How do I diagnose Marfan syndrome using the revised Ghent criteria?

Diagnosing Marfan Syndrome Using the Revised Ghent Criteria

The revised Ghent nosology (2010) prioritizes aortic root aneurysm/dissection and ectopia lentis as the two cardinal features, with diagnosis requiring either both of these features together, or one cardinal feature plus an FBN1 mutation, or one cardinal feature plus a systemic score ≥7 points. 1

Core Diagnostic Algorithm

In Patients WITHOUT a Family History of Marfan Syndrome:

Diagnosis requires one of the following combinations: 1

1. Aortic root dilation (Z-score ≥2) AND ectopia lentis - this alone is sufficient for definitive diagnosis 1

2. Aortic root dilation (Z-score ≥2) AND a pathogenic FBN1 mutation 1

3. Aortic root dilation (Z-score ≥2) AND systemic score ≥7 points 1

4. Ectopia lentis AND a pathogenic FBN1 mutation known to cause aortic disease 1

In Patients WITH a Family History of Marfan Syndrome:

Diagnosis requires one of the following: 1

1. Ectopia lentis alone 1

2. Systemic score ≥7 points alone 1

3. Aortic root dilation (Z-score ≥2 above 20 years old, Z-score ≥3 below 20 years old) 2, 1

Essential Diagnostic Workup

Cardiovascular Assessment:

• Transthoracic echocardiography (TTE) is mandatory at initial diagnosis to measure aortic root diameter at multiple levels: annulus, sinuses of Valsalva, sinotubular junction, and ascending aorta 2

• Calculate Z-scores accounting for age, sex, and body surface area - aortic root should not exceed 40-42 mm even in tall individuals 3

• CT or MRI of the entire thoracic aorta is reasonable after initial TTE to confirm measurements and assess segments not visualized by echocardiography 2

• Evaluate for mitral valve prolapse, aortic regurgitation, and tricuspid regurgitation 2

Ophthalmologic Assessment:

• Dilated slit-lamp examination by an ophthalmologist is mandatory to detect ectopia lentis 4, 3

• Ectopia lentis is pathognomonic for Marfan syndrome and essentially rules out Ehlers-Danlos syndrome 4

Systemic Score Calculation (Maximum 20 Points):

The systemic score assigns points for specific skeletal and extra-skeletal features: 1

• Wrist AND thumb sign: 3 points (wrist OR thumb sign: 1 point)
• Pectus carinatum deformity: 2 points (pectus excavatum or chest asymmetry: 1 point)
• Hindfoot deformity: 2 points
• Pneumothorax: 2 points
• Dural ectasia: 2 points
• Protrusio acetabuli: 2 points
• Reduced upper segment/lower segment ratio AND increased arm span/height ratio AND no severe scoliosis: 1 point
• Scoliosis or thoracolumbar kyphosis: 1 point
• Reduced elbow extension (≤170°): 1 point
• Facial features (3/5): dolichocephaly, enophthalmos, downslanting palpebral fissures, malar hypoplasia, retrognathia: 1 point
• Skin striae: 1 point
• Myopia >3 diopters: 1 point
• Mitral valve prolapse: 1 point

A score ≥7 indicates systemic involvement 1

Genetic Testing:

• FBN1 genetic testing is not mandatory but carries greater diagnostic weight in the revised criteria 1

• When performed, FBN1 mutations are detected in approximately 86-95% of patients meeting clinical criteria 5, 1

• Genetic testing enables definitive diagnosis in 95% of tested patients and helps differentiate related disorders 5

Additional Imaging When Indicated:

• Lumbosacral MRI or CT for dural ectasia assessment if it would change diagnostic classification (contributes 2 points to systemic score) 3

Critical Diagnostic Pitfalls

Common Misdiagnosis Scenarios:

Distinguishing from Ehlers-Danlos Syndrome (EDS):

• EDS features soft, velvety, hyperextensible skin (major criterion) - Marfan skin is rarely hyperextensible 4
• EDS requires Beighton score ≥5/9 with more severe generalized joint laxity - Marfan has milder hypermobility 4
• EDS does NOT cause ectopia lentis 4
• EDS has only mild aortic root dilation (no dissection risk without significant dilation) versus Marfan's significant root dilation with high dissection risk 4

Age-Related Considerations:

• In children under 20 years, aortic root Z-score ≥3 is required (versus Z-score ≥2 in adults) 2

• Some patients initially classified as ectopia lentis syndrome or MASS phenotype may develop full Marfan syndrome over time, requiring ongoing surveillance 6

Systemic Score Limitations:

• Only 39-40% of patients fulfill criteria for systemic involvement (≥7 points), limiting its standalone diagnostic utility 5

• The systemic score is most helpful when neither aortic dilation nor ectopia lentis is present, or when genetic testing is unavailable 1

Reclassification Under Revised Criteria

Compared to the 1996 Ghent criteria, the revised nosology leads to different diagnoses in approximately 15% of cases: 6

• 10% of patients previously diagnosed with Marfan syndrome are reclassified as ectopia lentis syndrome or MASS phenotype in the absence of aortic dilation 6

• 5% are newly classified as Marfan syndrome when aortic dilation is present 6

• 83-89% of FBN1 mutation-positive patients meet revised criteria for Marfan syndrome 6

Alternative Diagnoses to Consider

When revised Ghent criteria are not met, consider: 1

• Ectopia lentis syndrome (ectopia lentis with FBN1 mutation but no aortic dilation)
• MASS phenotype (Mitral valve prolapse, Aorta borderline, Skin/Skeletal findings, but no ectopia lentis)
• Loeys-Dietz syndrome (requires genetic testing for TGFBR1/TGFBR2 mutations)
• Potential Marfan syndrome in patients <20 years who may develop full criteria with time