title: [Clinical and pathological features of Denys-Drash syndrome: report of 3 cases].
abstract: OBJECTIVE
  To study the clinical and pathological features of Denys-Drash syndrome (DDS).
  
  
  METHODS
  Three DDS cases who were treated in our department from December 2009 to June 2011 were subjected to this study by reviewing of literature.
  
  
  RESULTS
  Both case 1 and case 2 were female, with karyotype 46, XX. Case 3 was male with bilateral cryptorchidism. The ages of nephropathy onset of the three cases were 1 year and 9 months, 2 years and 8 moths, and 3 months respectively. Proteinuria in case 2 and case 3 were evidenced to be resistant to steroid. Case 1 was partially responsive to tacrolimus, plasma albumin and cholesterol were improved, although proteinuria was persistent after Tacrolimus was administered. Remission was achieved in case 2 after administration of cyclosporine A and later tacrolimus, and her renal function remains normal till present (4 years and 9 months). Residue renal histology revealed diffused mesangial sclerosis (DMS) in all three patients. All of the three patients had developed right unilateral Wilms tumor. A novel WT1 missense mutation exon 9 c.1213C > G was detected in case 1. WT1 exon 9 c.1168C > T nonsense mutation and exon 8 c.1130A > T missense mutation were detected in case 2 and case 3, respectively.
  
  
  CONCLUSIONS
  The clinical manifestation of nephropathy in DDS is variable. The majority present with early onset nephropathy and reach renal failure before the age of 4 years. But in a few patients, nephropathy can also be present much later and progress slowly. Proteinuria in DDS is resistant to steroid but is responsive to calcineurin inhibitors, including Cyclosporine A. The effectiveness of tacrolimus was also observed in this study. DDS is evidently caused by WT1 mutation. DMS is the characteristic renal pathological change in DDS.
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Hai-yan
authors.initials: HY
authors.lastname: Wang
authors.forename: Liang-zhong
authors.initials: LZ
authors.lastname: Sun
authors.forename: Zhi-hui
authors.initials: ZH
authors.lastname: Yue
authors.forename: Juan
authors.initials: J
authors.lastname: Yang
authors.forename: Xiao-yun
authors.initials: XY
authors.lastname: Jiang
authors.forename: Ying
authors.initials: Y
authors.lastname: Mo
mesh_terms: D016572:Cyclosporine / Q000627:therapeutic use; D030321:Denys-Drash Syndrome / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D017809:Fatal Outcome; D005260:Female; D016162:Genes, Wilms Tumor; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D009404:Nephrotic Syndrome / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D011507:Proteinuria / Q000188:drug therapy; D012598:Sclerosis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D016559:Tacrolimus / Q000627:therapeutic use; D016896:Treatment Outcome; D025721:WT1 Proteins / Q000235:genetics; D009396:Wilms Tumor / Q000188:drug therapy / Q000235:genetics / Q000473:pathology
chemical_list: D025721:WT1 Proteins; D016572:Cyclosporine; D016559:Tacrolimus