Marfan syndrome

Background

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

Autosomal-dominant mutation in FBN1 gene (encodes collagen matrix protein 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)

In the absence of family history:

In the presence of family history:

 * Z Score > 2 (if age > 20 years)
 * Z Score > 3 (if age < 20 years)
 and Family History of MFS

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
- 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)

Authors: