Marfan syndrome

Definition

Marfan syndrome is an inheritable disorder of connective tissue (which adds strength to the body's structures) that affects the skeletal system, cardiovascular system, eyes, and skin.

Causes, incidence, and risk factors

Marfan syndrome is inherited as an autosomal dominant trait. However, up to 30% of cases have no family history and are so called "sporadic" cases. In sporadic cases, Marfan syndrome is believed to result from a spontaneous new mutation.

Marfan syndrome is caused by mutations in the gene fibrillin-1. Fibrillin-1 plays an important role as the "scaffolding" for elastic tissue in the body. Disruption of such scaffolding (by mutations in fibrillin-1) thus results in changes in elastic tissues, particularly in the aorta, eye, and skin. Mutations in fibrillin-1 also cause overgrowth of the long bones of the body, resulting in the tall stature and long limbs seen in Marfan patients.

How this overgrowth happens is not well understood. Marfan syndrome causes skeletal defects typically recognized in a tall, lanky person with long limbs and spider-like fingers (arachnodactyly), chest abnormalities (pectus excavatum or pectus carinatum), curvature of the spine, and a particular set of facial features, including a highly arched palate and crowded teeth.

Common eye problems are nearsightedness and dislocation of the lens of the eye.

The most significant of the defects in the syndrome are cardiovascular abnormalities, which may include enlargement (dilatation) of the base of the aorta (aortic root), with aortic regurgitation, and prolapse of the mitral valve. Affected people may develop a dissecting aortic aneurysm.

Symptoms

• Family history of Marfan syndrome
  
• Long, lanky frame
  
• Long, thin limbs
  
• Armspan significantly greater than body height
  
• Long, spidery fingers (arachnodactyly)
  
• Funnel chest (pectus excavatum) or pigeon breast (pectus carinatum)
  
• Scoliosis
  
• Visual difficulties
  
• Flat feet
  
• Learning disability/school problems
  
• Thin, narrow face
  
• Micrognathia (small lower jaw)
  
• Coloboma of iris
  
• Hypotonia
  

Signs and tests
A physical examination may show:

• Joint laxity (hypermobile joints)