Diagnostic Criteria for Marfan Syndrome (MFS)

Marfan syndrome is currently diagnosed using criteria based on an evaluation of the family history, molecular data, and 6 organ systems.

Diagnostic Criteria for Marfan Syndrome (MFS)


The Ghent criteria consist of major and minor criteria. The major criteria are features or symptoms that are common in people with Marfan syndrome and rare in people who do not have the syndrome.

Minor criteria are features or symptoms that are present in people with Marfan syndrome, but are also present in people who do not have it.

To be diagnosed with Marfan syndrome using the Ghent criteria, you must have a number of different criteria as described below.

If you have a family history of Marfan syndrome, you will need to have one of the major criteria and one of the minor criteria that affect different systems in your body, such as your skeleton and your blood vessels.
If you do not have a family history of Marfan syndrome, you will need to have two major criteria and one of the minor criteria that affect different systems in your body.

Index case:

• Major criteria in 2 different organ systems
• AND involvement of a third organ system.

Relative of index case:

• 1 major criterion in family history
• AND 1 major criterion in an organ system
• AND involvement in second organ system.

SKELETAL

Major (Presence of at least 4 of the following manifestations)

• pectus carinatum
• pectus excavatum requiring surgery
• reduced upper to lower segment ratio OR arm span to height ratio >1.05
• wrist (Note 2) and thumb (Note 3) signs
• scoliosis of >20° or spondylolisthesis
• reduced extension at the elbows (<170°)
• medial displacement of the medial malleolus causing pes planus
• protrusio acetabulae of any degree (ascertained on radiographs)

Minor

• pectus excavatum of moderate severity
• joint hypermobility
• high arched palate with crowding of teeth
• facial appearance
• dolichocephaly,
• malar hypoplasia,
• enophthalmos,
• retrognathia,
• down-slanting palpebral fissures
• INVOLVEMENT: 2 major criteria or 1 major and 2 minor

OCULAR

Major

• ectopia lentis

Minor

• flat cornea
• increased axial length of the globe
• hypoplastic iris OR hypoplastic ciliary muscle causing decreased miosis
• INVOLVEMENT: 2 minor criteria

CARDIOVASCULAR

Major

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

Minor

• mitral valve prolapse with or without mitral valve regurgitation
• dilatation of the main pulmonary artery, in the absence of valvular or peripheral pulmonic stenosis below the age of 40 years
• calcification of the mitral annulus below the age of 40 years
• dilatation or dissection of the descending thoracic or abdominal aorta below age of 50 years
• INVOLVEMENT: 1 minor criterion

PULMONARY

Minor (only)

• spontaneous pneumothorax
• apical blebs
• INVOLVEMENT: 1 minor criterion

SKIN AND INTEGUMENT

Minor (only)

• striae atrophicae
• recurrent or incisional hernia
• INVOLVEMENT: 1 minor criterion

DURA

Major

• lumbosacral dural ectasia by CT or MRI

FAMILY/GENETIC HISTORY

Major

• first degree relative who independently meets the diagnostic criterion.
• presence of mutation in FBN1 known to cause Marfan syndrome
• presence of haplotype around FBN1 inherited by descent and unequivocally associated with diagnosed Marfan syndrome in the family

References:

1. Radonic T, de Witte P, Groenink M, de Bruin-Bon RA, Timmermans J, Scholte AJ, van den Berg MP, Baars MJ, van Tintelen JP, Kempers M, Zwinderman AH, Mulder BJ. Critical appraisal of the revised Ghent criteria for diagnosis of Marfan syndrome. Clin Genet. 2011 Oct;80(4):346-53. [Medline]
2. Loeys BL, Dietz HC, Braverman AC, Callewaert BL, De Backer J, Devereux RB, Hilhorst-Hofstee Y, Jondeau G, Faivre L, Milewicz DM, Pyeritz RE, Sponseller PD, Wordsworth P, De Paepe AM. The revised Ghent nosology for the Marfan syndrome. J Med Genet. 2010 Jul;47(7):476-85. [Medline]
3. De Paepe A, Devereux RB, Dietz HC, Hennekam RC, Pyeritz RE. Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet. 1996 Apr 24;62(4):417-26. [Medline]