Approach

No curative treatment exists, so management aims to prevent cardiac, ophthalmic, and musculoskeletal complications, and will vary with individual symptoms.​[3][38]

Aortic dilation

Aortic dilation, dissection, and rupture all occur in people with Marfan syndrome. All patients with a Marfan syndrome diagnosis should be followed by a cardiologist with expertise in this area.[3] Aortic dissection and rupture are considered as complications of the syndrome, whereas aortic dilation is considered part of the syndrome.

Beta-blockers are an established treatment for Marfan syndrome as they reduce heart rate and myocardial contractility, and slow aortic root growth, reducing the risk of complications such as aortic dissection and rupture.[19][39][40]​​​[41]​​​ 

More recently, angiotensin-II receptor antagonists have been found to be efficacious in Marfan syndrome.[19] Approximately 20% of children with Marfan syndrome have asthma, and in these children beta-blockers are relatively contraindicated due to a risk of bronchospasm. Using cardioselective beta-blockers is likely to reduce this risk.[42]​ An angiotensin-II receptor antagonist may be used in these patients instead.[43] 

The American Academy of Pediatrics recommends treatment with either a beta-blocker or an angiotensin-II receptor antagonist in patients with Marfan syndrome and aortic root dilatation, with consideration of combination treatment where there is severe and/or progressive aortic root dilatation.[3] The American Heart Association/American College of Cardiology (AHA/ACC) also recommends either treatment option and suggests combination therapy is reasonable to reduce the rate of aortic dilation citing a meta-analysis which confirmed slower aortic growth rates with combination therapy.[19][44]​​​​​

Elective surgery is recommended once aortic diameter measures 4.5 to 5.0 cm (earlier in symptomatic patients with chest pain).[19][45][46][47]​ ​​​The measurement of the aortic root/body height ratio is taken into account in children and if this ratio is >10, elective surgery is likely, but the decision of exactly when to operate may vary between surgeons and needs to be performed by experienced surgeons as part of a multidisciplinary aortic team.[19] Surgery is indicated earlier (at aortic diameter >4.2 cm) in women of reproductive age. In women who are pregnant, there is a significant risk of dissection when the aortic root is ≥4.2 cm.[48]

In patients with an aortic diameter approaching surgical threshold, who are candidates for valve-sparing root replacement and have a very low surgical risk, the AHA and ACC recommend that surgery to replace the aortic root and ascending aorta may be reasonable if performed by an experienced team.[19] Modified David's reimplantation with replacement of the aortic root and sparing of the aortic valve has a 91% to 97% freedom from reoperation at 10 years if performed at a centre with sufficient experience and a low postoperative death rate after elective procedure <1%.[49][50]​​​ A second-line surgical option is replacement of the aortic root with a composite Dacron graft and mechanical valve, but this is now only indicated outside the centres performing modified David's aortic valve reimplantation. Lastly, the root remodelling operation has been found to have worse results than the David's reimplantation operation.

Following surgery for severe aortic dilation, lifelong therapy with beta-blockers (or an angiotensin-II receptor antagonist if beta-blockers are contraindicated/not tolerated) is indicated. Patients with mechanical valves will need lifelong warfarin therapy, and any patient who has prosthetic material, either valve or graft, will require antibiotic prophylaxis for dental work and any future invasive procedures.[51][52]

The UK National Institute for Health and Care Excellence updated their guidance in 2015, changing their recommendations from advising against, to supporting the use of, antibiotic prophylaxis in people undergoing dental procedures and procedures involving the upper and lower gastrointestinal tract, the genitourinary tract and the respiratory tract.[53] This was in response to an increased incidence of infective endocarditis in England between 2000 and 2013.[54]

Musculoskeletal findings and dural ectasia

Musculoskeletal concerns are often the presenting feature of patients with Marfan syndrome.[3] Scoliosis and kyphoscoliosis are frequently seen in growing teenagers. Curves of 20 to 40 degrees will require orthopaedic bracing, and for larger curves, surgical correction with Harrington rods and spinal fusion is required. Telescopic rods are becoming increasingly popular for young children.[55] Spondylolisthesis <30 degrees is also treated with bracing, whereas a larger slippage will require surgical realignment.

Pectus excavatum and carinatum are usually corrected surgically only if there is cardiopulmonary compromise. Surgery is not indicated for cosmetic reasons because of potential risks, unless serious psychological problems occur with body image. Experimental work with pressure bracing for pectus carinatum and suction for excavatum is promising.[56]

Arthritic pain is managed medically, but advanced arthritis in adults due to protrusio acetabulae may necessitate hip replacement. Mild painkillers and orthopaedic arch supports and footwear may be given in cases of painful flat feet, with foot surgery only rarely becoming necessary.

Physical and/or occupational therapy can help address joint laxity issues.[3]​ Dural ectasia is mostly asymptomatic and will only rarely need treatment, such as analgesics for lower back pain or neurosurgery should neurological symptoms occur (e.g., orthostatic headache, pain or numbness in legs).

Ophthalmology findings

The most common ocular feature is myopia, typically attributed to elongation of the globe. This often progresses rapidly during childhood.[3][23]​​​​ Refractive errors are corrected with spectacles/contact lenses or may need surgery. Young children are at risk for amblyopia and require refraction and close monitoring.[3][57]​​​ Ectopia lentis (dislocation of the lens) is treated either with spectacles/contact lenses or with surgery. Cataracts are treated by surgical removal of the lens and contact lenses if tolerated by the patient, or intra-ocular lens implantation in the posterior or anterior chamber.[58] Glaucoma requires either medicine or surgery, or a combination of both. See Open-angle glaucoma and Angle-closure glaucoma.

Retinal tears or retinal detachment require immediate attention. Argon laser photocoagulation or transconjunctival cryocoagulation is required for retinal tears, whereas surgical repair is needed in cases of retinal detachment. Unilateral retinal detachments may go unnoticed by patients, due to maintenance of vision in the unaffected eye, so routine vision assessments of each eye in isolation are recommended.[3] Affected individuals should be monitored at least annually by an ophthalmologist familiar with Marfan syndrome with slit-lamp examinations for lens subluxation and cataract formation, glaucoma, and fundus examinations for retinal tears or detachments.[3]

Pregnancy

Pregnancy is associated with an increase in aortic root size.[59][60]​​​ Reported aortic dissection rates during pregnancy range from 1.9% to 4.4%.[60][61]​​ Aortic size is a major determinant of risk, and guidelines recommend that women with aortic root diameter >45 mm avoid pregnancy.[45][62]

Angiotensin-II receptor antagonists should be stopped due to the risk of fetal harm.[3] There is a risk of fetal growth restriction with beta-blockers in pregnancy; however, they can generally be continued with close fetal growth monitoring.[3][63]​​​

Women with aortic dimensions greater than 4.0 cm are at risk for aortic complications during pregnancy and the postnatal period. Therefore, pregnancy should be delayed if possible until after definitive treatment of the aorta has been completed. Elective surgery to replace a dilated aortic root prior to a planned pregnancy in a Marfan syndrome woman, should be performed when aortic root diameter is 4.2 cm or greater, to avoid the increased risk of dissection due to hormone influence during pregnancy. The patient should be advised to wait one year after surgery before becoming pregnant.[64][65]

Those whose aorta is greater than 4.5 cm, or those who have previously had an aortic dissection or rupture, are at substantially higher risk.[3][66]​​ If already pregnant, clinicians should consider immediate aortic replacement, early delivery, or termination of the pregnancy, given the potentially severe consequences.[3][67][68]​​

The rate of spontaneous abortion has been reported as higher-than-expected in women with Marfan syndrome, although the etiology is unknown.[3][69]​ In addition, women with Marfan syndrome experience higher rates of preterm deliveries, premature rupture of membranes, and increased mortality of their offspring.[3][69][70]

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