We herein report a 3-year-old boy presented with chronic kidney disease (CKD) due to PAX2 missense mutation (C to G transversion at position 418 in exon 4).
He attended our clinic with a 3-month history of foamy urine. Upon examination, he had reduced estimated glomerular filtration rate (GFR) and renal atrophy. Genetic investigations revealed that he has inherited a mutated PAX2 gene from his father, who had renal failure at the age of 20. We searched the literature and confirmed that this mutation site has not been reported by any other group before.
Although renal coloboma syndrome (RCS) with simultaneous kidney and eye involvement is the most common phenotype of PAX2 mutations, current literature supports that such mutations may have profuse clinical manifestations and renal hypoplasia is one distinct entity in the spectrum.

Papillorenal syndrome (PRS), an autosomal dominant inherited condition, is clinically featured by renal hypoplasia and optic nerve dysplasia. Based on current knowledge of genotype-phenotype correlations in PRS, mutations in the Paired box 2 (PAX2) gene have been recognized as a critical pathogenesis of typical renal and optic disease manifestations. However, little information is currently available on the skeletal abnormalities of PRS and the potential contribution of PAX2 mutations. Here, we present a case of a 10-year-old female PRS patient with the typical features of chronic renal failure and severe myopia, but was unexpectedly discovered camptodactyly of her left middle finger which affects the proximal interphalangeal joint. Pathologically, the camptodactyly was further indicated by radiology as a skeletal deformity, demonstrating a decline of bone mineral density and disappearance of joint space. Molecular diagnostics revealed a heterozygous mutation, 220_225dup, in the exon 3 of her PAX2 gene, which is de novo considering the lack of this mutation in her non-consanguineous parents. This mutation leads to duplication of glutamic acid at position 74 and tyrosine at position 75 in PAX2 protein, which may influence the DNA-binding function. Besides, the absence of Spalt like transcription factor 4 (SALL4) mutation excluded the diagnosis of acro-renal-ocular syndrome (AROS), of which clinical characteristics are similar to our patient\'s. This case unravels a previously unrecognized phenotype of camptodactyly due to a significant skeletal deformity of PRS with a heterogeneous PAX2 mutation of hexanucleotide duplication. This report challenges against the current belief of genotype-phenotype correlations in PRS.

Renal coloboma syndrome (RCS) is a rare inherited condition exhibiting a variable clinical phenotype of renal and ocular abnormalities. In 50% of cases, mutations can be found in the transcription factor PAX2. We present three generations of a family with a PAX2 mutation who showed variable eye and renal phenotypes. Renal phenotypes ranged from normal kidneys with the absence of proteinuria to end-stage renal disease (ESRD) at 17 years of age. Eye phenotypes included the typical morning glory anomaly, macular retinal pigment epithelial changes and retinal venous tortuosity. We identified a PAX2 mutation c.228_251dup [p.Ser77_Gly84dup] which segregated with the phenotype in an autosomal dominant fashion. A molecular genetic diagnosis allowed identification and management of at-risk family members. Given the phenotypic variability, clinicians need to consider the possibility of RCS in patients with a family history of chronic kidney disease (CKD) or eye disease.