What are the clinical features of Marfan syndrome?

Clinical Features of Marfan Syndrome

Marfan syndrome is characterized by multisystem involvement affecting the cardiovascular, ocular, skeletal, pulmonary, and integumentary systems, with cardiovascular complications being the primary cause of morbidity and mortality. 1

Diagnostic Features

Cardiovascular System

• Aortic root dilation: The most critical feature requiring regular monitoring
  • Typically begins at the sinuses of Valsalva
  • Predisposes to aortic dissection, the most life-threatening complication 1
• Mitral valve prolapse and regurgitation
• Aortic regurgitation (secondary to aortic root dilation)
• Dilatation may extend to other parts of the aorta 1

Ocular System

• Ectopia lentis (lens dislocation): A highly specific feature that helps differentiate Marfan syndrome from related disorders 1
• Myopia
• Increased risk of retinal detachment 2

Skeletal System

• Tall stature with disproportionately long limbs (dolichostenomelia)
• Arachnodactyly (long, slender fingers)
• Joint hypermobility
• Pectus deformities:
  • Pectus carinatum (protruding sternum): More specific for Marfan syndrome
  • Pectus excavatum (sunken sternum)
• Scoliosis or kyphosis
• Dolichocephaly (elongated head)
• Characteristic hand signs:
  • Wrist sign (thumb and fifth finger overlap when encircling wrist)
  • Thumb sign (thumb extends beyond ulnar border when fisted) 1

Other Systems

• Dural ectasia (ballooning of the dural sac)
• Striae atrophica (stretch marks) without significant weight changes
• Recurrent or incisional hernias
• Pneumothorax
• Reduced muscle mass and adipose tissue
• Emerging features in long-term survivors: renal and hepatic cysts 1

Diagnostic Criteria (Revised Ghent Nosology)

Without Family History of Marfan Syndrome

Diagnosis can be made with any of these combinations:

1. Dilated aortic root (Z-score > +2) AND ectopia lentis
2. Dilated aortic root AND pathogenic FBN1 mutation
3. Dilated aortic root AND systemic score ≥7 points
4. Ectopia lentis AND FBN1 mutation associated with aortic disease 1

With Family History of Marfan Syndrome

Diagnosis can be made with any of these:

1. Ectopia lentis
2. Systemic score ≥7 points
3. Dilated aortic root (Z-score > +2 if over 20 years; Z-score > +3 if under 20 years) 1

Systemic Features Scoring

• Wrist AND thumb sign = 3 points (wrist OR thumb sign = 1 point)
• Pectus carinatum = 2 points (pectus excavatum/chest asymmetry = 1 point)
• Hindfoot deformity = 2 points (flat feet = 1 point)
• Pneumothorax = 2 points
• Dural ectasia = 2 points
• Protrusio acetabuli = 2 points
• Other features contribute additional points 1

Management Considerations

Cardiovascular Monitoring

• Regular echocardiographic monitoring is essential:
  • Normal aortic root: Every 2-3 years
  • Aortic root <4.5 cm with slow growth: Annual echocardiogram
  • Aortic root >4.5 cm or rapid growth (>0.5 cm/year): Echocardiogram every 6 months 1, 2
• Complete imaging of the entire aorta with MRI or CT in young adulthood 2
• Beta-blocker therapy is standard treatment 1, 2
• Angiotensin receptor blockers may be considered as alternative or adjunctive therapy 2
• Surgical intervention when aortic root diameter reaches 4.5 cm or shows rapid growth 1

Multidisciplinary Approach

• Annual evaluation for scoliosis until skeletal maturity 2
• Regular ophthalmologic assessment for refractive errors and ectopia lentis 3
• Genetic testing to confirm diagnosis and for family screening 2
• Avoidance of high-intensity static exercise 3

Important Clinical Pitfalls

1. Delayed diagnosis: The penetrance of some features is age-dependent, making diagnosis in children challenging 3
2. Overlooking related disorders: Conditions like Loeys-Dietz syndrome can present similarly but have different management implications 1, 4
3. Pregnancy risks: Women with aortic roots >4 cm have increased risk during pregnancy 3
4. Incomplete evaluation: Failure to image the entire aorta may miss aneurysms beyond the root 1
5. Inadequate follow-up: Even after surgical repair, continued medical therapy and monitoring are essential 2

Marfan syndrome remains primarily a clinical diagnosis despite advances in genetic testing, with FBN1 mutations detected in 90-95% of classic cases 1. A multidisciplinary approach involving cardiologists, ophthalmologists, orthopedists, and geneticists is crucial for comprehensive management 5.