A novel ZEB1 splice-site variant causing early-onset type 3 posterior polymorphous corneal dystrophy and suspected...

Posterior polymorphous corneal dystrophy type 3 (PPCD3) is an autosomal dominant endothelial dystrophy caused by variations in the ZEB1 gene. We report a pediatric case presenting with progressive visual impairment associated with simultaneous features of corneal ectasia and endothelial dystrophy. A 9-year-old boy presented with progressive diminution of vision and high myopia. Slit-lamp examination revealed prominent corneal nerves, and central corneal steepening, along with diffuse endothelial guttae and a beaten-metal appearance of the endothelium. Multimodal imaging including Scheimpflug tomography that demonstrated marked bilateral corneal steepening with tomographic features suggestive of corneal ectasia (Kmax 59.0 D in the right eye and 61.6 D in the left eye). Interestingly, central corneal thickness was increased (636 µm in the right eye and 659 µm in the left eye), feature atypical of keratoconus. Specular microscopy demonstrated reduced endothelial cell density. Whole-exome sequencing of the proband identified a novel heterozygous splice-site variant in ZEB1 (chr10:g.31510671A > T; c.485-2A > T), affecting the canonical 3' splice acceptor site. Targeted next-generation sequencing of parental blood samples confirmed the variant in the father (heterozygous) and its absence in mother, consistent with paternal inheritance. This case provides additional evidence supporting the recognized association between ZEB1-related PPCD3 and suspected corneal ectasia, while describing a novel splice-site ZEB1 variant.