fibrillin

Fibrillin refers to a family of large extracellular glycoproteins that assemble into microfibrils, which provide scaffolding for elastic fibers in connective tissues. In humans, the most studied members are fibrillin-1 (encoded by FBN1) and fibrillin-2 (FBN2).

Fibrillin monomers polymerize to form extracellular microfibrils that interweave with elastin to create elastic fibers, supporting tissues such as skin, lungs, blood vessel walls, and ligaments. Microfibrils also regulate signaling by binding latent TGF-β complexes and affecting growth factor availability.

Molecular structure of fibrillin includes numerous calcium-binding EGF-like domains and TB (tetrabrachion-like) domains, arranged in long, modular repeats. This architecture enables polymerization into beaded microfibrils and selective interactions with elastin and other matrix components.

Genetic mutations in FBN1 cause Marfan syndrome, a dominantly inherited connective tissue disorder characterized by cardiovascular, skeletal, and ocular manifestations, including aortic root dilatation and lens dislocation. Mutations in FBN2 cause congenital contractural arachnodactyly (Beals syndrome).

Pathophysiology reflects defective microfibril assembly and dysregulated TGF-β signaling, leading to weakened vessel walls and abnormal tissue development. The resulting aortic dilatation is a major clinical concern in Marfan syndrome.

Management focuses on monitoring and reducing cardiovascular risk, using beta-blockers or losartan to limit TGF-β signaling, along with surgical repair as needed. Eye and skeletal manifestations are addressed with appropriate specialty care.