Marfan syndrome
Marfan syndrome is a genetic disorder that affects the body's connective tissue, often causing abnormalities in the heart, blood vessels, eyes, bones, and joints.
Overview
Connective tissue provides strength and flexibility to structures such as bones, ligaments, muscles, blood vessels, and heart valves. Because this tissue is found throughout the body, Marfan syndrome can affect many systems with varying severity and progression. The incidence of the condition is approximately 1 in 5,000 worldwide.
Symptoms
The two primary features of Marfan syndrome are vision problems caused by a dislocated lens (ectopia lentis) and defects in the aorta, the large blood vessel that distributes blood from the heart. The aorta can weaken and stretch, leading to an aneurysm or a sudden tearing of the vessel wall (aortic dissection), which can be life-threatening.
Other common features include:
- Heart issues: Mitral valve prolapse or aortic valve regurgitation, which can cause shortness of breath, fatigue, and palpitations.
- Skeletal features: Tall and slender stature, elongated fingers and toes (arachnodactyly), loose joints, an arm span exceeding body height, a long and narrow face, crowded teeth, and abnormal curvature of the spine (scoliosis).
- Chest abnormalities: Sunken chest (pectus excavatum) or protruding chest (pectus carinatum).
- Respiratory and neurological: Spontaneous pneumothorax (collapsed lung) and dural ectasia (enlargement of the membrane surrounding the brain and spinal cord), which can cause back, leg, or head pain.
- Eye issues: Nearsightedness, clouding of the lens, and increased pressure within the eye (glaucoma).
Causes
Marfan syndrome is caused by mutations in the FBN1 gene, which provides instructions for making the protein fibrillin-1. This protein forms threadlike filaments called microfibrils that provide strength and flexibility to connective tissue. Microfibrils also bind to growth factors; when FBN1 mutations reduce functional fibrillin-1, excess growth factors are released, leading to tissue overgrowth and instability.
Inheritance
This condition is inherited in an autosomal dominant pattern. At least 25 percent of cases result from a new mutation in the FBN1 gene in people with no family history of the disorder.