Mutations in the gene for fibrillin-1 (FBN1) have been shown to cause Marfan 
syndrome, an autosomal dominant disorder of connective tissue characterised by 
pleiotropic manifestations involving primarily the ocular, skeletal, and 
cardiovascular systems. Fibrillin-1 is a major component of the 10-12 nm 
microfibrils, which are thought to play a role in tropoelastin deposition and 
elastic fibre formation in addition to possessing an anchoring function in some 
tissues. Fibrillin-1 mutations have also been found in patients who do not 
fulfil clinical criteria for the diagnosis of Marfan syndrome, but have related 
disorders of connective tissue, such as isolated ectopia lentis, familial aortic 
aneurysm, and Marfan-like skeletal abnormalities, so that Marfan syndrome may be 
regarded as one of a range of type 1 fibrillinopathies. There appear to be no 
particular hot spots since mutations are found throughout the entire fibrillin-1 
gene. However, a clustering of mutations associated with the most severe form of 
Marfan syndrome, neonatal Marfan syndrome, has been noted in a region 
encompassing exons 24 to 32. The gene for fibrillin-2 (FBN2) is highly 
homologous to FBN1, and mutations in FBN2 have been shown to cause a 
phenotypically related disorder termed congenital contractural arachnodactyly. 
Since mutations in the fibrillin genes are likely to affect the global function 
of the microfibrils, the term microfibrillopathy may be the most appropriate to 
designate the spectrum of disease associated with dysfunction of these 
molecules. The understanding of the global and the molecular functions of the 
fibrillin containing microfibrils is still incomplete and, correspondingly, no 
comprehensive theory of the pathogenesis of Marfan syndrome has emerged to date. 
Many, but not all, fibrillin-1 gene mutations are expected to exert a dominant 
negative effect, whereby mutant fibrillin monomers impair the global function of 
the microfibrils. In this paper we review the molecular physiology and 
pathophysiology of Marfan syndrome and related microfibrillopathies.