Marfan syndrome: What internists and pediatric or adult cardiologists need to know

Marfan syndrome (MFS) is one of the most frequent connective tissue disorders, showing striking pleiotropism and clinical variability. There is autosomal dominant inheritance with complete penetrance but variable expression. Approximately 25% of MFS patients have no family history of the syndrome and represent sporadic cases due to new mutations. This hazardous condition is often associated with premature cardiovascular death unless surveillance and management are optimized. The fibrillin gene (FBN1) encodes the structure of the connective tissue protein fibrillin. MFS is caused by mutations in the fibrillin gene, located on chromosome 15 at locus 15q21. Fibrillin abnormalities reduce the structural integrity of different body systems, primarily involving the heart valves, blood vessels, lungs, bones, tendons, ligaments, cartilages, eyes, skin, spinal dura and the CNS. Patients with MFS are likely to have too little fibrillin within these structures, resulting in clinically relevant problems. For example, in the aortic wall, deficient fibrillin may trigger progressive aortic ectasia and may result in aortic dissection.