Marfan's syndrome

The right clinical information, right where it's needed

Last updated: Jan 07, 2016

 Table of Contents
Summary 3

Basics 4

Definition 4
Epidemiology 4
Aetiology 5
Pathophysiology 5
Classification 5

Prevention 6

Screening 6
Secondary prevention 6

Diagnosis 7

Case history 7
Step-by-step diagnostic approach 7
Risk factors 8
History & examination factors 9
Diagnostic tests 11
Differential diagnosis 13
Diagnostic criteria 13

Treatment 16

Step-by-step treatment approach 16

Treatment details overview 17
Treatment options 19
Emerging 26

Follow up 27

Recommendations 27
Complications 27
Prognosis 29

Guidelines 31

Diagnostic guidelines 31
Treatment guidelines 31

References 33

Images 37

Disclaimer 38
 Summary

◊ An uncommon, autosomal dominant inherited disorder of connective tissue characterised by loss of elastic
tissue, resulting in musculoskeletal deformities, lens subluxation, aortic dissection, and root aneurysms.

◊ Multidisciplinary team of consultants confirm diagnosis and manage treatment.

◊ Dilation of aorta progressive if diameter is approximately >4.5 cm, but dilation may be delayed by beta-blockers
or verapamil. Risk of aortic dissection beyond this size or with pregnancy.

◊ Standard of elective surgical care for aortic dilation is modified David's reimplantation operation with preservation
of aortic valve leaflets and replacement of the aortic root.

◊ Acute aortic dissection requires immediate surgical repair and has reduced long-term survival.

◊ Other manifestations of Marfan's syndrome (e.g., lens subluxation and/or cataract, glaucoma, retinal detachment,
dural ectasia, scoliosis, and pulmonary complications) require treatment from appropriate medical or surgical
consultants.
 Marfan's syndrome Basics

Definition

This mainly autosomal dominant inherited disorder of connective tissue, characterised by loss of elastic tissue, affects
BASICS

numerous body systems, including the musculoskeletal, cardiovascular, neurological, and respiratory systems, and the
skin and eyes.[1] The essential simplified criteria for diagnosis are 3 out of the 4 following findings: relevant family history,
specific musculoskeletal abnormalities, ocular lens subluxation, and aortic dilation/dissection.[2] Skin striae, dural ectasia,
hernias, pneumothorax, and emphysematous bullae on CXR may also be noted.

Epidemiology

Prevalence is thought to be similar throughout the world and regardless of sex or ethnicity.[3] The incidence in the
European population is estimated to be 3 in 10,000.[4] The incidence in the US population is not accurately known, but
is estimated to be 1 in 10,000.[5] The average life expectancy used to be only 32 years but, due to early surgery, it is now
approaching that of the general population. Once aortic dissection occurs, survival is considerably reduced to between
50% and 70% at 5 years.[6] [7]

Impact of aortic dissection on patient survival

From the collection of LG Svensson, E Mendrinos, C Pournaras

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Marfan's syndrome Basics

Aetiology

Caused by mutations in the fibrillin-1 gene in 99% of classical Marfan's syndrome patients.[8] In 75% of patients, the gene

BASICS
is passed on from a parent and is autosomal dominant, although the appearance of family members and degree of
pathological features may vary. In 25% of patients the mutation occurs spontaneously and may be associated with older
paternal age.

The first fibrillin-1 gene mutation was identified in 1990.[9] However, subsequently, over 1000 different mutations have
been identified.[10]

Pathophysiology

Mutations in the fibrillin-1 gene result in the production of an abnormal fibrillin protein, leading to abnormalities in the
mechanical stability and elastic properties of connective tissue.[11] Up-regulation of C-terminal fragment of filamin-A
in dilated aortic media of Marfan's syndrome has been found.[12] This is due to cleavage by the protease calpain. Therefore,
increased calpain activity may help to explain histological alterations in the dilated aorta.

More recently, research suggests that transforming growth factor-beta is implicated in the failure of normal elastic tissue
formation.[13] [14]

Early experience from surgical treatment and histological studies has found that patients suffer from a loss of elastic
tissue in the aortic wall (medial degeneration). Frequently, particularly in association with aortic dissection, a loss of
smooth muscle cells (medial necrosis) is also noted. In addition, a diagnosis of cystic medial necrosis may be made, the
so-called cysts being fluid collections of mucin and ground substance. These abnormalities lead to a weakening of the
aortic wall with subsequent aortic dilation and potentially aortic dissection, aneurysms, and rupture. They also lead to a
reduction of the structural integrity of the skin, ligaments, eye lenses, lung airways, and the spinal dura.[13]

Classification

Type according to family history

Familial: 75% of cases; inherited as an autosomal dominant trait.

Sporadic: 25% of cases; the mutation occurs spontaneously and may be associated with older paternal age.

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 Marfan's syndrome Prevention

Screening

Genetic screening for fibrillin-1 gene mutations may be used for screening of other family members, including antenatal
diagnosis and pre-implantation genetic diagnosis.

Secondary prevention
Any patient who has prosthetic material, either valve or graft, will require antibiotic prophylaxis for invasive procedures.[32]

Patients with mechanical valves will need lifelong warfarin therapy.

Children require repeated refraction measurements to prevent amblyopia.

PREVENTION

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Marfan's syndrome Diagnosis

Case history

Case history #1
In a routine medical examination, a young man is noted to be tall with a slight scoliosis and pectus excavatum. He
had been told that he was over the 95% percentile for height as a child. The examining physician suspects the patient
of having Marfan's syndrome, and auscultation reveals a heart murmur. Echocardiography shows an enlarged aortic
root, aortic valve regurgitation, and mitral valve prolapse.

Case history #2
A man in his 40s presents in the emergency department with sudden-onset chest pain. He is noticed to be tall. The
CT scan of his chest reveals acute aortic dissection requiring immediate surgical repair.

Other presentations
Acute aortic dissection not infrequently causes sudden-onset left shoulder or abdominal pain. However, pain may be
absent altogether, especially in patients on corticosteroids. Clinical presentations related to musculoskeletal problems
(e.g., scoliosis), hernias, or ophthalmic refractive errors are less common. The main ocular symptoms are blurred vision
and monocular diplopia caused by progressive lens subluxation and resulting severe astigmatism.

Step-by-step diagnostic approach

History and physical examination (including slit-lamp ophthalmic examination with pupil dilation) in conjunction with
imaging of the aortic root and the ascending, descending, and abdominal aorta (echo, CT, MRI) are usually sufficient for
diagnosis.[1]

Use of diagnostic criteria

DIAGNOSIS
There are two main sets of diagnostic criteria in use, and there is debate among doctors over which is the most
appropriate. However, it is likely that they will be superseded by a further revision in the near future.

The essential simplified criteria for diagnosis are 3 of the 4 following findings: relevant family history; specific
musculoskeletal abnormalities (including high arched palate, pectus excavatum, flat feet, arachnodactyly with positive
thumb sign, [Fig-1] dolichostenomelia with increased arm span, and high level of pubic bone), ocular lens subluxation,
and aortic dilation/dissection.[2]

These criteria were revised in 1996 into a list of features categorised as major and minor criteria.[15] These revised
diagnostic criteria require people with a negative family history to have 2 major criteria and 1 minor criterion. People
with a positive family history (parent, sibling, or child) or documented genetic mutation in the family and in the patient,
usually fibrillin-1, require 1 major plus 1 minor criterion (see diagnostic criteria section).

Identification of risk factors

Risk factors include the presence of a family history of Marfan's syndrome, or of aortic dissection or aneurysm. There
is also a weak association with high parental age.

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 Marfan's syndrome Diagnosis
Other historical considerations
There may be a family history of myopia, astigmatism, strabismus, amblyopia, premature cataract or other lens
abnormalities, glaucoma, retinal detachment, dental extraction or braces for dental crowding, hernias, or spontaneous
pneumothorax. Patients may have a history of joint pain or low back ache.[1]

Physical examination
Tall stature, wide arm span, high level of pubic bone, high arched palate, arachnodactyly, positive wrist and thumb
sign, [Fig-1] pectus excavatum, pectus carinatum, scoliosis and striae (other than from pregnancy/weight change),
flat feet, thick spectacles for myopia, hernias, aortic or mitral valve murmur may be present. Spontaneous pneumothorax
or emphysematous bullae may present as dyspnoea. Skeletal abnormality may result in other pulmonary complications
also presenting as dyspnoea.

There may be signs of heart failure due to valve disease or cardiomyopathy.[16]

Complete ophthalmic examination, including fundus examination with pupil dilation, is recommended in all patients.
There may be signs of lens subluxation or dislocation, cataract, glaucoma, or retinal detachment.

It is possible that the patient may present with signs and symptoms of acute aortic dissection or rupture. This
presentation is covered in the complications section.

Initial investigations
Echocardiography, thorax CT, and thorax MRI are used initially for aortic root imaging. Abdominal ultrasound, CT, and
MRI are used for visualisation of the descending aorta. CXR is performed to exclude the presence of a pneumothorax,
and may reveal emphysematous bullae.

Subsequent investigations
Blood screening for mutations in the fibrillin-1 (FBN1) gene confirms the diagnosis if in doubt. Once detected, the
mutation can be used to screen other relatives, and used for antenatal diagnosis and pre-implantation genetic
diagnosis. This test is more specific than MRI for dural ectasia, which can also be found in Ehlers-Danlos syndrome.
DIAGNOSIS

Lower spine CT scan or MRI can be performed to exclude dural ectasia. This is a widening of the dural membrane
surrounding the spinal cord and is a recognised complication of Marfan's syndrome. MRI is particularly useful for
follow-up investigations to avoid accumulative radiation, assessing aortic size and extent of any dural ectasia.

Plasma homocysteine levels help in unclear cases to differentiate homocystinuria. A skin biopsy is indicated only if
Ehlers-Danlos syndrome is suspected.

Risk factors
Strong
FHx of Marfan's syndrome
• Inherited as an autosomal dominant condition in 75% of cases.
• 50% risk of a child having Marfan's syndrome if one parent is affected.

FHx of aortic dissection or aneurysm

• Regular monitoring is recommended for family members at risk.

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Marfan's syndrome Diagnosis
Weak
high parental age
• Associated with spontaneous gene mutations, including those resulting in Marfan's syndrome.

History & examination factors

Key diagnostic factors

presence of risk factors (common)

• Risk factors include the presence of a family history of Marfan's syndrome, or of aortic dissection or aneurysm.
There is also a weak association with high parental age.

tall stature (common)

• Typically associated with dolichostenomelia (unusually long limbs).

wide arm span (common)

• Arm span-to-height ratio >1.05.

high level of pubic bone (common)

• Pubic bone-to-height ratio >0.5.

high arched palate (common)

• May lead to dental crowding.

arachnodactyly (common)
• Long, slender fingers are a characteristic finding.

positive wrist sign (common)

DIAGNOSIS
• Distal phalanges of the first and fifth digits of the hand overlap when wrapped around the other wrist.

positive thumb sign (common)

• When the patient bends the thumb toward the palm of the hand and covers it with the fingers, the tip of the thumb
protrudes beyond the palm of the clenched hand. [Fig-1]

pectus excavatum (funnel chest) (common)

• Sternum sunk inwards.

pectus carinatum (pigeon breast) (common)

• Sternum pushed outwards.

scoliosis (common)
• Most commonly develops in childhood and adolescence with rapid growth.
• Can affect any part of the spine and varies in severity and need for treatment.

flat feet (pes planus) (common)

• Due to ligament laxity.

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 Marfan's syndrome Diagnosis
dislocated/subluxed eye lens (common)
• Systematic investigation required if this diagnosis is considered.
• Between 50% and 80% of patients have some degree of lens subluxation, which is usually bilateral and symmetrical.
• The direction of dislocation/subluxation is typically superotemporal, whereas dislocation into the vitreous cavity
or the anterior chamber is rare.
• Other less frequent lens abnormalities are microspherakia and lens coloboma.[17]

myopia and/or astigmatism (common)

• Refraction and ocular motility are performed as part of a thorough ophthalmic assessment with full pupil dilation.
• Most people with Marfan's syndrome are myopic and astigmatic.
• Anisometropia, amblyopia, or strabismus may occur.
• Children require screening for amblyopia.

retinal abnormalities (common)

• Fundus examination is an important part of a thorough ophthalmic examination.
• Retinal abnormalities include myopic posterior staphyloma, lattice degeneration, white-without-pressure, retinal
pigmentary changes, atrophic holes or retinal tears, choroidal and scleral thinning.
• The most serious complication is retinal detachment, which may be bilateral.[17]

joint hypermobility (common)

• Incidence of joint dislocation (apart from the patella) similar to that in the general population.

aortic valve murmur (common)

• Present in about one third of adults.

mitral valve murmur (common)

• Approximately one third of people have a non-ejection systolic click and about 10% have a regurgitation murmur.

hx of treatment for dental crowding (common)

DIAGNOSIS

• Dental extraction or braces for dental crowding is a common requirement in people with Marfan's syndrome, due
to narrow jaw and high arched palate.

hx of myopia and/or astigmatism (common)

• There may also be a history of other eye problems including strabismus, lens dislocation, cataract, glaucoma, or
retinal detachment.

reduced elbow extension (uncommon)

• Extension of <170 degrees is 1 of the major skeletal features.[15]

Other diagnostic factors

glaucoma (common)
• Primary open-angle glaucoma is the most prevalent form of glaucoma in these patients.
• Secondary open-angle glaucoma may occur following chronic iritis.
• Primary angle closure glaucoma has not been described in Marfan's syndrome.
• Pupillary block is rare and can be produced by an anterior lens dislocation.
• Secondary angle closure may occur and is associated with congenital abnormalities of the irido-corneal angle.[17]

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Marfan's syndrome Diagnosis
hx of spontaneous pneumothorax (common)
• May be recurrent.

striae (common)
• Unrelated to pregnancy/weight change (usually on shoulder, lumbar area to mid-back, thighs, and around knees).

low back ache (common)

• Suggestive of spondylolisthesis or dural ectasia.

joint pain (common)

• Suggestive of arthritis.
• Hips: due to protrusio acetabulae (adults).
• Other joints: due to hypermobility.

inguinal/abdominal/incisional hernias (common)

• May be recurrent.

dyspnoea (uncommon)
• Restrictive lung disease may be due to skeletal deformity.
• May also be related to development of emphysematous bullae, spontaneous pneumothorax, fibrosis, or asthma.

signs of heart failure (uncommon)

• Due to heart valve disease or cardiomyopathy.

Diagnostic tests
1st test to order

Test Result

DIAGNOSIS
echocardiography aortic regurgitation; aortic root
dilation or ascending aortic
• If aortic dissection is found, there may potentially be rupture or leak.
dissection; mitral valve
• Mitral valve regurgitation and/or calcification may occur.
prolapse

CT scan, thorax aortic root dilation or ascending

aortic dissection; aortic
• If aortic dissection is found, there may potentially be rupture or leak.
• Mitral valve regurgitation and/or calcification may occur. regurgitation; mitral valve
prolapse

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 Marfan's syndrome Diagnosis

Test Result
slit-lamp eye examination with intra-ocular pressure measurement visualisation of
subluxed/dislocated lens or
• As part of a thorough ophthalmic assessment with full pupil dilation.
other lens abnormalities (e.g.,
microspherakia, lens coloboma
or lens opacities); elevated
intra-ocular pressure; other
anterior segment findings (e.g.,
megalocornea or cornea plana,
corneal endothelial guttata, iris
coloboma, eccentric and poorly
pharmacologically dilated
pupils)

ultrasound, abdomen aortic dissection of descending

aorta or abdominal aneurysm
• Useful for visualisation of the descending aorta.
CXR pneumothorax, apical blebs;
• Helpful to exclude spontaneous pneumothorax and reveal pulmonary changes. enlargement of the aortic and
cardiac silhouette in thoracic
dissection

MRI, thorax aortic root dilation or ascending

aortic dissection, potentially
• Particularly useful for follow-up to avoid accumulative radiation.
with rupture or leak; aortic
regurgitation; mitral valve
prolapse/regurgitation/calcification

CT scan, abdomen aortic dissection of descending

aorta or abdominal aneurysm
• Used to examine the descending and abdominal aorta.
MRI, abdomen aortic dissection of descending
aorta or abdominal aneurysm
• Used to examine the descending and abdominal aorta.

Other tests to consider

DIAGNOSIS

Test Result
CT scan, lower spine dural ectasia: widening or
ballooning of dural sac
• May be used to exclude dural ectasia.
blood screening for fibrillin-1 (FBN1) gene mutation mutations in FBN-1 gene
• Positive for mutation in 92% of classical Marfan's syndrome patients.[8]
• Interpretation of results must be done in correlation with information gathered
from accurate clinical examination.
MRI, lower spine dural ectasia: widening or
ballooning of dural sac
• Patient should stand upright during investigation.
skin biopsy no changes consistent with
• Only indicated if Ehlers-Danlos syndrome is suspected and requires exclusion. Ehlers-Danlos syndrome
plasma homocysteine levels not elevated
• Indicated if diagnosis is not clear and homocystinuria is suspected.

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Marfan's syndrome Diagnosis

Differential diagnosis

Condition Differentiating signs / Differentiating tests

symptoms
Aortic dissection not • No eye or musculoskeletal • Mutation screening for thoracic
associated with Marfan's findings. aortic aneurysm and dissection
syndrome • Relevant family history in familial genes TGFBR1/TGFBR2,[18]
dissections. ACTA2,[19] MYH11,[20]
SMAD3,[21] and TGFB2.[22] [23]

Bicuspid aortic valve • No eye or musculoskeletal • Echo, thorax CT, or thorax MRI will
findings, although occasionally show abnormal bicuspid aortic
occurs with Marfan's syndrome. valve.

Ehlers-Danlos syndrome • Joint hypermobility more • Skin biopsy for abnormal collagen
common presentation. and DNA testing for gene
• Type IV variety, which most mutation.
commonly affects the aorta, is
characterised by thin skin and
bleeding disorders with increased
bruising.

Erdheim's deformity • Flask-like root dilation of the • No differentiating tests.

aortic root as in Marfan's
syndrome, but no eye or
musculoskeletal findings or family
history.

Homocystinuria • Signs and symptoms very similar. • Plasma homocysteine levels are
• Generalised osteoporosis and elevated.
disorders of mental development
more likely in homocystinuria.

Loeys-Dietz syndrome • No associated lens dislocation. • Mutation screening for

DIAGNOSIS
• Aortic dissection occurs at much TGFBR1/TGFBR2 genes.
smaller diameter.[24]
• Bifid uvula or cleft palate.
• Arterial tortuosity.
• Hypertelorism.

XXY (Klinefelter) syndrome • No associated lens dislocation or • Karyotype reveals extra X

aortic aneurysm. chromosome.
• Mental deficiency.
• Hypogonadism.

Marfanoid hypermobility • X-linked. • No gene identified.

syndrome • No eye or heart involvement.

Diagnostic criteria

Diagnostic criteria proposed by the International Nosology of Heritable Disorders

of Connective Tissue, Berlin, 1986[2]
The presence of 3 of 4 major criteria:

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 Marfan's syndrome Diagnosis

• Family history

• Lens subluxation (ectopia lentis)

• Musculoskeletal findings

• Aortic dilation or dissection.

Revised diagnostic criteria for the Marfan syndrome[15]

Simplified as:

Negative family history: 2 major criteria and 1 minor criterion

Positive family history (parent, sibling, or child) or documented genetic mutation in family and in patient, usually fibrillin-1
gene: 1 major plus 1 minor criterion.

Major criteria:

• Aortic dilation or dissection

• Lens subluxation

• Dural ectasia

• Finding of 4 of the following musculoskeletal features: pectus excavatum, arm span/height ratio >1.05, scoliosis,
reduced elbow extension (<170 degrees), wrist sign and thumb sign, pes planus (flat feet), and protrusio acetabulae.

Minor criteria:

• Hypermobility
DIAGNOSIS

• High arched palate

• Facial appearance

• Flat cornea

• Increased axial orbit size

• Mitral valve prolapse with regurgitation

• Increased pulmonary artery size

• Calcified mitral valve <40 years

• Aortic dissection of descending aorta or abdominal aneurysm <50 years

• Pneumothorax

• Apical blebs

• Striae

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Marfan's syndrome Diagnosis

• Incisional hernia.

Revised Ghent nosology for the Marfan syndrome[25]

An international expert panel has established a revised Ghent nosology that puts more weight on the cardiovascular
manifestations (in particular, aortic root aneurysm) and ectopia lentis, which are the cardinal clinical features. The presence
of these 2 features are sufficient for the unequivocal diagnosis of Marfan's syndrome. In the absence of either of these,
the presence of a bona fide fibrillin-1 (FBN1) mutation or a combination of systemic manifestations is required. These
criteria may delay a definitive diagnosis of Marfan's syndrome, but will decrease the risk of premature diagnosis or
misdiagnosis and facilitate worldwide discussion of risk and management guidelines. Dura ectasia is no longer a major
finding as it is non-specific and also found in Ehlers-Danlos syndrome

DIAGNOSIS

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 Marfan's syndrome Treatment

Step-by-step treatment approach

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

Aortic dilation
Aortic dilation, dissection, and rupture all occur in people with Marfan's syndrome. Aortic dissection and rupture are
considered as complications of the syndrome, whereas aortic dilation is considered part of the syndrome.

In patients with aortic dilation, if the aortic root area/body height ratio is <10 or the aortic diameter is approximately
<4.5 cm (<4.0 cm in women at reproductive age), beta-blocker (or the calcium channel blocker verapamil) therapy is
instituted to prevent further aortic dilation. Beta-blockers have been shown to reduce the rate of aortic growth and
reduce the risk of complications such as aortic dissection and rupture.[26] However, 20% of children with Marfan's
syndrome have asthma, and in these children beta-blockers are contraindicated.

Elective surgery is recommended once aortic diameter measures 4.5 cm to 5 cm (earlier in symptomatic patients
with chest pain) or if aortic root area over body height ratio is >10.[27] [28] Surgery is indicated earlier (at aortic
diameter >4.2 cm) in women of reproductive age. In women who are pregnant, there is a risk of dissection when the
aortic root is ≥4.2 cm.[29] The measurement of the aortic root/body height ratio is taken into account and if this ratio
is >10, elective surgery is likely, but the decision of exactly when to operate may vary between surgeons.

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 sufficiently large experience and postoperative
death rate after elective procedure <1%.[30] [31] 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 verapamil 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.[32]

There is some early evidence to suggest that angiotensin-converting enzyme inhibitors and angiotensin-II receptor
antagonists can slow the progression of aortic dilation in Marfan's syndrome, but these treatments require further
evaluation in robust clinical trials.[26] The use of losartan (an angiotensin-II receptor antagonist) alone and in
combination with beta-blockers has shown positive results in delaying the progression of aortic dilation in preliminary
clinical trials.[33] [34] [35] Although the results of these early trials are promising, losartan is still being evaluated in
randomised placebo-controlled trials. One large trial has compared losartan with the beta-blocker atenolol in children
and young adults with Marfan's syndrome.[36] The trial found losartan and atenolol to be equally effective at reducing
aortic root dilation over 3 years. Discussion continues as to the relative merits of atenolol and losartan.[37] [38] [39]
[40] Some physicians recommend using both as complementary medications.[41] Evidence is emerging that the
patient’s response to losartan depends on the type of fibrillin-1 (FBN1) mutation.[42] More large trials are needed to
TREATMENT

establish the role of losartan in the management of Marfan's syndrome.[43]

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Marfan's syndrome Treatment
Musculoskeletal findings and dural ectasia
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.
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.

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.

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., pain or numbness in legs).

Ophthalmogy findings
Refractive errors are corrected with spectacles/contact lenses or may need surgery. Dislocation of the lens is treated
either with a combination of spectacles/contact lenses and 1% atropine drops or with surgery. Cataracts are treated
by surgical removal of the lens and intra-ocular lens implantation. Glaucoma requires either medicine or surgery, or
a combination of both (see glaucoma topics for more detail concerning specific treatment).

Retinal tears or retinal detachment need immediate attention. Argon laser photocoagulation or transconjunctival
cryocoagulation is required for retinal tears, whereas surgical repair is needed in cases of retinal detachment.

Treatment details overview

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Acute ( summary )
Patient group Tx line Treatment

aortic dilation meeting the indications for 1st modified David's reimplantation with replacement
surgery of the aortic root and sparing of the aortic valve

plus endocarditis prophylaxis prior to high-risk

procedures

2nd replacement of the aortic root with a composite

Dacron graft and mechanical valve

plus lifelong postoperative anticoagulation

plus endocarditis prophylaxis prior to high-risk

procedures
TREATMENT

3rd root remodelling operation

plus endocarditis prophylaxis prior to high-risk

procedures

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 Marfan's syndrome Treatment

Acute ( summary )
retinal tear or detachment 1st argon laser photocoagulation, transconjunctival
cryocoagulation, or surgical repair

Ongoing ( summary )
Patient group Tx line Treatment

aortic dilation not meeting indications for 1st beta-blocker

surgery or following aortic surgery

2nd angiotensin-II receptor antagonist

3rd verapamil

myopia 1st corrective lens

2nd surgery

lens subluxation/dislocation

optical correction possible, no 1st spectacles/contact lenses with or without atropine

anterior lens dislocation, no drops
dislocation into vitreous cavity

optical correction not possible, 1st surgery

anterior lens dislocation with
secondary glaucoma or
dislocation into vitreous cavity

cataract 1st surgical removal of lens and intra-ocular lens

implantation

scoliosis/kyphoscoliosis 1st orthopaedic bracing

2nd surgery

severe pectus excavatum/carinatum with 1st surgery

evidence of cardiopulmonary compromise

arthropathy and/or spondylolisthesis 1st physiotherapy and analgesics

2nd surgery
TREATMENT

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Marfan's syndrome Treatment

Treatment options

Acute
Patient group Tx line Treatment
aortic dilation meeting the indications for 1st modified David's reimplantation with replacement
surgery of the aortic root and sparing of the aortic valve
» Elective surgery is recommended once aortic
diameter measures 4.5 cm to 5 cm (earlier in
symptomatic patients with chest pain) or if aortic root
area over body height ratio is >10.[27] [28] 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.[29] The measurement
of the aortic root/body height ratio is taken into
account and if this ratio is >10, elective surgery is likely,
but the decision of exactly when to operate may vary
between surgeons. Surgery has a 91% to 97% freedom
from reoperation at 10 years if performed at a centre
with sufficiently large experience and postoperative
death rate after elective procedure less than 1%.[30]
[31]

plus endocarditis prophylaxis prior to high-risk

procedures
» Guidelines recommend that any patient who has
prosthetic material, either valve or graft, will require
antibiotic prophylaxis for invasive procedures directed
against viridans group streptococci.[32]

» 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.

2nd 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,
TREATMENT

endocarditis or stroke, valve thrombosis, and bleeding

from a lifetime of anticoagulation with warfarin.

plus lifelong postoperative anticoagulation

» Patients with mechanical valves will need lifelong
warfarin therapy.

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 Marfan's syndrome Treatment

Acute
Patient group Tx line Treatment
» 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: 5-10 mg orally once daily initially,
adjust according to INR (target: 2.5 to 3.5)

plus endocarditis prophylaxis prior to high-risk

procedures
» Guidelines recommend that any patient who has
prosthetic material, either valve or graft, will require
antibiotic prophylaxis for invasive procedures directed
against viridans group streptococci.[32]

» 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.

3rd 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
» Guidelines recommend that any patient who has
prosthetic material, either valve or graft, will require
antibiotic prophylaxis for invasive procedures directed
against viridans group streptococci.[32]

» 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
TREATMENT

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.

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Marfan's syndrome Treatment

Acute
Patient group Tx line Treatment
» Cephalosporins should not be used in people with a
history of anaphylaxis, angio-oedema, or urticaria with
penicillins or ampicillin.

retinal tear or detachment 1st argon laser photocoagulation, transconjunctival

cryocoagulation, or surgical repair
» Retinal tears can be repaired by argon laser
photocoagulation and/or transconjunctival
cryocoagulation. 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.[44] [45]

Ongoing
Patient group Tx line Treatment
aortic dilation not meeting indications for 1st beta-blocker
surgery or following aortic surgery » Treatment with beta-blockers has been shown to
reduce the rate of aortic growth and reduce the risk of
complications such as aortic dissection and
rupture.[26]

» Metoprolol is most commonly used; however, atenolol

or bisoprolol may also be used as alternative options.

» In adult patients with an aortic diameter <4.5 cm this

may prevent further significant dilation for many years.

» Special considerations and dose adjustments are

required for children. Atenolol is usually the
beta-blocker of choice in paediatric patients.

» While titrating dose to effect, avoid systolic BP <100

mmHg and heart rate much <60 beats per minute.

Primary options

» metoprolol: adults: 25 mg orally

(extended-release) once daily initially, increase
gradually according to response, maximum 200
TREATMENT

mg/day

Secondary options

» atenolol: children: consult specialist for guidance

on dose; adults: 25-100 mg orally once daily

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 Marfan's syndrome Treatment

Ongoing
Patient group Tx line Treatment
OR
» bisoprolol: adults: 1.25 mg orally once daily
initially, increase gradually according to response,
maximum 10 mg/day

2nd angiotensin-II receptor antagonist

» There is some early evidence to suggest that ACE
inhibitors and angiotensin-II receptor antagonists (e.g.,
losartan, irbesartan) can slow the progression of aortic
dilation in Marfan's syndrome, but these treatments
require further evaluation.[26] The use of losartan alone
and in combination with beta-blockers has shown
positive results in delaying the progression of aortic
dilation in preliminary clinical trials.[33] [34] [35]
Although the results of these early trials are promising,
losartan is still being evaluated in randomised
placebo-controlled trials. One large trial has compared
losartan with the beta-blocker atenolol in children and
young adults with Marfan's syndrome.[36] The trial
found losartan and atenolol to be equally effective at
reducing aortic root dilation over 3 years. Discussion
continues as to the relative merits of atenolol and
losartan.[37] [38] [39] [40] Some physicians
recommend using both as complementary
medications.[41]

» Evidence is emerging that the patient’s response to

losartan depends on the type of fibrillin-1 (FBN1)
mutation.[42] More large trials are needed to establish
the role of losartan in the management of Marfan's
syndrome.[43]

Primary options

» losartan: children: consult specialist for guidance

on dose; adults: 50-100 mg orally once daily

OR
» irbesartan: children: consult specialist for guidance
on dose; adults: 75-300 mg orally once daily

3rd verapamil
» Given if beta-blockers or angiotensin-II receptor
antagonists are contraindicated or not tolerated.

» While titrating dose to effect, avoid systolic BP <100

TREATMENT

mmHg and heart rate much <60 beats per minute.

Primary options

» verapamil: adults: 40-80 mg orally

(immediate-release) three times daily

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Marfan's syndrome Treatment

Ongoing
Patient group Tx line Treatment
myopia 1st corrective lens
» Treatment may be achieved by concave spherical
correction with spectacles or contact lenses. If present,
astigmatism should also be corrected.

2nd surgery
» Surgery (clear lens extraction and intra-ocular lens
implantation) may be performed when spectacles or
contact lenses are insufficient and/or not tolerated.[46]

lens subluxation/dislocation

optical correction possible, no 1st spectacles/contact lenses with or without atropine

anterior lens dislocation, no drops
dislocation into vitreous cavity » 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.

» Pupil dilation with atropine, and optical correction

with contact lenses, is indicated when possible.

Primary options

» atropine ophthalmic: children: (0.5%) 1-2 drops

into the affected eye(s) twice daily; adults: (1%) 1-2
drops into the affected eye(s) twice daily

optical correction not possible, 1st surgery

anterior lens dislocation with » Lens extraction and intra-ocular lens implantation is
secondary glaucoma or indicated if the edge of the lens bisects the pupil and
dislocation into vitreous cavity 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.[47] Pars plana vitrectomy is also
TREATMENT

indicated when there is lens dislocation into the

vitreous cavity.

» 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

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 Marfan's syndrome Treatment

Ongoing
Patient group Tx line Treatment
fixation.[17] [48] Lenses may be placed in the anterior
chamber.[49]

cataract 1st surgical removal of lens and intra-ocular lens

implantation
» Complications related to cataract surgery are higher
in patients with Marfan's 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 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 surgery
» Scoliosis and kyphoscoliosis are frequently seen in
growing teenagers. Curves of more than 40 degrees
will require surgical correction with Harrington rods
and spinal fusion.

severe pectus excavatum/carinatum with 1st surgery

evidence of cardiopulmonary compromise » Requires surgical correction if impairing breathing.
Deformed sternum and ribs are straightened using a
metal bar. 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.

arthropathy and/or spondylolisthesis 1st 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., acetaminophen, ibuprofen) and

TREATMENT

orthopaedic footwear may be given in cases of painful

flat feet, with foot surgery only rarely becoming
necessary.

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Marfan's syndrome Treatment

Ongoing
Patient group Tx line Treatment
» 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
Dose expressed as naproxen base.
-or-
» diclofenac: 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 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.
TREATMENT

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 Marfan's syndrome Treatment

Emerging
External stent to support aorta
The experimental procedure involves a mesh tube, custom made using computer-aided design, wrapped around the
root of the aorta. Long-term follow-up is under way to evaluate the procedure, which is available only in a few specialised
centres.[28] [50]
TREATMENT

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Marfan's syndrome Follow up

Recommendations
Monitoring

FOLLOW UP
Patients with an aortic diameter <4.5 cm or aortic root area/body height ratio <10, treated with beta-blockers or
verapamil, have a repeat echo and CT of thorax after 3 to 6 months, and then the trend is noted at yearly intervals.
MRI of the thorax is preferred for follow-up evaluation to prevent accumulative radiation.

After elective surgery and stable aortic size, a yearly echo and MRI (every 2 to 3 years) of the thorax are performed to
check the condition of the remaining aorta.

After acute dissection or surgical repair of chronic dissection, an initial check-up should be scheduled every 3 months,
then every 1 to 2 years, and include echo and MRI/CT scan of the thorax.

Patients with Marfan's syndrome also need routine eye care for optical correction of refractive errors, periodic
monitoring of intra-ocular pressure, and anterior segment examination with a slit-lamp to assess the eye for lens
location and opacities. Fundus examination with pupil dilation is routinely performed in all cases, with particular
attention to peripheral retinal changes, tears, or detachment.

Specific attention and more frequent monitoring (once every trimester) is required in pregnant women or women
planning pregnancy. These patients should also receive genetic counselling about their 50% risk of passing on their
condition to their children. Pre-pregnancy counselling should include advice regarding options of antenatal diagnosis
by chorionic villus biopsy at 11 weeks' gestation, or pre-implantation genetic diagnosis to ensure an unaffected fetus.

Patient instructions
The recommendations concerning which sports are safe in these often young patients can be difficult. Generally, the
common factor that is associated with the precipitation of acute aortic dissection is rapid upper chest movement
while straining. This may include: netball, basketball, tennis, golf, baseball, football, swinging an axe or spade,
weightlifting, and suddenly lifting something heavy. Sports that appear safe are cycling, jogging, and gentle swimming.
Contraindicated sports include heavy weightlifting and long-distance running, involving prolonged exertion at peak
capacity. After surgery, restrictions are not as strong but straining is still discouraged.

Patients are instructed to seek immediate ocular examination if they develop ophthalmological symptoms such as
the perception of floaters (myodesopsia), flashing lights (photopsia), glare, or visual-field defect.

Complications

Complications Timeframe Likelihood

coronary ostial aneurysm following aortic repair long term low

Risk dependent on method used to reattach the coronary artery button.

acute aortic dissection/rupture variable high

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 Marfan's syndrome Follow up

Complications Timeframe Likelihood

May present with: severe, stabbing, sudden-onset chest pain; absent pulses; confusion; tachycardia; loss of
FOLLOW UP

consciousness; signs of abdominal ischaemia; differing BP in different arms, wide pulse pressure due to aortic
regurgitation, or distant heart sounds secondary to tamponade.

Pain is frequently associated with rapid upper chest movement while straining (e.g., swinging an axe or spade), golf,
basketball, baseball, tennis, or lifting something heavy.

Left shoulder or abdominal pain is not infrequent.

Pain may be absent, especially in patients on corticosteroids.

Requires immediate surgery, once confirmed by echo and CT scan/MRI of the thorax. Exceptions are previous cardiac
surgery, dissection more than a few days old, history of CAD, and anticoagulation therapy.

Cardiac catheterisation is recommended in patients with previous cardiac surgery and those with possible CAD.

Acute dissection beyond the left subclavian artery is initially treated unless there is evidence of distal ischaemia.

Following surgery for aortic dissection, lifelong therapy with beta-blockers (or verapamil if beta-blockers are
contraindicated/not tolerated) is indicated.

chronic aortic dissection variable high

Usually seen after previous cardiac surgery.

Patients require extensive work-up for surgery. Most require initial aortic arch replacement beyond a previous ascending
aortic graft insertion using the so-called elephant trunk procedure.[51]

A second-stage elephant trunk procedure is required 2 to 4 months postoperatively.

In many patients, the entire aorta is replaced because of the dissected weakened aorta becoming aneurysmal.

Following surgery for aortic dissection, lifelong therapy with beta-blockers (or verapamil if beta-blockers are
contraindicated/not tolerated) is indicated.

continued aortic dilation variable medium

The weakened aortic wall is still too stressed by pulsatile flow.

If dilation is beyond 2 mm every 6 months or aortic root area/body height ratio of 10 despite drug treatment, surgical
referral is recommended.

symptomatic aortic regurgitation variable medium

Occurs with aortic root dilation.

spontaneous pneumothorax variable medium

May be recurrent.

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Marfan's syndrome Follow up

Complications Timeframe Likelihood

severe mitral regurgitation variable low

FOLLOW UP
Mitral valve prolapse often progresses to severe mitral valve regurgitation, especially in females.

Surgery is indicated when regurgitation either becomes severe (grade 4+) or symptomatic, or if there is evidence of
haemodynamic compromise.[52]

infective endocarditis variable low

Low risk in David's reimplantation; high risk in composite valve graft procedure.

heart failure variable low

Heart valve disease or intrinsic cardiomyopathy may occur and require referral to a cardiologist.

symptomatic inguinal/abdominal/incisional hernia variable low

May be recurrent.

Prognosis

The most important factors in treatment of Marfan's syndrome are the diagnosis of the condition, careful long-term
follow-up for aortic expansion, referral for surgery when the aortic root area/body height ratio reaches 10 or aortic root
diameter in the sinus of Valsalva reaches 4.5 cm to 5.0 cm, and emergency surgery for acute dissection. Long-term
survival is excellent with beta-blocker control and surgery when indicated. Acute dissection results in a reduced survival
even if successfully treated.[6] [7]

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FOLLOW UP
Marfan's syndrome Follow up

Impact of aortic dissection on patient survival

From the collection of LG Svensson, E Mendrinos, C Pournaras

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Marfan's syndrome Guidelines

Diagnostic guidelines

North America

Evaluation of the adolescent or adult with some features of Marfan syndrome

Published by: American College of Medical Genetics and Genomics Last published: 2012

Summary: This guideline provides an approach to the diagnosis of patients with features suggestive of Marfan's
syndrome.

Oceania

Recent developments in the diagnosis of Marfan syndrome and related disorders

Published by: Medical Journal of Australia Last published: 2012

GUIDELINES
Summary: This article looks at the clinical criteria for diagnosing Marfan's syndrome, comparing the original criteria
published in 1966 and the differences in the revised criteria published in 2010. The article also reviews other
developments in the understanding of Marfan's syndrome, such as DNA testing and potential therapies.

Treatment guidelines

Europe

Guidelines on the management of valvular heart disease

Published by: European Society of Cardiology Last published: 2012

Summary: Includes specific recommendations on management of valvular heart disease in patients with Marfan's
syndrome.

ESC guidelines on the management of cardiovascular diseases during pregnancy

Published by: European Society of Cardiology Last published: 2011

Summary: Includes recommendations on management of pregnancy in Marfan's syndrome.

ESC guidelines for the management of grown-up congenital heart disease

Published by: European Society of Cardiology Last published: 2010

Summary: Includes brief outline recommendations on the management of heart disease in Marfan's syndrome and
guidance on the transfer from paediatric to adult cardiology services.

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 Marfan's syndrome Guidelines

North America

Prevention of infective endocarditis

Published by: American Heart Association Last published: 2007

Summary: Endocarditis prophylaxis is indicated prior to high-risk procedures in patients with prosthetic cardiac valve
or prosthetic material used for cardiac valve repair.
GUIDELINES

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Marfan's syndrome References

Key articles

REFERENCES
• Beighton P, de Paepe A, Danks D, et al. International nosology of heritable disorders of connective tissue, Berlin,
1986. Am J Med Genet. 1988;29:581-594. Abstract

• Svensson LG, Blackstone EH, Feng J, et al. Are Marfan syndrome and marfanoid patients distinguishable on long-term
follow-up? Ann Thorac Surg. 2007;83:1067-1074. Abstract

• Nemet AY, Assia EI, Apple DJ, et al. Current concepts of ocular manifestations in Marfan syndrome. Surv Ophthalmol.
2006;51:561-575. Abstract

• Svensson LG, Crawford ES. Marfan syndrome and connective tissue disorders. In: Svensson LG, Crawford ES, eds.
Cardiovascular and vascular disease of the aorta. Philadelphia, PA: WB Saunders; 1997:84-104.

• Svensson LG, Khitin L. Aortic cross-sectional area/height ratio timing of aortic surgery in asymptomatic patients
with Marfan syndrome. J Thorac Cardiovasc Surg. 2002;123:360-361. Abstract

• Svensson LG, Deglurkar I, Ung J, et al. Aortic valve repair and root preservation by remodeling, reimplantation, and
tailoring: technical aspects and early outcome. J Card Surg. 2007;22:473-479. Abstract

• Habib G, Lancellotti P, Antunes MJ, et al. 2015 ESC Guidelines for the management of infective endocarditis. Eur
Heart J. 2015;36:3075-3128. Full text Abstract

• Habashi JP, Judge DP, Holm TM, et al. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of
Marfan syndrome. Science. 2006;312:117-121. Abstract

References
1. Pyeritz AE. The Marfan syndrome. Annu Rev Med. 2000;51:481-510. Abstract

2. Beighton P, de Paepe A, Danks D, et al. International nosology of heritable disorders of connective tissue, Berlin,
1986. Am J Med Genet. 1988;29:581-594. Abstract

3. Grimes SJ, Acheson LS, Mathews AL, et al. Clinical consult: Marfan's syndrome. Prim Care. 2004;31:739-742, xii.
Abstract

4. Arslan-Kirchner M, Arbustini E, Boileau C, et al. Clinical utility gene card for: Marfan syndrome type 1 and related
phenotypes [FBN1]. Eur J Hum Genet. 2010;18:ejhg.2010.42. Full text Abstract

5. Francke U, Furthmayr H. Marfan's syndrome and other disorders of fibrillin. N Engl J Med. 1994;330:1384-1385.
Abstract

6. Svensson LG, Crawford ES, Coselli JS, et al. Impact of cardiovascular operation on survival in the Marfan patient.
Circulation. 1989;80:I233-I242. Abstract

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 Marfan's syndrome References

7. Svensson LG, Blackstone EH, Feng J, et al. Are Marfan syndrome and marfanoid patients distinguishable on long-term
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This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Jan 07, 2016.
36 BMJ Best Practice topics are regularly updated and the most recent version of the topics can be found on bestpractice.bmj.com . Use
of this content is subject to our disclaimer. © BMJ Publishing Group Ltd 2016. All rights reserved.
Marfan's syndrome Images

Images

Figure 1: Positive thumb sign

From the collection of LG Svensson, E Mendrinos, C Pournaras

IMAGES
Figure 2: Impact of aortic dissection on patient survival
From the collection of LG Svensson, E Mendrinos, C Pournaras

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 Marfan's syndrome Disclaimer

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38 BMJ Best Practice topics are regularly updated and the most recent version of the topics can be found on bestpractice.bmj.com . Use
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Contributors:

// Authors:

Anne Child, MD, FRCP

Honorary Consultant
Cardiology and Genetics, Department of Cardiac and Vascular Sciences, St George's, University of London, London, UK
DISCLOSURES: AC is an author of a number of references cited in this monograph.

Maite Tome, PhD

Consultant Cardiologist
Honorary Senior Lecturer , St George’s Hospital, University Hospitals NHS Foundation Trust , London , UK
DISCLOSURES: MT declares that she has no competing interests.

// Peer Reviewers:

Daniel Judge, MD
Assistant Professor of Medicine
Medical Director, JHU Center for Inherited Heart Disease, Johns Hopkins Hospital, Baltimore, MD
DISCLOSURES: DJ declares that he has no competing interests.

Reed E. Pyeritz, MD, PhD

Professor of Medicine and Genetics
University of Pennsylvania, Philadelphia, PA
DISCLOSURES: REP declares that he has no competing interests.