Send to

Choose Destination

Marfan Syndrome.


Dietz H1,2,3.


GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.
2001 Apr 18 [updated 2017 Oct 12].

Author information

Victor A McKusick Professor, Pediatrics, Medicine, and Molecular Biology & Genetics, Institute of Genetic Medicine
Director, Smilow Center for Marfan Syndrome Research
Investigator, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland



Marfan syndrome, a systemic disorder of connective tissue with a high degree of clinical variability, comprises a broad phenotypic continuum ranging from mild (features of Marfan syndrome in one or a few systems) to severe and rapidly progressive neonatal multiorgan disease. Cardinal manifestations involve the ocular, skeletal, and cardiovascular systems. Ocular findings include myopia (the most common ocular feature); ectopia lentis (seen in approximately 60% of affected individuals); and an increased risk for retinal detachment, glaucoma, and early cataracts. Skeletal system manifestations include bone overgrowth and joint laxity; disproportionately long extremities for the size of the trunk (dolichostenomelia); overgrowth of the ribs that can push the sternum in (pectus excavatum) or out (pectus carinatum); and scoliosis that ranges from mild to severe and progressive. The major morbidity and early mortality in the Marfan syndrome relate to the cardiovascular system and include dilatation of the aorta at the level of the sinuses of Valsalva (predisposing to aortic tear and rupture), mitral valve prolapse with or without regurgitation, tricuspid valve prolapse, and enlargement of the proximal pulmonary artery. Severe and prolonged regurgitation of the mitral and/or aortic valve can predispose to left ventricular dysfunction and occasionally heart failure. With proper management, the life expectancy of someone with Marfan syndrome approximates that of the general population.


The diagnosis of Marfan syndrome is established in a proband (by definition, a person without a known family history of Marfan syndrome) who has one of the following sets of findings: An FBN1 pathogenic variant known to be associated with Marfan syndrome AND one of the following: Aortic root enlargement (Z-score ≥2.0). Ectopia lentis. Demonstration of aortic root enlargement (Z-score ≥2.0) and ectopia lentis OR a defined combination of features throughout the body yielding a systemic score ≥7.


Treatment of manifestations: Comprehensive management by a multidisciplinary team including a clinical geneticist, cardiologist, ophthalmologist, orthopedist, and cardiothoracic surgeon is strongly recommended. Treatment typically includes spectacle correction for refractive errors and sometimes, surgical removal of a dislocated lens with artificial lens implantation (preferably after growth is complete). Scoliosis may require surgical stabilization; repair of pectus deformity is largely cosmetic. Orthotics and arch supports can lessen leg fatigue, joint pain, and muscle cramps associated with pes planus. Surgical repair of the aorta is indicated when the maximal measurement of the aortic root approaches 5.0 cm in adults or older children, the rate of increase of the aortic root diameter approaches 0.5-1.0 cm per year, or there is progressive and severe aortic regurgitation. For younger children, aortic root surgery should be considered once: (1) the rate of increase of the aortic root diameter approaches 0.5-1.0 cm per year, or (2) there is progressive and severe aortic regurgitation. Severe and progressive mitral valve regurgitation with attendant ventricular dysfunction is the leading indication for cardiovascular surgery in children with Marfan syndrome. Afterload-reducing agents can improve cardiovascular function when congestive heart failure is present. Prevention of primary manifestations: Medications that reduce hemodynamic stress on the aortic wall, such as use of beta blockers (β-blockers) or angiotensin receptor blockers (ARBs) together, are generally initiated at diagnosis or upon documentation of significant and/or progressive aortic dilatation. Other antihypertensive agents can be used if β-blockers and ARBs are not tolerated; however, evidence as to their efficacy and safety in Marfan syndrome is under investigation. Prevention of secondary complications: Subacute bacterial endocarditis prophylaxis for dental work with the presence of mitral or aortic valve regurgitation. Surveillance: Annual ophthalmologic examination; annual echocardiography to monitor the status of the ascending aorta when aortic dimensions are small and/or the rate of aortic dilation is slow; more frequent examinations are indicated when the aortic root diameter exceeds approximately 4.5 cm in adults, rates of aortic dilation exceed approximately 0.5 cm per year, and/or significant aortic regurgitation is present; intermittent surveillance of the entire aorta with CT or MRA scans beginning in young adulthood or after aortic root surgery in childhood. Agents/circumstances to avoid: Contact sports, competitive sports, and isometric exercise; activities that cause joint injury or pain; agents that stimulate the cardiovascular system, including decongestants and excessive caffeine; agents that cause vasoconstriction, including triptans; LASIK correction of refractive errors; breathing against resistance or positive pressure ventilation in those with a documented predisposition for pneumothorax. Evaluation of relatives at risk: It is recommended that the genetic status of at-risk relatives be clarified so that affected individuals can undergo routine surveillance for early detection of medically significant complications, particularly potentially life-threatening cardiac manifestations. Genetic status of at-risk relatives can be established EITHER: By molecular genetic testing if the FBN1 pathogenic variant in the family is known; OR In those with a rigorously defined family history of Marfan syndrome, by the presence of ONE OR MORE of the following: Ectopia lentis. A systemic score ≥7. Aortic root dilatation (Z-score ≥2.0 for individuals age ≥20 years or Z-score ≥3.0 for those age <20 years). Pregnancy management: Pregnant women with Marfan syndrome should be followed by a high-risk obstetrician both during pregnancy and through the immediate postpartum period. In women with Marfan syndrome who anticipate pregnancy or become pregnant, β-blockers should be continued, but some other classes of medications such as ACE inhibitors or ARBs should be stopped because of the risk for fetal loss and birth defects. Cardiovascular imaging with echocardiography every two to three months during pregnancy to monitor aortic root size and growth is recommended. Monitoring should continue in the immediate postpartum period due to an increased risk for aortic dissection.


Marfan syndrome is inherited in an autosomal dominant manner. Approximately 75% of individuals with Marfan syndrome have an affected parent; approximately 25% have a de novo FBN1 pathogenic variant. The offspring of an individual with Marfan syndrome are at a 50% risk of inheriting the FBN1 pathogenic variant. Once the FBN1 pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis are possible.

Copyright © 1993-2019, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

Supplemental Content

Support Center