Impact of ADPKD-associated PKD1 gene variants on the human facial phenotype objectified by 3D geometric morphometry

AimVerification and visualization of the possible impact of PKD1 causative variants on facial phenotype using three-dimensional (3D) geometric morphometry.Material and MethodsThree-dimensional facial scans of 39 adult patients with autosomal dominant polycystic kidney disease (ADPKD) and 39 healthy controls were obtained. The 3D facial scans were processed, and analyses were performed using geometric morphometry.ResultsIn 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 zygomatic 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 important 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 showed distinct phenotypic patterns in the forehead, philtrum, and chin.Conclusion: Our findings suggest the presence of specific facial phenotypic traits in ADPKD patients carrying pathogenic PKD1 variants.