Marfan syndrome

Background

• Marfan syndrome (MFS) is a heritable connective tissue disorder with multi-system involvement
  • First described by Antoine Marfan in 1896
  • Clinical features vary along a spectrum typical of autosomal-dominant disorders

• Autosomal-dominant mutation in FBN1 gene (encoding fibrillin-1) on chromosome 15
  • This results in cystic medial degeneration of the aortic tunica media (leading to increased risk of aortic aneurysm / dissection)
  • This also interferes with elastin deposition during extracellular matrix formation implicates in the elasticity of multiple tissue types
  • Majority of cases (75%) are familial / inherited vs. minority (25%) are de novo mutations

• Estimated prevalence of 1/5000 individuals worldwide (equal between men and women)

• Life expectancy for those diagnosed and treated is now close to that of non-MFS population (previously expected increase in patient mortality by third and fourth decades of life)

Clinical Features

• Tall stature, long extremities and digits, scoliosis, pectus excavatum
• Ligamentous laxity, hyperextensibility
• Myopia due to lens dislocation
• Dural ectasia (low back pain, paresthesias/numbness, bowel/bladder dysfunction)
• Mitral valve prolapse (~85%), mitral regurgitation
• High arched palate

Increased risk of:

• Aortic dissection that begin at the root of the aorta
  • Even higher risk in pregnancy
• Aortic regurgitation
• Severe mitral regurgitation: elongated chordae tendinae can occasionally rupture
• Subarachnoid hemorrhage
• Spontaneous pneumothorax
• Cervical spine injury (due to ligamentous laxity)
• Lens dislocation, retinal detachment