What diagnostic testing is recommended for individuals presenting with possible mild symptoms of Marfan syndrome?

Diagnostic Testing for Suspected Marfan Syndrome

For individuals with possible mild symptoms of Marfan syndrome, comprehensive diagnostic testing should include echocardiography, ophthalmologic examination, genetic testing for FBN1 mutations, and skeletal assessment based on the revised Ghent nosology criteria. 1

Initial Diagnostic Evaluation

Clinical Assessment

• Detailed physical examination to evaluate:
  • Height, arm span, and upper/lower segment ratio
  • Skeletal features (wrist and thumb signs, pectus deformities, hindfoot deformities)
  • Facial features (hypertelorism, bifid uvula/cleft palate)
  • Skin for striae
  • Joint hypermobility using the Beighton scale 2, 1

Cardiovascular Assessment

• Echocardiogram to:
  • Measure aortic root dimensions (Z-score calculation)
  • Evaluate for mitral valve prolapse (present in 66% of Marfan patients) 3
  • Assess for aortic regurgitation
  • Measure main pulmonary artery diameter (cutoff value of 23 mm for adults) 3

Ophthalmologic Evaluation

• Slit-lamp examination to detect:
  • Ectopia lentis (lens dislocation)
  • Myopia and other ocular manifestations 1

Advanced Imaging

• MRI or CT angiography of the entire aorta (particularly important in young adults) 2, 1
• MRI to assess for dural ectasia 1, 4
• X-rays for evaluation of:
  • Protrusio acetabuli
  • Scoliosis measurement 1

Genetic Testing

• FBN1 gene sequencing (mutations found in 66% of clinically diagnosed Marfan syndrome patients) 5
• Consider additional testing for related disorders if FBN1 testing is negative:
  • TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3 gene sequencing (for Loeys-Dietz syndrome) 1

Diagnostic Criteria Application

Apply the revised Ghent nosology criteria, which requires a combination of:

• Aortic root dilation (Z-score ≥2 in adults, ≥3 in children)
• Ectopia lentis
• Systemic features scoring (≥7 points needed)
• FBN1 mutation 1

Important Considerations

Diagnostic Challenges

• Age-related manifestations may delay diagnosis, particularly in children 5
• Some patients initially diagnosed with isolated ectopia lentis may develop other Marfan features later in life 4
• Long-term follow-up is essential as some manifestations like dural ectasia may develop late (age range 32-64 years) 4

Differential Diagnosis

• Evaluate for related disorders:
  • Loeys-Dietz syndrome
  • Familial thoracic aortic aneurysm and dissection
  • Ehlers-Danlos syndrome (hypermobile type) 2

Follow-up Recommendations

• For normal aortic root size: Echocardiogram every 2-3 years until adult height is reached 2
• For aortic root dilation:
  • Annual echocardiogram if diameter <4.5 cm and growth rate <0.5 cm/year
  • Echocardiogram every 6 months if diameter >4.5 cm or growth rate >0.5 cm/year 2, 1
• Regular ophthalmologic examinations
• Periodic MRI/CT of the entire aorta, especially with history of aortic root replacement or dissection 1

The diagnostic yield is significantly higher in patients with aortic root dilation (70% using the 2010 Ghent nosology) 6, emphasizing the importance of thorough cardiovascular assessment even in mild cases.