Marfan's syndrome

Abstract

Marfan's syndrome is a systemic disorder of connective tissue caused by mutations in the extracellular matrix protein fibrillin 1. Cardinal manifestations include proximal aortic aneurysm, dislocation of the ocular lens, and long-bone overgrowth. Important advances have been made in the diagnosis and medical and surgical care of affected individuals, yet substantial morbidity and premature mortality remain associated with this disorder. Progress has been made with genetically defined mouse models to elucidate the pathogenetic sequence that is initiated by fibrillin-1 deficiency. The new understanding is that many aspects of the disease are caused by altered regulation of transforming growth factor beta (TGFbeta), a family of cytokines that affect cellular performance, highlighting the potential therapeutic application of TGFbeta antagonists. Insights derived from studying this mendelian disorder are anticipated to have relevance for more common and non-syndromic presentations of selected aspects of the Marfan phenotype.

Figure:

Aortic root growth curves normalised to body size and age The left graph is for children and adolescents, the middle graph is for adults younger than 40 years, and the right graph is for adults older than 40 years. The shaded areas represent the range of values in which 95% of the population will fall. Modified from The American Journal of Cardiology with permission of Elsevier.