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 (not all may be present)
- Tall stature, long extremities
- Reduce upper-to-lower segment ratio, increased arm span-to-height ratio
- Arachnodactyly (“wrist sign, thumb sign), reduced elbow extension
- Scoliosis or thoracolumbar kyphosis
- Pectus excavatum or carinatum
- Ligamentous laxity, hyperextensibility
- Protrusio acetabuli
- Hindfoot deformity, plain flat foot
- Ectopia lentis
- Myopia (often severe); retinal detachment
- Lumbrosacral dural ectasia
- Dolichocephaly, downward slanting palpebral fissures, enophthalmos, retrognathia, malar hypoplasia, high arched palate
- Skin striae
Increased risk of:
- Acute Aortic Syndrome (AAS)
- Thoracic aortic aneurysm
- [thoracic aortic dissection|Stanford Types A and B Aortic Dissection]
- Intramural Hemotoma (IMH)
- Mitral valve prolapse (present in up to 60%) and mitral regurgitation
- Spontaneous pneumothorax (associated with bullae, 4-11%)
- Subarachnoid hemorrhage (SAH)
- Controversial link between Marfan Syndrome and intracranial aneurysms (more clearly associated with vEDS and LDS)
- Ocular Lens dislocation, retinal detachment
- Spinal conditions (scoliosis; lumbosacral disease; dural ectasia)
- Musculoskeletal injuries due to joint laxity (laxity in 85% of children, 56% of adults)
- Complications during pregnancy (risk of aortic dissection)
- Type A dissection risk increases with aortic dilation; Type B risk poorly understood. (aortic dissection in up to 4.5%, primarily peripartum)