What is the recommended evaluation and management for a patient suspected of having Marfan syndrome?

Marfan Syndrome: Evaluation and Management

Patients suspected of having Marfan syndrome require immediate referral to a medical geneticist or cardiologist for comprehensive evaluation using the revised Ghent criteria, with echocardiography and ophthalmologic examination as the cornerstone diagnostic tests to prevent life-threatening aortic dissection. 1, 2

Diagnostic Evaluation

Essential Clinical Assessment

Physical examination must systematically evaluate skeletal features using a scoring system where ≥7 points indicates systemic involvement: 1

• Wrist AND thumb sign = 3 points (wrist OR thumb sign = 1 point) 1
• Pectus carinatum = 2 points (pectus excavatum or chest asymmetry = 1 point) 1
• Hindfoot deformity = 2 points (plain pes planus = 1 point) 1
• Pneumothorax = 2 points 1
• Dural ectasia = 2 points 1
• Protrusio acetabuli = 2 points 1

Required Diagnostic Testing

Order these tests immediately for any suspected case: 2

• Echocardiogram to measure aortic root diameter with Z-score calculation (>2 standard deviations above mean for age, sex, and body surface area is diagnostic) 1, 2
• Dilated ophthalmologic examination to assess for ectopia lentis 2, 3
• Detailed three-generation family history focusing on aortic disease, sudden death, or Marfan features 2

Diagnostic Criteria Without Family History

The diagnosis is established if ANY of the following are present: 1

• Aortic root Z-score ≥2 PLUS ectopia lentis 1
• Aortic root Z-score ≥2 PLUS pathogenic FBN1 mutation 1
• Aortic root Z-score ≥2 PLUS systemic score ≥7 points 1
• Ectopia lentis PLUS FBN1 mutation previously associated with aortic disease 1

Diagnostic Criteria With Positive Family History

If a first-degree relative has independently confirmed Marfan syndrome, the diagnosis is established with ANY of: 1

• Ectopia lentis alone 1
• Systemic score ≥7 points alone 1
• Aortic root Z-score ≥2 (if age >20 years) or Z-score ≥3 (if age <20 years) 1

Role of Genetic Testing

FBN1 genetic testing is NOT required for diagnosis when clinical criteria are met, but can be helpful in equivocal cases. 1, 4 Testing detects mutations in only 90-95% of clinically definite cases, so a negative result does not exclude Marfan syndrome. 1 Marfan syndrome remains fundamentally a clinical diagnosis. 1

Cardiovascular Management

Confirmed Marfan Syndrome or Aortic Root Dilation

Initiate beta-blocker therapy immediately to slow aortic growth and reduce hemodynamic stress. 1, 2, 5

Surveillance imaging frequency depends on aortic root diameter and growth rate: 1, 2, 5

• Annual echocardiogram if aortic root <4.5 cm in adults AND growth rate <0.5 cm/year 1, 2
• Every 6 months if aortic root >4.5 cm in adults OR growth rate >0.5 cm/year 1, 2, 5
• MRI or CT of entire aorta starting in young adulthood, repeated every 2-3 years (annually if history of aortic root replacement or dissection) 1, 5

Surgical Intervention Thresholds

Refer for prophylactic aortic repair when: 1, 5

• Aortic root diameter >4.5 cm 1
• Growth rate >1 cm/year 1
• Progressive aortic regurgitation 1
• Diameter 4.0 cm in women contemplating pregnancy 5

Management of Suspected Cases Without Confirmed Diagnosis

For patients with some marfanoid features but not meeting full diagnostic criteria: 1

• Repeat echocardiogram every 2-3 years until adult height reached 1
• If aortic root remains normal after reaching adult height, repeat only if cardiovascular symptoms develop or major increase in physical activity is planned 1
• The aortic root should not exceed 40-42 mm even in tall individuals 1

Critical Differential Diagnoses

Loeys-Dietz Syndrome

Distinguish by presence of: 2

• Bifid uvula or cleft palate 2
• Craniosynostosis 2
• Arterial tortuosity 2
• Characteristic facial features (hypertelorism, broad nasal bridge) 2

This condition has HIGHER risk of dissection at smaller aortic diameters than Marfan syndrome. 1

Hypermobile Ehlers-Danlos Syndrome

Distinguish by: 1, 2

• Beighton score ≥5/9 for joint hypermobility 1, 2
• Soft, velvety skin (rarely seen in Marfan) 1
• Easy bruising and chronic pain 1, 2
• Functional GI disorders 1, 2

Aortic root dilation occurs in only 25-33% of cases and dissection risk is minimal without significant dilation. 1

Familial Thoracic Aortic Aneurysm

Some families have isolated aortic disease without other Marfan features. 1 These patients require the same cardiovascular surveillance as Marfan syndrome but lack skeletal and ocular manifestations. 1

Key Clinical Pitfalls

Do not falsely reassure patients with some marfanoid features and normal initial aortic measurements - continue surveillance every 2-3 years until adult height is reached, as aortic dilation can develop later. 1

Do not rely solely on genetic testing - approximately 5-10% of clinically definite Marfan cases have negative FBN1 testing. 1

Do not miss ectopia lentis - this requires dilated ophthalmologic examination by an experienced ophthalmologist, as it may be subtle. 2, 3

Do not assume all tall, thin individuals with joint hypermobility have Marfan syndrome - systematically apply the diagnostic criteria and consider alternative diagnoses like Ehlers-Danlos syndrome or Loeys-Dietz syndrome. 1, 2