Marfan syndrome is a genetic disease that affects connective tissue. It can show different degrees of clinical severity and pleiotropy. The disorder is due to heterozygous mutations FBN1, which encodes the protein fibrillin-1, a key element of the connective tissue matrix. However, there is also a smaller number of patients that would present mutations in TGFBR2 and TGFBR3 (receptors, transforming growth factor beta-2 and beta-3), showing at times a more aggressive phenotype.
The main features of Marfan syndrome result in an alteration of the cardiovascular (dilation of the aorta at the level of the sinuses of Valsalva, predisposition to tearing of the aortic wall ...), skeletal (bone overgrowth disproportion, joint laxity , scoliosis ...) and eye (myopia, increased chance of developing retinal detachment ...).
Marfan syndrome is inherited in an autosomal dominant, in which about 75% of patients have an affected parent, and in which the rest of the sick individuals present mutations novo.
The pathogenesis of Marfan syndrome is complex. It has been observed that the fibrillin-1 mutant is able to behave with dominant negative activity, interfering with normal protein of wild allele, significantly reducing the number of microfibrils available. Furthermore, Marfan syndrome can also be caused by mutations that involve gene deletion or premature termination, reducing protein expression.