Pathogenesis
Marfan syndrome is caused by mutations in the FBN1 gene on chromosome 15, which encodes fibrillin 1, a glycoprotein component of the extracellular matrix. Fibrillin-1 is essential for the proper formation of the extracellular matrix, including the biogenesis and maintenance of elastic fibers. The extracellular matrix is critical for both the structural integrity of connective tissue, but also serves as a reservoir for growth factors. Elastic fibers are found throughout the body, but are particularly abundant in the aorta, ligaments and the ciliary zonules of the eye; consequently, these areas are among the worst affected. It can also be caused by a range of intravenous crystal treatments in those susceptible to the disorder.A transgenic mouse has been created carrying a single copy of a mutant fibrillin-1, a mutation similar to that found in the human gene known to cause MFS. This mouse strain recapitulates many of the features of the human disease and promises to provide insights into the pathogenesis of the disease. Reducing the level of normal fibrillin 1 causes a Marfan-related disease in mice.Transforming growth factor beta (TGF-β) plays an important role in MFS. Fibrillin-1 directly binds a latent form of TGF-β, keeping it sequestered and unable to exert its biological activity. The simplest model suggests reduced levels of fibrillin-1 allow TGF-β levels to rise due to inadequate sequestration.
On the contrary, Toiler suggested that the breakdown of proliferating cells of the follicle after impeded eruption is likely to be the origin of the dentigerous cyst. The breakdown products may result in increased osmotic tension, resulting in cyst formation. The exact histogenesis of dentigerous cysts remains unknown, but most authors favor a developmental origin from the tooth follicle. In 1928, Bloch-Jorgensen suggested that the overlying necrotic deciduous tooth is the origin of all dentigerous cysts. The resultant periapical inflammation might spread to involve the follicle of the unerupted permanent successor, an inflammatory exudate ensued with resultant dentigerous cyst formation. He reported 22 cases of follicular cysts and stated that in each case a deciduous tooth or the remnants thereof was found in direct contact with the cyst cavity and that the related deciduous tooth always was diseased. Azaz and Shteyer similarly suggested that the persistent and prolonged periapical inflammation caused chronic irritation to the follicle of the successors. This may trigger and hasten the formation of a dentigerous cyst developing around the permanent teeth. They reported five cases of dentigerous cysts which involved the second mandibular premolar in four children aged 8 to 11 years old. These children were referred for extraction of carious, nonvital primary molars with swelling of the surrounding soft tissue. Occlusal radiographs showed buccal expansion of bone at the affected site. The primary teeth were not in direct contact with the underlying dentigerous cyst. It has been suggested that dentigerous cysts may be either extrafollicular or intrafollicular in origin.