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The diagnosis of Marfan syndrome (MFS) relies on a set of international criteria, outlined by expert opinion. In 1996, the initial Berlin nosology was revised because of the risk of over diagnosis and redefined as the Ghent nosology, a more stringent set of major and minor criteria. These Ghent criteria have proven to work well since with improving molecular techniques, confirmation of the diagnosis is possible in over 95% of patients. However, concerns with the Ghent criteria are that some of the diagnostic manifestations have not been validated as “hinge points” (eg. dural ectasia) and others necessitate cumbersome imaging studies. Moreover, in the absence of aortic dilation, the diagnosis can be stigmatizing, hamper career aspirations and restrict life-insurance opportunities. The label “MFS” may cause psychosocial burden by “restricted exercise permission” and situational depression. 

Following a recent international expert meeting, the Ghent nosology was revised and has now been been published in the Journal of Medical Genetics.

In the 2010 revised Ghent nosology, aortic root aneurysm and ectopia lentis are now cardinal features.  In absence of any family history, the presence of these two manifestations is sufficient for the unequivocal diagnosis of MFS. In absence of any of these two, the presence of bonafide FBN1 mutation or a combination of systemic features is required. For the latter a new scoring system has been designed and validated. In this way FBN1 testing is not mandatory but useful when available. The 2010 revised Ghent nosology puts more weight on the cardiovascular manifestations of the disease. It is anticipated that the 2010 nosology will delay a definitive diagnosis of MFS but decreases the risk of premature or misdiagnosis and facilitates discussion of risk and follow-up/management guidelines.

The 2010 Revised Ghent Nosology for Marfan syndrome relies on 7 rules as indicated below:

 (See below for key of abbreviations)

In the absence of family history:

1.  Ao (Z ≥ 2) AND EL = MFS

2.  Ao (Z ≥ 2) AND FBN1 = MFS

3.  Ao (Z ≥ 2) AND Syst (≥ 7pts) = MFS*     

4.  EL AND FBN1 with known Ao = MFS

In the presence of family history:

5.  EL AND FH of MFS (as defined above) = MFS

6.  Syst (≥ 7 pts) AND FH of MFS (as defined above) = MFS*

7.  Ao (Z ≥ 2 above 20 yrs old, ≥ 3 below 20 yrs) + FH of MFS (as defined above) = MFS*  

*  Caveat: Without discriminating features of SGS, LDS or vEDS

            - AND after TGFBR1/2, collagen biochemistry, COL3A1 testing if indicated

            - other conditions/genes will emerge with time 

Click here to calculate the systemic score

Click here for information about differential diagnosis

Click here for criteria for causal FBN1 mutation

Click here for Z-Score Calculation

Click here for information on discriminating features of related disorders

For a listing of laboratories that perform molecular testing visit

1.  The presence of aortic root dilatation (Z-score ≥ 2 when standardized to age and body size) or dissection and ectopia lentis allows the unequivocal diagnosis of MFS, irrespective of the presence or absence of systemic features except where these are indicative of SGS, LDS or vEDS.
   
   
2. The presence of aortic root dilatation (Z ≥ 2) or dissection and the identification of a bona fide FBN1 mutation are sufficient to establish the diagnosis even when ectopia lentis is absent.
   
   
3. Where aortic root dilatation (Z ≥ 2) or dissection is present but ectopia lentis is absent and the FBN1 status is either unknown or negative, a MFS diagnosis is confirmed by the presence of sufficient systemic findings (≥ 7 points, according to a scoring system) confirms the diagnosis. However, features suggestive of SGS, LDS or vEDS must be excluded and appropriate alternative genetic testing (TGFBR1/2, collagen biochemistry, COL3A1, and other relevant genetic testing when indicated and available upon the discovery of other genes) should be performed.
   
   
4. In the presence of ectopia lentis but absence of aortic root dilatation/dissection, the identification of an FBN1 mutation previously associated with aortic disease is required before making the diagnosis of MFS.
   
   
5. The presence of ectopia lentis and a family history of MFS (as defined in 1 - 4 above) is sufficient for a diagnosis of MFS.
   
   
6. A systemic score of greater than or equal to 7 points and a family history of MFS (as defined in 1 - 4 above) is sufficient for a diagnosis of MFS. However, features suggestive of SGS, LDS or vEDS must be excluded and appropriate alternative genetic testing (TGFBR1/2, collagen biochemistry, COL3A1, and other relevant genetic testing when indicated and available upon the discovery of other genes) should be performed.
   
   
7. The presence of aortic root dilatation (Z ≥ 2 above 20 yrs old, ≥ 3 below 20 yrs) and a family history of MFS (as defined in 1 - 4 above) is sufficient for a diagnosis of MFS.  However, features suggestive of SGS, LDS or vEDS must be excluded and appropriate alternative genetic testing (TGFBR1/2, collagen biochemistry, COL3A1, and other relevant genetic testing when indicated and available upon the discovery of other genes) should be performed.
   

Key of Abbreviations

Ao= aortic diameter at the sinuses of valsalva above indicated Z-score or aortic root dissection,
Z = Z-score
EL=ectopia lentis
Syst = systemic score
FBN1= fibrillin-1 mutation
FBN1 with known Ao = FBN1 mutation that has been identified in an individual with aortic aneurysm
FBN1 not known with Ao = FBN1 mutation that has not previously been associated aortic root aneurysm/dissection
MFS = Marfan syndrome  

SGS = Sprintzen Goldberg syndrome

LDS = Loeys-Dietz syndrome

vEDS = Vascular Ehlers Danlos syndrome

TGFBR1/2 = Transforming Growth Factor Beta Receptor 1/2

COL3A1 = Collagen 3A1