Rheumatology Practice Test

Mutations in FBN1 disrupt fibrillin-1, a key component of elastic microfibrils in connective tissue. This weakens the connective tissue framework and underlies Marfan syndrome, an autosomal dominant disorder. Clinically, Marfan features include tall stature with long limbs and arachnodactyly, lens displacement, and aortic root dilation with risk of dissection due to weakened arterial walls. The other conditions listed involve different genes or chromosomal abnormalities (Klinefelter is an autosomal sex-chromosome disorder; Alport affects collagen IV in the kidney, ear, and eye; Chediak-Higashi is a lysosomal trafficking disorder). Thus, FBN1 mutations are associated with Marfan syndrome.