Wnt/Planar Cell Polarity Impairment and the Genetics of Yellow Nail Syndrome

Yellow nail syndrome (YNS) is a rare disorder with unclear etiology, characterized by yellow nails, lymphedema, and chronic lung disease. In a study of 11 patients, researchers identified bi-allelic variants in the Wnt/planar cell polarity (PCP) pathway genes CELSR1 or FZD6 in all six congenital YNS (cYNS) patients, but not in the five sporadic YNS (sYNS) patients. This suggests a genetic cause for cYNS, with defects in planar cell polarity organization playing a significant role in YNS pathogenesis. The study found reduced expression of Wnt/PCP-related genes in cYNS patients, providing a new understanding of YNS and potential exploration of the Wnt/PCP pathway in similar disorders.