Marfan Syndrome                                                                                  Click to print page

Professor Antoine Marfan (1858 - 1942) from France described this condition in Bull Mem Soc Med Hop Paris 1896;13:220-226. It affects about 1 person in every 10,000.

It is an autosomal dominant condition and so there are often several people in the family affected.  However Marfan syndrome develops in 25% of people due to a spontaneous mutation. The responsible gene is located at chromosome 15q21.1 4 but over 100 different mutations have been described. It causes an abnormality of fibrillin which is an important component of elastic microfibrill and 350 kD glycoprotein.Marfan Syndrome on Online Mendelian Inheritance in Man (OMIM) or Genetest.org.

Follow this link for more general details about Marfan Syndrome on Online Mendelian Inheritance in Man (OMIM) or Genetests

 Marfan Habitus

Marfan syndrome is a variable condition with some people only very mildly affected. In childhood it rarely causes difficulties. Sometimes it can be difficult to be sure whether or not the condition is present as not everyone has all the signs and there is no reliable test - if this is the case then it may be necessary to review the children as they grow older to see if they truly have the condition or not.

The diagnosis should be based on the Ghent diagnostic criteria (De Paepe et al. Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet 1996;62:417–26)

  • The initial assessment should include a personal history, detailed family history, and clinical examination including ophthalmology examination and transthoracic echocardiogram
  • The development of scoliosis and protrusio acetabulae is age dependent, commonly occurring following periods of rapid growth. Radiographic examination for these features is indicated, depending on age, if a positive finding would make the diagnosis of Marfan syndrome
  • A pelvic MRI scan to detect dural ectasia is indicated if a positive finding would make the diagnosis of Marfan syndrome
  • Younger patients with suspected Marfan syndrome, who do not fulfill the Ghent diagnostic criteria, should be offered repeat clinical evaluations pre-school, before puberty, and at age 18, if they fall into one of the groups below. Additional evaluations may be clinically indicated around puberty:
    1. Children or adolescents with a positive family history in whom DNA testing is not possible
    2. Children or adolescents with no family history, who fall short of fulfilling the diagnostic criteria by one system only.

Diagnostic Requirements – “Ghent criteria”
Index case - If family or genetic history is not contributory major criteria in at least two different organ systems plus involvement of a third organ system. If the mutation known to cause Marfan syndrome in others is detected One major criterion in an organ system plus involvement of a second organ system.

Relative of index case - Presence of a major criterion in the family history and a major criterion in an organ system plus involvement of a second organ system

System

Ghent Diagnostic Criteria

Major

Minor

Skeletal system

pectus carinatum

pectus excavatum of moderate severity

 

pectus excavatum requiring surgery

joint hypermobility

 

reduced upper-to-lower segment ratio or arm span-to-height ratio greater than 1.05

highly arched palate with crowding of teeth

 

 

facial appearance (dolichocephaly, malar hypoplasia, down-slanting palpebral fissures, retrognathia)

 

wrist and thumb signs

 

 

scoliosis of > 20° or spondylolisthesis

 

 

reduced extension at the elbows (< 170°)

enophthalmos

 

medial displacement of the medial malleolus causing pes planus

 

 

protrusio acetabulae of any degree (ascertained on radiographs)

 

For skeletal system to be considered involved, at least 2 of the components comprising the major criterion or 1 component comprising the major criterion plus 2 of the minor criteria must be present.

Ocular system

ectopia lentis

abnormally flat cornea

 

 

increased axial length of globe

 

 

hypoplastic iris or hypoplastic ciliary muscle

For ocular system to be involved, at least 2 of the minor criteria must be present.

Cardiovascular system

dilatation of the ascending aorta with or without aortic regurgitation and involving at least the sinuses of Valsalva

mitral valve prolapse with or without mitral valve regurgitation

 

 

dilatation of the main pulmonary artery

 

dissection of the ascending aorta

calcification of mitral annulus

 

 

dilatation or dissection of the descending thoracic or abdominal aorta

For the cardiovascular system to be involved, a major criterion or only one of the minor criteria must be present.

Pulmonary system

none

spontaneous pneumothorax, or apical blebs (ascertained by chest radiography)

For the pulmonary system to be involved, one of the minor criteria must be present.

Skin and integument

none

striae atrophicae (stretch marks) not associated with marked weight changes, pregnancy, or repetitive stress, or

 

 

recurrent or incisional herniae

For the skin and integument to be involved, one of the minor criteria must be present.

Dura

lumbosacral dural ectasia by CT or MR image

none

For the dura to be involved, the major criterion must be present.

Family/Genetic History

having parent, child, or sibling who meets these diagnostic criteria independently

none

 

presence of mutation in FBN1, known to cause Marfan syndrome; or

 

 

presence of haplotype around FBN1inherited by descendent known to be associated with unequivocally diagnosed Marfan syndrome in the family

 

For the family/genetic history to be contributory, one of the major criteria must be present.
Wrist Sign Thumb Sign

Wrist Sign

Thumb Sign
Pes Planus Elbow Extension

Pes Planus

Elbow Extension

Cardiac Problems

In childhood some 80% have silent mitral valve prolapse (ie. without clinical signs and thus no significant mitral regurgitation). 50% can be demonstrated to have a dilated aortic root.

Dilated aortic root

 MRI - aortic aneurysm

Natural History

Without treatment the aortic root dilation progresses and death is through aneurymal rupture or aortic dissection. The mean survival reported by Gray et al was  43 years.

Management

It has now been shown (Shores et al) that treatment with B blockers limits the progression of aortic dilation.

The risk of sudden death increases with the aortic root diameter and emergency operations carry a significantly higher mortality than elective root replacement. Current practice is to undertake surgery when the root size is greater than 5.5 cm (in some centre 5.0 cm) or the rate of progression is more than 2 mm per year (5% per year in children).

Various surgical techniques are possible. The Bentall operation first undertaken in 1968 replaces both the aortic valve, aortic root and ascending aorta. More recently techniques have evolved in an attempt to preserve the native aortic valve whenever possible.

Prognosis

In those who require surgery the current surgical mortality rates are low - less than 2% and the overall survival in Marfan Syndrome has increased to 72 years (Silverman DI et al). 

An excellent review on the management of Marfan syndrome can be found in Heart 2002;88:97-103 by JC Dean. More information on Marfan Syndrome can be found on the US National Library of Medicine Medline Plus Health Information website.

Diagnosis Gent Criteria Cardiac Problems Natural History Management Prognosis

This page was last edited 19/2/2004
 

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