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Conditions

Marfan syndrome

Marfan syndrome is one of the most common heritable connective tissue conditions, with an estimated prevalence of approximately 1 in 5,000. It is an autosomal dominant condition resulting from disease-causing (pathogenic or likely pathogenic) variants in the fibrillin 1 gene (FBN1). Untreated Marfan syndrome is associated with a significant risk of morbidity and mortality, but appropriate surveillance and management can result in a near-normal life expectancy. 

Overview

Marfan syndrome is a syndromic condition of the connective tissue caused by deleterious variants in the FBN1 gene encoding the structural protein fibrillin-1 present in the extra-cellular matrix. Symptoms and features of Marfan syndrome are significantly variable between individuals, including between those within the same family. It affects many different body systems but most importantly, individuals may develop aortic disease, skeletal manifestations and ocular conditions. Inheritance of the condition follows an autosomal dominant pattern, with approximately 25% of cases being de novo (that is, the variant occurs for the first time in the affected individual).

Clinical features

Marfan syndrome is a complex multi-systemic condition. The cardinal features are cardiovascular, musculoskeletal and ocular disease, but there is significant variability and not all affected individuals will have the full range of features.

Cardiovascular disease

Pathology of the aortic root, namely dilatation resulting in aortic valve regurgitation and/or aortic dissection, is the main cause of morbidity and mortality in Marfan syndrome. Importantly, severity of cardiovascular manifestations exhibit poor correlation with ocular or skeletal manifestations. Rarely, sudden cardiac death can be the first presentation of the condition. Echocardiography and CT or MRI should be used regularly to assess and monitor the aorta. Mitral valve prolapse is also a common feature.

Skeletal manifestations

Individuals with Marfan syndrome are often taller than their predicted height, with disproportionately long limbs resulting in an increased arm span (height ratio >1.05). Arachnodactyly (long, slender fingers) may be present. Other skeletal and skin findings include pectus malformations, scoliosis and/or kyphosis, reduced elbow extension, excessive skin striae and hindfoot malformation or pes planus. Generalised joint hypermobility may occur, which is also seen in other connective tissue conditions such as Ehlers-Danlos syndromes and Loeys-Dietz syndrome.

Ocular findings

Ectopia lentis (lens dislocation) is the most specific ocular pathology associated with Marfan syndrome. Other ocular features include high myopia (short-sightedness), glaucoma, cataracts and atraumatic retinal detachment.

Other features

Patients with Marfan syndrome may present with spontaneous pneumothorax. Recurrent herniae, dental crowding and a high-arched palate may occur, but it should be noted that these features are considered non-specific for Marfan syndrome. Dural ectasia (the widening of the dural sac surrounding the spinal cord) usually occurs in the lumbosacral region and can cause chronic back pain.

Genomics

Most patients with Marfan syndrome have a pathogenic or likely pathogenic variant in the FBN1 gene, which encodes the connective tissue protein fibrillin 1. Fibrillin 1 is one of the components of microfibrils which form part of the network that provides strength and flexibility to connective tissue, as well as interacting with growth factors. The presence of a deleterious FBN1 variant results in decreased or dysfunctional fibrillin 1. This results in elastic fibre fragmentation and decreased tissue integrity, as well as excessive signalling of transforming growth factor-beta (TGF-beta). This results in structural weakening of the aorta, as well as tissue instability and overgrowth.

Diagnosis

Diagnosis of Marfan syndrome is most commonly made using the 2010 revised Ghent criteria. These are based on the presence or absence of family history, physical examination findings (systemic score can be calculated using this score chart), aortic root measurements and results of genomic testing (if appropriate). Genomic testing should be considered following assessment by a clinical geneticist or a clinician with expertise in aortopathies. For information about testing, see Patient with a thoracic aortic aneurysm or dissection.

Inheritance and genomic counselling

Marfan syndrome is an autosomal dominant condition.

  • Individuals affected by an autosomal dominant condition have one working copy of the gene, and one with a pathogenic variant.
  • The chance of a child inheriting the gene with the variant from an affected parent is 1 in 2 (50%).
  • Incomplete penetrance can occur (that is, not everyone who has the variant develops the disease).
  • The severity of the condition may vary between individuals within the same family.

In total, 25% of disease-causing variants occur de novo (that is, they occur spontaneously in the affected individual for the first time, rather than being inherited). If the FBN1 variant appears de novo, there is a small possibility of two unaffected parents having a second affected child due to germline mosaicism.

Individuals with a Marfan syndrome diagnosis should be referred to clinical genetics or an inherited cardiac conditions service to discuss the family implications, cascade predictive testing and reproductive options if appropriate. Female patients should be monitored carefully if embarking on a pregnancy. As there are screening and management options, children should also be referred to discuss predictive testing.

If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.

Management

Medical and surgical management of Marfan syndrome requires multi-disciplinary care – for example, clinical genetics, cardiology, cardiothoracics, ophthalmology, vascular surgery, respiratory and possibly rheumatology. At diagnosis, a baseline ophthalmic examination, echocardiogram and CT or MRI of the aorta should be performed, and other investigations could be performed on the basis of symptoms and physical findings (for example, scoliosis). Monitoring of the aorta following the baseline assessment should be repeated at regular intervals as dictated by aortic measurements – usually yearly.

Beta blockers and angiotensin II receptor blockers (ARBs) have been shown to reduce progression of aortic dilatation in Marfan syndrome and should be considered in all patients, including children. Elective aortic root replacement surgery or personalised external aortic root support (PEARS) may need to be considered, depending on aortic root measurements and other risk factors.

Lifestyle factors should also be discussed – for example, safter physical activities and the avoidance of activities that significantly increase the risk of aortic dissection (particularly contact sports and isometric exercises). Patients considering competitive sport should discuss it with a specialist. However, it is important for patients to participate in physical activity to maintain cardiovascular fitness and overall general health. Self-advocacy, emergency preparedness (for example, seeking medical advice early and carrying documentation regarding their rare genetic diagnosis) are also important discussion points.

Patients with Marfan syndrome should ideally have preconceptual counselling at the point of considering pregnancy to be advised regarding cardiovascular risk, teratogenic medications (such as ACE inhibitors, warfarin and ARBs) and alternatives, as well as the option of prenatal testing or preimplantation genetic testing where relevant. These options all require close monitoring in a specialist maternal cardiac service during pregnancy and the post-partum period, with increased surveillance with imaging.

Resources

For clinicians

References:

For patients

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  • Last reviewed: 03/06/2026
  • Next review due: 03/06/2029
  • Authors: Dr Mihir Sanghvi
  • Reviewers: Dr Neeti Ghali, Dr Makaela Jacobs-Pearson, Dr Katherine von Klemperer, Dr Phil Ostrowski