Marfan syndrome
Connective tissue is the body's packing material: the fibers and sheets that give skin, blood vessels, ligaments and other structures their strength and stretch. Marfan syndrome weakens one of those fibers, so tissues that should be firm and elastic become too loose. People with Marfan are often tall and long-limbed with flexible joints, but the most important effects are inside, on the eyes, the skeleton and especially the large blood vessel leaving the heart.
Marfan syndrome is autosomal dominant, caused by mutations in the FBN1 gene that encodes fibrillin-1, a protein that forms elastic microfibrils. A single faulty copy is enough to cause the disorder, and an affected parent has a 50 percent chance of passing it to each child. Beyond simply weakening fibers, the faulty fibrillin also disturbs signaling by a growth factor (TGF-beta), which contributes to the features.
The disorder varies widely even within a family, an example of variable expressivity. The most serious risk is to the aorta, which can enlarge and tear; for this reason people with Marfan are monitored, and this entry is educational reference, not medical advice. Some historical tall figures have been speculated to have had Marfan, though such retrospective diagnoses are uncertain.
A tall teenager with long fingers, lens dislocation in one eye, and a family history is evaluated; imaging shows early aortic enlargement and a FBN1 mutation confirms Marfan syndrome.
One faulty gene touches eyes, bones and the aorta at once, the essence of pleiotropy.
Marfan illustrates pleiotropy, where one gene affects many seemingly unrelated traits (eye, skeleton, heart), and variable expressivity, where the same mutation produces different degrees of severity.