Variable ocular phenotypes of posterior polymorphous corneal dystrophy caused by mutations in the ZEB1 gene

To describe the ocular features of 6 Czech and British patients with posterior polymorphous corneal dystrophy (PPCD) caused by mutations in the zinc finger E-box binding homeobox 1 gene (ZEB1).

Case note review of 4 individuals with p.E776fs mutation, one with p.Y719X and one with p.F375fs mutation within the ZEB1 gene.

Five individuals exhibited endothelial and Descemet membrane changes consistent with the diagnosis of PPCD. We concluded that one 70-year-old female who had a normal endothelium at both slit lamp and non-contact specular microscopy was a case of non-penetrance. The onset of disease was as early as 3 months after birth. One patient had irregular astigmatism with inferior corneal steepening on videokeratography, but without corneal thinning or other signs of keratoconus. Two others had corneal steepening >49D but with regular astigmatism. Three individuals underwent penetrating keratoplasty (PK) in 1 eye, with one patient treated for secondary glaucoma prior to the PK.

The phenotype associated with changes in the ZEB1 gene exhibits variable expression and incomplete penetrance and seems to have a low risk for secondary glaucoma or the need for keratoplasty compared to PPCD linked to 20p11.2. There is insufficient data for phenotype correlations with PPCD caused by other genes.