Aneurysm Syndromes Caused by Mutations in the TGF-β Receptor

Background The Loeys–Dietz syndrome is a recently described autosomal dominant aortic-aneurysm syndrome with widespread systemic involvement. The disease is characterized by the triad of arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate and is caused by heterozygous mutations in the genes encoding transforming growth factor β receptors 1 and 2 (TGFBR1 and TGFBR2, respectively). Methods We undertook the clinical and molecular characterization of 52 affected families. Forty probands presented with typical manifestations of the Loeys–Dietz syndrome. In view of the phenotypic overlap between this syndrome and vascular Ehlers–Danlos syndrome, we screened an additional cohort of 40 patients who had vascular Ehlers–Danlos syndrome without the characteristic type III collagen abnormalities or the craniofacial features of the Loeys–Dietz syndrome. Results We found a mutation in TGFBR1 or TGFBR2 in all probands with typical Loeys–Dietz syndrome (type I) and in 12 probands presenting ...