Traboulsi syndrome caused by mutations in ASPH: An autosomal recessive disorder with overlapping features of Marfan syndrome

Traboulsi syndrome, otherwise known as facial dysmorphism, lens dislocation, anterior-segment abnormalities and spontaneous filtering blebs, is an autosomal recessive condition associated with characteristic ocular features including dislocated crystalline lenses, anterior segment abnormalities and in some individuals, non-traumatic conjunctival cysts. There is a distinctive facial appearance which includes flattened malar region with convex nasal ridge. Alterations in the aspartate beta-hydroxylase (ASPH) gene are known to be the cause of the condition. We report seven further individuals from six unrelated families with characteristic ocular and facial features. Five individuals had aortic root dilatation, with childhood onset in some, and one undergoing aortic root repair aged 47 years for severe aortic regurgitation and aortic mot dilatation. Interestingly, inguinal hernias were commonly reported. Although some skeletal features were seen, these were not consistent. One of the patients had mild deficiency of factor VII on clotting studies. The ASPH protein hydroxylates specific asparagine- and aspartate-residues in epidermal growth factor (EGF)-domain containing proteins including coagulation factors and associated genes including FBNI . We propose this as an explanation for the overlap in clinical features with Marfan syndrome and conclude that Traboulsi syndrome is an important differential diagnosis. We strongly recommend echocardiography surveillance for patients with Traboulsi syndrome.

Automated summary

Traboulsi syndrome, a rare genetic disorder characterized by ocular and facial abnormalities, is associated with mutations in the ASPH gene. In addition to the characteristic eye and face features, patients may also experience aortic root dilation and inguinal hernias. This syndrome shares clinical features with Marfan syndrome and echocardiography surveillance is recommended for Traboulsi syndrome patients.