Marfan syndrome

Marfan syndrome was initially mapped to chromosome 15q
by linkage studies and subsequently shown to be associated with
mutations in the fibrillin 1 gene (FBN1). Fibrillin is the major
constituent of extracellular microfibrils and is widely
distributed in both elastic and non-elastic connective tissue
throughout the body. FBN1 mutations have been found in
patients who do not fulfil the full diagnostic criteria for
Marfan syndrome, including cases with isolated ectopia lentis,
familial aortic aneurysm and patients with only skeletal
manifestations. FBN1 is a large gene containing 65 exons. Most
Marfan syndrome families carry unique mutations and more
than 140 different mutations have been reported. Screening
new cases for mutations is not routinely available, and
diagnosis depends on clinical assessment. Mutations in the
fibrillin 2 gene (FBN2) cause the phenotypically related
disorder of contractural arachnodactyly (Beal syndrome)
characterised by dolichostenomelia (long slim limbs) with
arachnodactyly, joint contractures and a characteristically
crumpled ear.