The Finding That Aberrant Tgf-b Signalling Was Involved

in the pathogenesis of LDS prompted Loeys et al. [4] to investigate the role of TGF-b in MFS. It emerged that increased TGF-b levels and activity was evident in preclinical models and patients with MFS, a phenomenon explained by the fact that TGF-b is normally sequestered (and regulated) in the extracellular matrix by binding to fibrillin [7]. Moreover, suppression of TGF-b in preclinical models and individuals with MFS led to disease arrest [8 10]. This was achieved either by administration of TGF-b1-neutralizing antibodies or by delivery of angiotensin II antagonists, which, through reasons that are incompletely understood, are able to suppress TGF-b levels. Indeed, Losartan prevented aortic aneurysm development in an MFS mouse model [8] and delayed aortic root enlargement in 18 children with MFS [9]. Perindopril was shown to reduce aortic root measurements and improve arterial compliance in adult patients with MFS [10]. Several large randomized controlled trials are ongoing across the USA and Europe. Management of LDS involves regular MRA surveillance scans to establish the extent of vascular involvement, early surgical intervention, genetic counselling and monitoring in pregnancy. TGF-b antagonism with angiotensin II receptor blockers is recommended, as this may confer a similar protective effect to that observed in MFS. Our case emphasizes the importance of considering LDS in the adult rheumatology population and highlights the emerging role of TGF-b inhibition in halting disease in a range of inherited connective tissue disorders linked by a common pathogenic pathway.