Guidelines for the diagnosis and management of Marfan syndrome.

1.1 Definition and prevalence Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder involving the cardiovascular, skeletal and ocular systems, the integument, lungs and dura. Cardinal manifestations include aortic aneurysm and dissection, ocular lens dislocation and long bone overgrowth. In 90-93% of cases, MFS is caused by mutations in FBN1. Mutations in a second gene, TGFBR2, have been shown to cause MFS, designated MFS2. Current early estimates quote this gene as responsible for up to 10% of all MFS cases. The prevalence of MFS is at least 1/5,000 and 25% of cases are sporadic. Penetrance is extremely high. Isolated cases with no family history are often more severely affected. Several examples of “homozygous” MFS have been reported. Gonadal mosaicism is rare (probably <1%). Compound heterozygosity at the FBN1 locus is very rare.