Loeys-Dietz syndrome.

Loeys-Dietz syndrome is an autosomal dominant aortic aneurysm syndrome characterized by multisystemic involvement. The most typical clinical triad includes hypertelorism, bifid uvula or cleft palate and aortic aneurysm with tortuosity. Natural history is significant for aortic dissection at smaller aortic diameter and arterial aneurysms throughout the arterial tree. The genetic cause is heterogeneous and includes mutations in genes encoding for components of the transforming growth factor beta (TGFβ) signalling pathway: TGFBR1, TGFBR2, SMAD3 and TGFB2. Despite the loss of function nature of these mutations, the patient-derived aortic tissues show evidence of increased (rather than decreased) TGFβ signalling. These insights offer new options for therapeutic interventions.