Question 78

Question:

A man with a history of hyperextensible joints and aortic insufficiency presents for a genetic screening. He is discovered to have a homozygous defect in the gene that encodes the glycoprotein fibrillin. What are the chances that his son will have the same disease?

Correct Answer: E.  100%

This patient has Marfan syndrome with a characteristic defect in the fibrillin gene. Since he is homozygous and since fibrillin is inherited in an autosomal dominant fashion, his son will certainly be affected as well.

Marfan’s gene is FBN-1 (fibrillin) on chromosome 15. Fibrillin connects to the extracellular matrix and also TGF-beta. Excess TGF-beta is also proposed as part of the pathophysiological mechanism for Marfan’s physiological symptoms.

Marfan’s diagnosis: long limbs, dislocated lenses, and aortic root dilation