Researchers have identified defects in the planar cell polarity (PCP) pathway as a significant factor in Yellow Nail Syndrome (YNS), particularly its congenital form. A study published in the Annals of Internal Medicine presents the first genetic explanation for the disease, linking disruptions in the PCP pathway to its development. YNS is characterized by symptoms such as yellow, thickened nails; lymphedema; and chronic lung disease. The study analyzed genetic data from patients, revealing that most with congenital YNS (cYNS) exhibited abnormalities in the CELSR1 gene, which has autosomal recessive inheritance. In this cohort, symptoms appeared either prenatally or shortly after birth. Patients with sporadic YNS (sYNS) showed no significant variants in CELSR1 or related genes. The researchers found that the Wnt/PCP signaling pathway was disrupted in cYNS patients and, to a lesser extent, in sYNS patients without genetic defects. These findings underscore the critical role of the Wnt/PCP pathway in the pathogenesis of YNS and may lead to a better understanding and potential therapeutic strategies for this rare condition.
