The Marfan Foundation

Know the signs. Fight for victory.

Summary of Diagnostic Criteria

The diagnosis of Marfan syndrome relies on a set of defined clinical criteria (the Ghent nosology) developed to facilitate accurate recognition of the syndrome and improve patient management and counseling.

To decrease the risk of premature or missed diagnosis, an international panel of experts revised the criteria in 2010. It was published in the Journal of Medical Genetics.

The new diagnostic criteria puts more weight on the cardiovascular manifestations of the disorder. Aortic root aneurysm and ectopia lentis (dislocated lenses) are now cardinal features.

  • In the absence of any family history, the presence of these two features is sufficient for the unequivocal diagnosis of Marfan syndrome.
  • In the absence of one of these two cardinal features, the presence of an FBN1 mutation of positive systemic score is required.
  • In some cases, genetic testing can be helpful. 

Experts expect that, while use of new diagnostic criteria makes a definitive diagnosis of Marfan syndrome take longer, it decreases the risk of premature or missed diagnosis and facilitates a worldwide discussion of risk and follow-up/management guidelines.

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

In the absence of family history:

  1. Aortic Root Dilatation Z score ≥ 2 AND Ectopia Lentis = Marfan syndrome - 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 Marfan syndrome, regardless of the presence or absence of systemic features except where these are indicative of Shprintzen Goldberg syndrome, Loeys-Dietz syndrome, or vascular Ehlers Danlos syndrome.
  2. Aortic Root Dilatation Z score ≥ 2 AND FBN1 = Marfan syndrome - 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. Aortic Root Dilatation Z score ≥ 2 AND Systemic Score ≥ 7pts = Marfan syndrome - 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 Marfan syndrome diagnosis is confirmed by the presence of sufficient systemic findings (≥ 7 points, according to a scoring system) confirms the diagnosis. However, features suggestive of Shprintzen Goldberg syndrome, Loeys-Dietz syndrome, or vascular Ehlers Danlos syndrome 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. Ectopia lentis AND FBN1 with known Aortic Root Dilatation = Marfan syndrome - 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 Marfan syndrome.

In the presence of family history:

  1. Ectopia lentis AND Family History of Marfan syndrome (as defined above) = Marfan syndrome - The presence of ectopia lentis and a family history of Marfan syndrome (as defined in 1-4 above) is sufficient for a diagnosis of Marfan syndrome.
  2. A systemic score ≥ 7 points AND Family History of Marfan syndrome (as defined above) = Marfan syndrome - A systemic score of greater than or equal to 7 points and a family history of Marfan syndrome (as defined in 1-4 above) is sufficient for a diagnosis of Marfan syndrome. However, features suggestive of Shprintzen Goldberg syndrome, Loeys-Dietz syndrome, or vascular Ehlers Danlos syndrome 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.
  3. Aortic Root Dilatation Z score ≥ 2 above 20 yrs. old, ≥ 3 below 20 yrs. old) + Family History of Marfan syndrome (as defined above) = Marfan syndrome - The presence of aortic root dilatation (Z ≥ 2 above 20 yrs. old, ≥ 3 below 20 yrs. old) and a family history of Marfan syndrome (as defined in 1-4 above) is sufficient for a diagnosis of Marfan syndrome. However, features suggestive of Shprintzen Goldberg syndrome, Loeys-Dietz syndrome, or vascular Ehlers Danlos syndrome 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.

Caveat: Without discriminating features of Shprintzen Goldberg syndrome, Loeys-Dietz syndrome, or vascular Ehlers Danlos syndrome - AND after TGFBR1/2, collagen biochemistry, COL3A1 testing if indicated – other conditions/genes will emerge with time.

For a listing of laboratories that perform molecular testing, visit GeneTests