Ectopia lentis + FBN1 variant known to cause aortic disease
Marfan syndrome
Family history + ectopia lentis OR Systemic ≥ 7 OR Aortic Z-score ≥ 2
Marfan syndrome (familial criteria)
Section 3
Pearls/Pitfalls
Key Pearls
Aortic root Z-score ≥ 2 is the cardinal criterion — order TTE in all suspected Marfan patients; track aortic root annually.
Ectopia lentis (lens dislocation) requires slit-lamp examination by ophthalmologist — present in ~60% of Marfan patients.
FBN1 testing detects a variant in ~93% of cases meeting Ghent-2 criteria — but 7% are genotype-negative phenotypic Marfan.
Children < 20yr: Systemic score ≥ 7 alone is NOT sufficient for diagnosis without aortic root enlargement, ectopia lentis, or FBN1 variant — natural growth can affect systemic features.
Differential Diagnoses (Overlap Conditions)
MASS phenotype: Mitral prolapse, aortic root < 2 SD, skin, skeletal features; FBN1 variant but no aortic enlargement.
Aortic root ≥ 4.5cm or rapidly growing: Prophylactic aortic root surgery (Bentall or valve-sparing); class I recommendation (ESC 2014).
03
All patients: Beta-blocker therapy (atenolol) or losartan to reduce aortic dilatation rate; contact sport restriction.
04
FBN1 confirmed: Cascade testing of 1st degree relatives; reproductive counselling (50% AD transmission).
Section 5
Evidence Appraisal
Primary Reference
The revised Ghent nosology for the Marfan syndrome
Loeys BL et al. • Journal of Medical Genetics. 2010;47(7): 476–485
Section 6
Literature
Ghent-1 (1996) and Revision
The original Ghent nosology (1996) was the first internationally standardised diagnostic framework for Marfan syndrome, requiring major and minor criteria across multiple organ systems. The Ghent-2 revision (Loeys et al., 2010) simplified the framework, gave greater weight to two pathognomonic features (ectopia lentis and aortic root dilatation), and removed features with low specificity (high-arched palate, joint hypermobility).
Impact of FBN1 Discovery
FBN1 was identified as the Marfan syndrome gene in 1991 by Francesco Ramirez's group. The Ghent-2 criteria incorporated FBN1 genotyping, enabling molecular confirmation as a standalone diagnostic pathway. Over 3,000 FBN1 variants are now reported in the context of Marfan or Marfan-related conditions in UMD-FBN1 and ClinVar.
