Impact of adpkd-associated PKD1 gene variants on the human facial phenotype quantified by 3d geometric morphometry

Abstract

Verification and visualization of the possible impact of PKD1 causative variants associated with autosomal dominant polycystic kidney disease (ADPKD) on facial phenotype using three-dimensional (3D) geometric morphometry. Three-dimensional facial scans of 39 adult patients with ADPKD were obtained, together with 3D scans of 39 sex and age matched healthy individuals. The 3D facial scans were processed, and morphometric analyses were performed using geometric morphometry to quantified potential phenotypical traits in ADPKD patients. In ADPKD patients, we observed several statistically significant differences in facial morphology compared with healthy controls. In both sexes, considerable retrusion of the supraorbital arches and, conversely, prominence of the suborbital region were detected. In males, additional retrusion along the entire midline was observed, with significant changes at the nasal tip and chin. In females, the midline showed a tendency toward prominence, although these differences were not significant compared with controls. Asymmetry analysis revealed that males with ADPKD exhibit less pronounced asymmetry, with an asymmetry pattern very similar to that of controls. In contrast, females with ADPKD differ from controls in the midface and lower face, showing laterally reversed asymmetry deviations. Patients in the truncating variant group and non-truncating variant groups showed distinct phenotypic patterns in the forehead, philtrum, and chin areas. Our findings suggest the presence of distinct facial phenotypic traits in ADPKD patients carrying pathogenic PKD1 variants compared with healthy controls. In addition, we observed partial subgroup-specific differences according to sex and mutation type.