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Clinical features

Marfan syndrome is a complex multi-systemic condition. The cardinal features are cardiovascular, skeletal 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, leading to dilatation, regurgitation and 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 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) is typically 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, resulting in features that overlap with other connective tissue conditions such as the more common (and benign) joint hypermobility syndromes.

Ocular findings

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

Other features

Patients with Marfan syndrome can be predisposed to spontaneous pneumothorax. Recurrent herniae, joint hypermobility, 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.

Genetics

Most patients with Marfan syndrome have a pathogenic or likely pathogenic variant in the FBN1 gene, which encodes the connective tissue protein fibrillin 1.

Inheritance and genomic counselling

Marfan syndrome is an autosomal dominant condition, which means that affected individuals have a 50% chance of passing the condition on to each of their children. However, the severity of the condition may vary between individuals in the same family.

In total, 25% of disease-causing variants occur de novo (they occur spontaneously in the 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 constitutional (germline) mosaicism.

Individuals with a Marfan diagnosis should be referred to clinical genetics to discuss the family implications, cascade predictive testing and reproductive options if appropriate. As there are screening and management options, children should also be referred to discuss predictive testing.

Management

The 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, 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.

At diagnosis, a baseline ophthalmic examination, echocardiogram and CT or MRI of the aorta should be performed. 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) may reduce progression of aortic dilatation in Marfan syndrome and should be considered in all patients, including children. Elective aortic root replacement surgery should also be considered, depending on aortic root measurements and other risk factors.

Patients with Marfan syndrome should be advised to avoid activities that significantly increase the risk of aortic dissection (particularly contact sports and isometric exercise), and patients considering competitive sport should discuss it with a specialist.

Patients with Marfan syndrome who are pregnant or considering pregnancy should have preconceptual counselling. They should be advised regarding cardiovascular risk, teratogenic medications (such as ACE inhibitors, warfarin and ARBS) and alternatives, as well as the option of preimplantation genetic testing where relevant. These options all require close monitoring in a specialist maternal cardiac service during pregnancy and the post-partum period.

Resources

For clinicians

References:

For patients

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  • Last reviewed: 16/03/2024
  • Next review due: 16/03/2026
  • Authors: Dr Mihir Sanghvi
  • Reviewers: Dr Makaela Jacobs-Pearson, Dr Katherine von Klemperer, Dr Phil Ostrowski