Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

aortic dilation meeting the indications for surgery

1st line – modified David's reimplantation with replacement of the aortic root and sparing of the aortic valve

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ACUTE
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aortic dilation meeting the indications for surgery
1st line – 

modified David's reimplantation with replacement of the aortic root and sparing of the aortic valve

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]​​ Surgery is indicated earlier (at aortic diameter >4.2 cm) in women of reproductive age who wish to become pregnant. In women who are pregnant, there is a risk of dissection when the aortic root is ≥4.2 cm.[48] 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] 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 American Heart Association and American College of Cardiology recommend that surgery to replace the aortic root and ascending aorta may be reasonable if performed by an experienced team.[19]

Surgery 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 less than 1%.[49][50]

Plus – endocarditis prophylaxis prior to high-risk procedures

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ACUTE
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aortic dilation meeting the indications for surgery
Plus – 

endocarditis prophylaxis prior to high-risk procedures

Treatment recommended for ALL patients in selected patient group

Guidelines recommend that any patient who has prosthetic material, either valve or graft, will require antibiotic prophylaxis, for invasive procedures directed against oral streptococci.[51][52]

Administered in a single dose 30 to 60 minutes prior to all dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of oral mucosa; invasive procedures of the respiratory tract that involve incision or biopsy of the respiratory mucosa; procedures on infected skin/skin structures/musculoskeletal tissue.

Cephalosporins should not be used in people with a history of anaphylaxis, angio-oedema, or urticaria with penicillins or ampicillin. 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]

2nd line – replacement of the aortic root with a composite Dacron graft and mechanical valve

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ACUTE
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aortic dilation meeting the indications for surgery
2nd line – 

replacement of the aortic root with a composite Dacron graft and mechanical valve

This procedure is now only indicated outside the centres performing modified David's aortic valve reimplantation, as it carries a higher risk of postoperative complications, such as graft infection, endocarditis or stroke, valve thrombosis, and bleeding from a lifetime of anticoagulation with warfarin.

Plus – lifelong postoperative anticoagulation

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ACUTE
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aortic dilation meeting the indications for surgery
Plus – 

lifelong postoperative anticoagulation

Treatment recommended for ALL patients in selected patient group

Patients with mechanical valves will need lifelong warfarin therapy.[52]

Factors that increase risk of major bleeding with warfarin include high-intensity anticoagulation (INR >4.0), age more than 65 years, highly variable INR, history of GI bleed, hypertension, cerebrovascular disease, serious heart disease, anaemia, malignancy, trauma, renal insufficiency, concomitant drugs, and long duration of warfarin therapy.

Primary options

warfarin: children: consult specialist for guidance on dose; adults: 2-10 mg orally once daily initially, adjust dose according to target INR

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Plus – endocarditis prophylaxis prior to high-risk procedures

Back
ACUTE
|
aortic dilation meeting the indications for surgery
Plus – 

endocarditis prophylaxis prior to high-risk procedures

Treatment recommended for ALL patients in selected patient group

Guidelines recommend that any patient who has prosthetic material, either valve or graft, will require antibiotic prophylaxis for invasive procedures, directed against oral streptococci.[51][52]

Administered in a single dose 30 to 60 minutes prior to all dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of oral mucosa; invasive procedures of the respiratory tract that involve incision or biopsy of the respiratory mucosa; procedures on infected skin/skin structures/musculoskeletal tissue.

Cephalosporins should not be used in people with a history of anaphylaxis, angio-oedema, or urticaria with penicillins or ampicillin. 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]

3rd line – root remodelling operation

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ACUTE
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aortic dilation meeting the indications for surgery
3rd line – 

root remodelling operation

This procedure has also been shown to have worse results than the David's reimplantation operation.

Plus – endocarditis prophylaxis prior to high-risk procedures

Back
ACUTE
|
aortic dilation meeting the indications for surgery
Plus – 

endocarditis prophylaxis prior to high-risk procedures

Treatment recommended for ALL patients in selected patient group

Guidelines recommend that any patient who has prosthetic material, either valve or graft, will require antibiotic prophylaxis for invasive procedures, directed against oral streptococci.[51][52]

Administered in a single dose 30 to 60 minutes prior to all dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of oral mucosa; invasive procedures of the respiratory tract that involve incision or biopsy of the respiratory mucosa; procedures on infected skin/skin structures/musculoskeletal tissue.

Cephalosporins should not be used in people with a history of anaphylaxis, angio-oedema, or urticaria with penicillins or ampicillin. 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]

retinal tear

1st line – argon laser photocoagulation, transconjunctival cryocoagulation

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ACUTE
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retinal tear
1st line – 

argon laser photocoagulation, transconjunctival cryocoagulation

Retinal tears can be repaired by argon laser photocoagulation and/or transconjunctival cryocoagulation.

retinal detachment

1st line – surgical repair

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ACUTE
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retinal detachment
1st line – 

surgical repair

Retinal detachment requires surgery. The surgical options scleral buckling, vitrectomy, or both depend on the complexity of the detachment, the status of the lens, and the severity of dislocation.

Currently available vitreoretinal techniques result in successful reattachment of the retina in >80% of the eyes.[71][72]

Retinal detachment occurs rarely in Marfan syndrome as a primary ocular event, but occurs more often as a result of vitreolensectomy.[71][72][73]

ONGOING

aortic dilation not meeting indications for surgery or following aortic surgery

1st line – beta-blocker and/or angiotensin-II receptor antagonist

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ONGOING
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aortic dilation not meeting indications for surgery or following aortic surgery
1st line – 

beta-blocker and/or angiotensin-II receptor antagonist

Beta-blockers (e.g., metoprolol, atenolol, bisoprolol) 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 (e.g., irbesartan, losartan) 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. Using cardioselective beta-blockers (e.g., metoprolol, atenolol, bisoprolol) 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 an 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.[19][44]

The AHA/ACC 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]

Primary options

metoprolol: children: consult specialist for guidance on dose; adults: 25 mg orally (extended-release) once daily initially, increase gradually according to response, maximum 400 mg/day

OR

atenolol: children: consult specialist for guidance on dose; adults: 25-50 mg orally once daily initially, increase gradually according to response, maximum 100 mg/day

OR

bisoprolol: adults: 1.25 mg orally once daily initially, increase gradually according to response, maximum 20 mg/day

OR

losartan: children: consult specialist for guidance on dose; adults: 25-50 mg orally once daily initially, increase gradually according to response, maximum 100 mg/day

OR

irbesartan: children: consult specialist for guidance on dose; adults: 75-150 mg orally once daily initially, increase gradually according to response, maximum 300 mg/day

Secondary options

metoprolol: children: consult specialist for guidance on dose; adults: 25 mg orally (extended-release) once daily initially, increase gradually according to response, maximum 400 mg/day

or

atenolol: children: consult specialist for guidance on dose; adults: 25-50 mg orally once daily initially, increase gradually according to response, maximum 100 mg/day

or

bisoprolol: adults: 1.25 mg orally once daily initially, increase gradually according to response, maximum 20 mg/day

-- AND --

losartan: children: consult specialist for guidance on dose; adults: 25-50 mg orally once daily initially, increase gradually according to response, maximum 100 mg/day

or

irbesartan: children: consult specialist for guidance on dose; adults: 75-150 mg orally once daily initially, increase gradually according to response, maximum 300 mg/day

myopia

1st line – corrective lens

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ONGOING
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myopia
1st line – 

corrective lens

Treatment may be achieved by concave spherical correction with spectacles or contact lenses. If present, astigmatism should also be corrected.

2nd line – surgery

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ONGOING
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myopia
2nd line – 

surgery

Surgery (clear lens extraction and intra-ocular lens implantation) may be performed when spectacles or contact lenses are insufficient and/or not tolerated.[74]

Young children are at risk for amblyopia and require refraction and close monitoring.[3][57]

lens subluxation/dislocation

1st line – spectacles/contact lenses

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ONGOING
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lens subluxation/dislocation
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optical correction possible, no anterior lens dislocation, no dislocation into vitreous cavity
1st line – 

spectacles/contact lenses

Lens subluxation/dislocation may cause visual symptoms that vary in severity depending on the degree of lens displacement.

If the subluxation is mild, the patient sees through the phakic portion of the pupil. Optical correction with spectacles or contact lenses is indicated as first-line treatment when possible.

If the subluxation is large enough, the patient sees through the aphakic portion of the pupil.

1st line – surgery

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ONGOING
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lens subluxation/dislocation
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optical correction not possible, anterior lens dislocation with secondary glaucoma or dislocation into vitreous cavity
1st line – 

surgery

Lens extraction and intra-ocular lens implantation is indicated if the edge of the lens bisects the pupil and optical correction is impossible.

Anterior dislocation of the lens with secondary glaucoma is an indication for lens extraction and primary or secondary intra-ocular lens implantation. Pars plana vitreolensectomy is another therapeutic option in this case.[73] Pars plana vitrectomy is also indicated when there is lens dislocation into the vitreous cavity.

Contact lenses can be tried before or after lens removal and, if tolerated, may be sufficient to correct vision without implantation of an intra-ocular lens.[58]

When an intra-ocular lens implantation is required, posterior chamber lenses are recommended because they reduce the complications of lens decentration. These lenses are sutured in place by scleral and/or iris fixation.[23][75] Lenses may be placed in the anterior chamber.[58]

cataract

1st line – surgical removal of lens, with or without intra-ocular lens implantation

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ONGOING
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cataract
1st line – 

surgical removal of lens, with or without intra-ocular lens implantation

Complications related to cataract surgery are higher in patients with Marfan syndrome compared with the general population, due to zonular weakness. The risk of posterior capsule rupture with vitreous loss and intra-ocular lens luxation into the vitreous is thus increased. The use of capsular tension rings intra-operatively reduces these complications.

scoliosis/kyphoscoliosis

1st line – orthopaedic bracing

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ONGOING
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scoliosis/kyphoscoliosis
1st line – 

orthopaedic bracing

Scoliosis and kyphoscoliosis are frequently seen in growing teenagers. Curves of 20 to 40 degrees require orthopaedic bracing, to be worn for about 23 hours a day.

2nd line – surgery

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ONGOING
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scoliosis/kyphoscoliosis
2nd line – 

surgery

Scoliosis and kyphoscoliosis are frequently seen in growing teenagers. Curves of more than 40 degrees require surgical correction with Harrington rods and spinal fusion, or telescopic magnetic growth rods, which are becoming increasingly popular for young children.[55][76][77]

severe pectus excavatum/carinatum with evidence of cardiopulmonary compromise

1st line – surgery

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ONGOING
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severe pectus excavatum/carinatum with evidence of cardiopulmonary compromise
1st line – 

surgery

Requires surgical correction if impairing breathing. Deformed sternum and ribs are straightened using a metal bar.[78] Surgery is not usually indicated for cosmetic reasons because of potential risks. If open heart surgery is required, this should be performed prior to sternal correction if possible.

1st line – brace suction or compression

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ONGOING
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severe pectus excavatum/carinatum with evidence of cardiopulmonary compromise
1st line – 

brace suction or compression

If presenting during the active growth period, may be treated by brace suction or compression.[79]

arthropathy and/or spondylolisthesis

1st line – physiotherapy and analgesics

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ONGOING
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arthropathy and/or spondylolisthesis
1st line – 

physiotherapy and analgesics

Spondylolisthesis or dural ectasia may result in low back pain. Mild arthritic pain is managed medically and with physiotherapy. Spondylolisthesis <30 degrees may also be treated with bracing, whereas a larger slippage will need surgery.

Mild painkillers (e.g., paracetamol, ibuprofen) and orthopaedic footwear may be given in cases of painful flat feet, with foot surgery only rarely becoming necessary.

Non-steroidal anti-inflammatory drugs (NSAIDs) can be taken concurrently with warfarin, if both are taken regularly, and warfarin dose is adjusted to maintain INR.

Omeprazole can be added to NSAID therapy to prevent NSAID-induced ulcers; however, it can prolong the elimination of warfarin and increase INR.

Primary options

paracetamol: children: 10-15 mg/kg orally every 4-6 hours when required, maximum 75 mg/kg/day; adults: 500-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

OR

ibuprofen: children: 5-10 mg/kg orally every 6-8 hours when required, maximum 40 mg/kg/day; adults: 400 mg orally every 4-6 hours when required, maximum 2400 mg/day

or

naproxen: adults: 250-500 mg orally twice daily when required, maximum 1250 mg/day

More

or

diclofenac potassium: adults: 50 mg orally (immediate-release) three times daily when required, maximum 150 mg/day

or

indometacin: adults: 25-50 mg orally (immediate-release) two to three times daily when required, maximum 200 mg/day

-- AND --

omeprazole: children: consult specialist for guidance on dose; adults: 10-20 mg orally once daily

2nd line – surgery

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ONGOING
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arthropathy and/or spondylolisthesis
2nd line – 

surgery

Rarely required. Refer to an orthopaedic consultant for advice and treatment. Spondylolisthesis >30 degrees will need surgical realignment. Advanced arthritis in adults due to protrusio acetabulae may necessitate hip replacement.

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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