Diverse phenotypes in children with PAX2-related disorder

Mol Genet Genomic Med. 2019 Jun;7(6):e701. doi: 10.1002/mgg3.701. Epub 2019 May 6.


Background: The aim of this study was to analyze the diverse phenotypes of children with PAX2-related disorder so as to improve our understanding of this disease.

Methods: The clinical data of ten children with PAX2 mutations, detected by targeted region capture sequencing or whole-exome sequencing, were retrospectively analyzed. Family members of index cases were verified by Sanger sequencing and family segregation analysis was performed.

Results: The age of first symptom of 10 unrelated children (six girls and four boys) was 6.4 (ranged from postnatal day to 14.8) years old. Proteinuria, abnormal renal function, and structure were found in all patients. Renal hypoplasia and renal cysts were found in 10 of 10 and five of 10 cases, respectively. Three patients progressed to chronic kidney disease stage 5 and the onset age of end-stage renal disease was 9.8-16.4 years old. PAX2-related ocular abnormalities were found in five of seven cases and three patients were observed to have more than one ocular findings involved. In addition to diverse renal and ocular findings, new phenotypes including congenital ventricular septal defect, skeletal deformity (fourth metatarsal microsomia), ovarian teratoma, and relatively rare extrarenal manifestations such as growth retardation, gout, and microcephaly were also found. Three novel mutations were reported for the first time. De novo mutations occurred in all patients who were carried out segregation analysis. Patients with the same mutation had different manifestations. PAX2-related disorder showed remarkable clinical variability and phenotypic heterogeneity.

Conclusion: We firstly reported skeletal deformity (fourth metatarsal microsomia), ovarian teratoma, and congenital ventricular septal defect as new phenotypes of PAX2-related disorder which enlarged the phenotypic spectrum. Gout was firstly reported as the onset symptom of PAX2-related disorder. The diagnosis of PAX2-related disorder should be considered without family history due to a much higher percentage of De novo mutations.

Keywords: PAX2 gene; children; new phenotypes; renal coloboma syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Coloboma / genetics*
  • Coloboma / pathology
  • Female
  • Humans
  • Male
  • Mutation
  • PAX2 Transcription Factor / genetics*
  • Phenotype*
  • Renal Insufficiency / genetics*
  • Renal Insufficiency / pathology
  • Vesico-Ureteral Reflux / genetics*
  • Vesico-Ureteral Reflux / pathology


  • PAX2 Transcription Factor
  • PAX2 protein, human

Supplementary concepts

  • Papillorenal syndrome