Yellow Nail Syndrome in Childhood: A Case Report Highlighting Diagnostic Challenges and the Possible Role of Nail Development-Related Genetic Variants.
Introduction Yellow nail syndrome (YNS) is a rare disorder characterized by the triad of yellow nail discoloration, lymphedema, and respiratory manifestations. Pediatric cases are uncommon and often present incompletely, making diagnosis challenging. Although generally considered acquired, rare familial cases suggest possible genetic susceptibility. Case Presentation An 8-year-old girl presented with diffuse yellow nail dystrophy involving all 20 nails and recurrent unilateral swelling of the left lower extremity. Examination revealed yellow discoloration, dystrophy, and cuticle loss affecting all nails. Extensive multidisciplinary evaluation showed no systemic or respiratory involvement. Nail histopathology demonstrated dense bacterial aggregates resembling biofilm beneath the nail plate, while fungal studies were negative. Genetic analysis identified a heterozygous variant of uncertain significance in the FZD6 gene, associated with nail morphogenesis, whereas FOXC2 mutation analysis was negative. Conservative treatment with lymphedema exercises, compression bandaging, and topical therapy resulted in clinical improvement. Conclusion This case highlights the diagnostic difficulty of pediatric YNS in the absence of the complete classical triad. YNS should remain in the differential diagnosis of children with unexplained nail dystrophy and recurrent extremity edema, even when systemic and genetic evaluations are inconclusive.