the mitral valve bulge or collapse backward (prolapse) into the left upper chamber (atrium) of the heart during ventricular contraction. In some people, this may allow leakage or the backward flow of blood from the left lower chamber of the heart (ventricle) back into the left atrium (mitral regurgitation). Often no associated symptoms are apparent (asymptomatic). However, mitral valve prolapse can result in chest pain, abnormal heart rhythms (arrhythmias), or evidence of inadequate heart function (congestive heart failure, most often in association with prolonged and severe mitral regurgitation).
Additional cardiovascular findings include widening (aneurysm) and degeneration of the main artery that carries blood away from the heart (aorta), tearing (dissection) of the aorta so that blood seeps between the inner and outer layers of the aortic wall and backward flow of blood from the aorta into the lower left chamber (ventricle) of the heart (aortic regurgitation). If severe and left untreated, these heart abnormalities associated with Marfan syndrome can cause life-threatening complications such as rupture of the aorta and congestive heart failure. Some individuals may develop widening of the main artery of the lungs (pulmonary artery dilatation). This typically does not cause any problems in people with Marfan syndrome.
Individuals with Marfan syndrome commonly develop abnormalities of the eyes, especially nearsightedness (myopia), which may develop early in childhood and become progressively worse. Approximately 60 percent of individuals develop displacement of the lenses of the eyes away from the center of the eye (ectopia lentis). Ectopia lentis may occur at birth or later in life and may remain stable or become progressively worse.
Additional issues affecting the eyes in Marfan syndrome include an abnormally flat cornea (the front portion of the eyes through which light passes), underdevelopment of the colored portion of the eye (hypoplastic iris) and detachment of the nerve-rich membrane (retina) lining the back of the eyes. Some individuals with Marfan syndrome are at risk for the early development of clouding of the lenses of the eyes (cataracts) or increased pressure and/or associated changes in the eyes (glaucoma). If left untreated, eye abnormalities can result in vision loss.
Some individuals with Marfan syndrome may develop distended air pockets near the top of the lungs (apical pulmonary blebs) which can predispose individuals to a leak of air within the chest cavity and lung collapse that occurs for no readily apparent reason (spontaneous pneumothorax). In some people, pneumothorax can recur in the same lung or even the opposite lung (recurrent pneumothorax). Marfan syndrome can be associated with blockage of the upper airway during sleep (obstructive sleep apnea) that can impair lung and heart function if severe and left untreated.
Some affected individuals may develop widening or bulging of the sac (dura) that surrounds the spinal cord (dural ectasia). This condition usually does not cause symptoms (asymptomatic) but has been associated with lower back pain and can cause pinching of a nerve leading to abnormal sensations or muscle performance in the legs. Affected individuals may also developed stretch marks (striae atrophicae) of the skin without an obvious cause. Some affected individuals may have an inguinal, umbilical or surgical hernia, in which a weakened portion of the pelvic or abdominal wall shows external bulging, sometimes allowing protrusion of a small segment of the intestines.
Marfan syndrome is caused by changes (variants) in the FBN1 gene. Not everyone who has a variant in this gene develops Marfan syndrome. Some changes do not alter the function of the gene or protein and therefore do not cause a medical problem. Other changes in the FBN1 gene can cause conditions that are distinct from Marfan syndrome.
The FBN1 gene contains instructions for producing (encoding) a protein known as fibrillin-1. Fibrillin-1 is a component of structures called microfibrils, which are fiber-like structures that are part of the extracellular matrix, a complex material that surrounds and connects cells throughout the body. Researchers think fibrillin-1 plays an essential role in maintaining the strength and structural integrity of the connective tissue. Without fibrillin-1, connective tissue may be weak. Current evidence also suggests that fibrillin-1 also influences the activity of molecules that instruct cells how to behave (growth factors), including a specific growth factor called transforming growth factor-ฮฒ (TGF-ฮฒ).
Marfan syndrome is inherited as an autosomal dominant condition. Dominant genetic disorders occur when only a single copy of a disease-causing gene variant is necessary to cause the disease. The gene variant can be inherited from either parent or can be the result of a new (de novo) changed gene in the affected individual that is not inherited. The risk of passing the gene variant from an affected parent to a child is 50% for each pregnancy. The risk is the same for males and females.
Marfan syndrome affects males and females in equal numbers and occurs worldwide with no ethnic predisposition. The prevalence has been estimated to be about 1 in 10-15,000 individuals in the general population. Because of the difficulty in diagnosing mild cases of Marfan syndrome, the disorder is probably underdiagnosed.
No universal, specific diagnostic test exists for Marfan syndrome despite the identification of the causative gene. A diagnosis is made based upon a detailed patient and family history, a thorough clinical evaluation, and a variety of specialized tests performed to identify key findings associated with Marfan syndrome. Different criteria have been proposed for classifying someone as having Marfan syndrome. The most recent published criteria (the revised Ghent nosology) were published in 2010. According to these guidelines, the presence of aortic root aneurysm, eye lens dislocation, or a family history of definite Marfan syndrome weigh heavily in the diagnosis of Marfan syndrome, with an additional potential contribution of other findings throughout the body. Molecular testing (e.g. looking for a variant in the FBN1 gene) can aid in the diagnosis of Marfan syndrome, but identifying a variant is not sufficient to establish the diagnosis in the absence of sufficient physical findings or family history.
Individuals suspected of having Marfan syndrome will usually undergo a complete skeletal examination, a heart examination including a test that uses sound waves to produce images of the heart (echocardiogram) and a specialized examination of the eyes (slit-lamp eye examination). A slit-lamp allows an eye doctor to examine the eyes under high magnification to detect lens dislocation and other eye issues. It is essential that this comprehensive diagnostic evaluation be coordinated by someone very familiar with Marfan syndrome and related diagnoses.
Treatment
The treatment of Marfan syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists including geneticists, surgeons, cardiologists, dental specialists, eye specialists (ophthalmologists), orthopedists and other healthcare professionals.
Individuals with Marfan syndrome are encouraged to avoid competitive and contact sports, heavy lifting and any exercise that increases the strain on the aorta produced by rapid or vigorous beating of the heart or increased blood pressure. Restriction of such activities can slow the rate of the widening of the aorta (aortic dilatation) and decrease the tendency for aortic tear (dissection). In general, moving types of exercises performed in moderation are thought to be good for people with Marfan syndrome. Such exercises, performed regularly, will naturally lower heart rate and blood pressure.
Beta-adrenergic receptor blocking drugs (ฮฒ-blockers) such as propranalol or atenolol are often used in treating the cardiovascular problems associated with Marfan syndrome. Such drugs help to reduce the strength and frequency of the contractions of the heart and lower blood pressure. In doing so, they may reduce the strain on the walls of the aorta. Beta-blockers may delay the need for heart surgery. The dosage needs to be adjusted to the individual patientโs needs, and therapy should be closely monitored. Some individuals may not be able to tolerate these drugs and others such as those with asthma or depression may not be able to take them (contraindicated).
A second class of blood pressure medication called angiotensin receptor blockers (ARBs) is commonly used in the treatment of cardiovascular problems associated with Marfan syndrome. This includes medications such as losartan or irbesatan. There is experimental evidence that ARBs can help by both lowering blood pressure and by blocking TGF-ฮฒ activity. In animal models of Marfan syndrome, the protective effects of ARBs was superior to that seen with ฮฒ-blockers. In clinical trials, ARBs have variably been shown to be either better than or as good as ฮฒ-blockers in suppressing aneurysm growth, but this may not be true for all patients or in all circumstances. In the largest trial performed to date, young patients receiving ฮฒ-blockers (at high dosing) or ARBs (at standard dosing) had a comparable decline in the deviation of the aortic root size from that expected for age and body size (decreasing aortic root z-score). While both treatments were well tolerated in this study, in general, ARBs are thought to be better tolerated than ฮฒ-blockers. A recent analysis of all of the participants in most of the largest clinical trials for Marfan syndrome (meta-analysis) documented that ARBs such as losartan or irbesartan can decrease the rate of aortic root growth in individuals with Marfan syndrome. On average, this treatment halved the rate of aortic root growth when compared to individuals who were not receiving medical therapy, with an even greater treatment effect in people that had a documented FBN1 gene variant. It is the stated position of the Marfan Foundation that the choice of treatment should be guided by the particular circumstances. A combination of ฮฒ-blocker and ARB therapy can be considered in circumstances where one or the other type of medication does not achieve an adequate response.
Every person with Marfan syndrome should have at least a yearly echocardiogram to check the size and function of the heart and aorta. Surgical repair of the aorta may eventually become necessary if the aorta has severely widened or developed a tear (dissection). Preventive (prophylactic) surgery is recommended when the diameter of the aorta reaches 5 centimeters in older children or adults, when the rate of widening reaches 1 centimeter a year, or when there is severe or progressive backflow (regurgitation) of blood through the aortic valve. Surgery may also be necessary for leakage of the mitral valve. Replacement of the aortic valve with an artificial valve may be performed (composite graft repair); however, this surgery requires the lifelong use of medications to prevent blood clots (anticoagulation). In recent years, some physicians have preferred to use valve-sparing surgery (i.e., reimplantation of the natural aortic valve within a Dacron tube used to replace the enlarged segment of the aorta). Studies are underway to assess the durability of valve-sparing procedures, but early-to-intermediate data are encouraging.
Surgery to repair or replace the mitral valve in individuals who experience severe mitral valve regurgitation may become necessary. Cardiovascular problems related to Marfan syndrome increase susceptibility to repeated bacterial infections such as infections of the heart valves (bacterial endocarditis). Leaking heart valves are more prone to infection with bacteria. While it had been common practice to treat patients with leaking valves with antibiotics before dental work or other procedures expected to contaminate the blood stream with bacteria, the American Heart Association recently withdrew this recommendation for most people. Given the predisposition of people with Marfan syndrome and other connective tissue disorders to progressive leakage through multiple heart valves, many physicians who routinely care for such individuals continue to recommend that antibiotics be used before dental work or other procedures expected to introduce bacteria into the bloodstream.
Skeletal abnormalities such as scoliosis and deformity of the chest may represent serious problems for people with Marfan syndrome. Braces may be tried to correct skeletal curving (scoliosis) in some people but can be ineffective. Individuals with curvature of the spine of more than 10 degrees should be followed by an orthopedist. Surgical stabilization of the spine may be needed if the curvature is severe or progressive. A sunken chest (pectus excavatum) may be surgically corrected for cosmetic reasons or, in very rare severe cases, to avoid medical complications.
The eyes require careful attention (e.g., yearly ophthalmologic exams) from early childhood. Failure to detect any of the several abnormalities that can affect the eyes may result in poor vision and other visual impairment. Increased risk of retinal detachment does demand special attention. The eyes should receive special protection from injury during work or sports. Sports that may involve trauma to the head, such as football, boxing and diving, should be avoided. Displacement of the lenses may be treated with eyeglasses or contact lenses. Some individuals such as those with a completely loose lens or with a displaced lens that disrupts vision may require surgical intervention. A detached retina can sometimes be corrected, especially if detected early.
Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact: www.centerwatch.com
For information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
Contact for additional information about Marfan syndrome:
Hal Dietz, MD
Victor A. McKusick Professor of Medicine and Genetics
Department of Genetic Medicine
Departments of Pediatrics, Medicine, and Molecular Biology & Genetics
Johns Hopkins University School of Medicine
733 N. Broadway, BRB 539
Baltimore, MD 21205
(410) 614-0701
(410) 614-2256 (fax)
[email protected]
TEXTBOOKS
Dietz H. Marfan Syndrome. NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:218-9.
JOURNAL ARTICLES
Loeys BL, Dietz HC, Braverman AC, et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet. 2010;47:476-485.
Dean JC. Marfan syndrome: clinical diagnosis and management. Eur J Hum Genet. 2007;15:274-33.
Forteza A, Cortina JM, Sanchez V, et al. Aortic valve preservation in Marfan syndrome. Initial experience. Rev Esp Cardiol. 2007;60:471-5.
Ramirez F, Dietz HC. Marfan syndrome: from molecular pathogenesis to clinical treatment. Curr Opin Genet Dev. 2007;17:252-8.
Judge DP, Dietz HC. Marfanโs syndrome. Lancet. 2005;366:1965-76.
Gott VL, Cameron DE, Alejo DE, et al. Aortic root replacement in 271 Marfan patients: a 24-year experience. Ann Thorac Surg. 2002;73:438-43.
Le Parc JM, Molcard S Tubach F, et al. Marfan syndrome and fibrillin disorders. Joint Bone Surg. 2000;67:401-7.
Collod G, Babron M-C, Jondeau G, et al. A second locus for Marfan syndrome maps to chromosome 3p24.2-p25. Nat Genet. 1994;8:264-8.
Dietz HC, Pyeritz RE, Hall BD, et al. The Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature. 1991;352:337-9.
Sakai LY, Keene DR, Engvall E. Fibrillin, a new 350-kD glycoprotein, is a component of extracellular microfibrils. J Cell Biol. 1986;103:2499-509.
INTERNET
Defendi GL. Genetics of Marfan syndrome. Medscape. Last Update: Jun 16, 2023. https://www.emedicine.com/ped/topic1372.htm Accessed January 21. 2025.
Inna P. Marfan syndrome. Medscape. Last Update: Jul 01, 2024. https://www.emedicine.com/orthoped/topic414.htm Accessed January 21, 2025.
Dietz H. FBN1-Related Marfan Syndrome. 2001 Apr 18 [Updated 2022 Feb 17]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviewsยฎ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1335/ Accessed January 21, 2025.
Jondeau G. Marfan syndrome. Orphanet encyclopedia, March 2010. Available at: https://www.orpha.net/en/disease/detail/558?name=marfan&mode=name Accessed January 21, 2025.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Marfan Syndrome; MFS. Entry No: 154700. Last Edited 09/25/2022. Available at: https://omim.org/entry/154700 Accessed January 21, 2025.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Loeys-Dietz Syndrome, Type 2B; LDS2B (Marfan Syndrome, Type II, Formerly). Entry No: 610168 Last Updated 10/03/2023. Available at: https://omim.org/entry/610168 Accessed January 21, 2025.
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The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
View reportOnline Mendelian Inheritance In Man (OMIM) has a summary of published research about this condition and includes references from the medical literature. The summary contains medical and scientific terms, so we encourage you to share and discuss this information with your doctor. OMIM is authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine.
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