ABNORMAL MORPHOLOGY OF FIBRILLIN MICROFIBRILS IN FIBROBLAST-CULTURES FROM PATIENTS WITH NEONATAL MARFAN-SYNDROME

The Marfan syndrome (MFS) is a connective tissue disorder manifested b y variable pleiotropic features In the skeletal, ocular, and cardiovas cular systems. The average life span in MFS is about 35 years. A group with much more severe cardiovascular disease and a mean life span of approximately I year also exists. We refer to this latter group as ''n eonatal Marfan syndrome'' (nMFS). Fibrillin defects are now known to b e the cause of MFS and nMFS. Immunofluorescence studies were the first to demonstrate this association. Here we describe immunofluorescence studies in a series of to neonates and summarize their salient clinica l features. In vitro accumulation of fibrillin reactive fibers was ass ayed using monoclonal antibodies to fibrillin in hyperconfluent fibrob last cultures. As was previously observed in MTS, fibroblast cultures from nMFS patients showed an apparent decrease in accumulation of immu nostainable fibrillin. Significantly, however, the morphology of the i mmunostained fibrils in the nMFS cultures were abnormal and differed n ot only from control cultures, but also from those seen in cultures of MFS fibroblasts. The nMFS fibrils appeared short, fragmented and fray ed, characteristics that are not seen in MFS. Both the clinical and fi brillin morphology data provide evidence to suggest a useful subclassi fication of nMFS in the spectrum of MFS.