Diagnosis

What is diagnosis?

- The diagnosis of Marfan syndrome can be complicated because the combination of clinical symptoms and their severity are very diverse.
- No laboratory tests are available for routine diagnosis.
- Identification of the mutation in the FBN1 gene for fibrillin can be used in diagnostics, but DNA tests are used only in specific cases.
- Learn more about the FBN1 gene, mutations and DNA tests here >>>.
- DNA testing alone is not sufficient to make a diagnosis of Marfan syndrome.

An accurate diagnosis of Marfan syndrome can only be made after a complete medical examination, focusing primarily on the heart, eyes and skeleton (in this order!). The information on this page is not intended for self-examination!

Cardiological examination of the heart
Cardiological examination is primary one. Aortic enlargement is an essential criterion for diagnosis and is the most life-threatening for patient. Echocardiogram (ultrasound image of the heart) focused mainly on measurement of aortic width in the area of ​​Valsalva sinus, valve prolapse, and regurgitation.

Eye examination by ophthalmologist

Biomicroscopically and in mydriasis (when the pupils are enlarged). The displacement of the lens, especially in a certain direction, is very rare in other diseases and therefore this sign is important for the diagnosis of Marfan syndrome. Ectopia lentis also occurs in homocystinuria and Weill-Marchesani syndrome.

Examination of the skeleton by orthopaedist

Examination of skeletal signs, especially chest and spine deformities. Typically, a thumb and wrist symptom or an altered upper / lower body segment ratio and a height / arm ratio are characteristic.

Genetic examination by a clinical geneticist

The history of clinical signs of the disease in the family is examined. DNA tests are only relevant in specific cases.
 

Marfan syndrome is diagnosed when the patient has a combination of clinical symptoms according to the Ghent criteria.

Recently used criteria from 1996 relied on the evaluation of characters as "main" and "minor". In 2010, new criteria were published in the Journal of Medical Genetics (Loeys et al. 2010).

According to the revised Ghent criteria from r. 2010, there are two key symptoms in MFS diagnostics: 

  • aortic root dilatation (Z-score ≥ 2) or aortic dissection - "Ao"
  • ectopia lentis - "EL"

1 / In the absence of family history of MFS (i.e. new mutation):

- the simultaneous occurrence of these two key symptoms is sufficient to clearly diagnose Marfan syndrome, irrespective of the existence of other characteristics, unless otherwise indicated, alternative diagnosis:

  • Ao (Z ≥ 2) + EL = MFS

- in the absence of one of these two key symptoms, the presence of a known FBN1 mutation or a combination of system signs is required. They have a new scoring system. In this way, DNA testing is not mandatory, but is useful if available:

  • Ao (Z ≥ 2) + FBN1 = MFS

  • Ao (Z ≥ 2) + System signs (≥ 7 points) = MFS (signs resembling SGS, LDS, or vEDS should be excluded)

  • EL + FBN1 mutation associated with aortic disease = MFS

2 / If MFS is already confirmed in the family (as above):

- the presence of only one of the criteria is sufficient to make a diagnosis of Marfan syndrome:

  • family history of MFS + EL = MFS

  • family history of MFS + System signs (≥ 7 points) = MFS (characters resembling SGS, LDS, or vEDS should be excluded)

  • family history of MFS + Ao (Z ≥ 2 over 20 years, ≥ 3 to 20 years) = MFS (characters resembling SGS, LDS, or vEDS should be excluded)

(SGS = Sprintzen-Goldberg sy, LDS = Loeys-Dietz sy, vEDS = vascular form of Ehlers-Danlos sy)

   The scheme for determining the diagnosis of MFS (from MJA 197(9), 2012, p. 494-497.).

ATTENTION: A person may have one or more marfanoid symptoms, but Marfan syndrome may not be confirmed, eg:

  • In children (sometimes in adults), other symptoms of Marfan syndrome may occur later.
  • The absence of aortic dilatation in the initial clinical examination does not necessarily exclude the diagnosis of MFS, even in adults. Regular annual cardiovascular and ophthalmological examination are therefore recommended. 
  • In some cases, the person has another congenital connective tissue disease or metabolic disorder that causes similar clinical symptoms to those seen in Marfan syndrome (related diseases), even in the case of a FBN1 mutation. 
  • Irrespective of diagnosis, regular examinations and therapy are required for each symptom present.

A Diagnostic Tool for Healthcare Professionals

Marfan foundation in US has prepared a diagnostic tool www.marfan.org/dx/.

Please note: Information on this site is not a substitution for the professional healthcare. They are for informational purposes only and may not be used for treatment, prevention or diagnosis without the previous consultation with the physician.