Over the past decade, the medical community has slowly accepted the idea that patients presenting with aortic aneurysms and dissections are part of a wide spectrum of genetically mediated diseases that present in syndromic as well a non-syndromic forms. Marfan syndrome (MFS) has long been the only seriously considered differential diagnosis in terms of a heritable disorder of connective tissue in patients with aortic aneurysm. MFS is an autosomal dominant disorder affecting about 1 in 5000 individuals. The phenotypic changes of MFS are imposed by mutations in the gene encoding for the extracellular matrix protein fibrillin-1 (Dietz et al., 1991). It has been shown that aneurysm formation in MFS is driven by excessive transforming growth factor-β (TGF-β) signaling through the “non-canonical” pathway via extracellular signal-regulated kinase (pERK)(Habashi et al., 2011; Holm et al., 2011). TGF-β is a ubiquitous cytokine in most mammalian cells and involved in cellular proliferation and differentiation. Ten years ago Loeys and Dietz identified a subset of patients sharing certain features such as a bifid uvula, hypertelorism and marked tortuosity of the vessels that had not been typically associated with MFS. The group identified mutations in the gene encoding for the TGF-β receptors 1 and 2 as the causative mutation (Loeys et al., 2006; Loeys et al., 2005). Identifying Loeys-Dietz syndrome (LDS) as a separate entity was important as patients with LDS suffered from acute aortic dissection at aortic diameters that had not been considered a cut-off to proceed to surgery in MFS patients. Therefore, the diagnosis LDS carries immediate therapeutic consequences and has made genetic testing an important step in evaluating patients with aortic aneurysms for surgery.

The initial patients were mostly children with a strong phenotype that had been referred to Loeys and Dietz since they clearly exhibited a syndromatic phenotype but did not fit other known aneurysm syndromes. Meanwhile the phenotype has broadened and it has been realized that eg a bifid uvula is not an essential feature in diagnosing LDS (Loeys et al., 2005).