Denys-Drash Syndrome

A disorder of sex development characterized by UROGENITAL ABNORMALITIES; GONADAL DYSGENESIS; and WILMS TUMOR. It is caused by a mutation in the Wilms tumor suppressor gene (GENES, WILMS TUMOR) on chromosome 11.

Also Known As:

Networked: 66 relevant articles (2 outcomes, 1 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Wilms Tumor (Wilm's Tumor)
2.	XY Disorders of Sex Development 46 (Male Pseudohermaphroditism)
3.	Disorders of Sex Development (Intersexuality)
4.	Nephrotic Syndrome (Syndrome, Nephrotic)
5.	Renal Insufficiency (Renal Failure)

Experts

1.	Bates, David O: 2 articles (12/2009 - 10/2009)
2.	Harper, Steven J: 2 articles (12/2009 - 10/2009)
3.	Fleming, Stewart: 2 articles (06/2008 - 09/2003)
4.	Hooper, Martin L: 2 articles (06/2008 - 09/2003)
5.	Patek, Charles E: 2 articles (06/2008 - 09/2003)
6.	Miles, Colin G: 2 articles (06/2008 - 09/2003)
7.	Royer-Pokora, Brigitte: 2 articles (03/2007 - 06/2004)
8.	Denamur, E: 2 articles (08/2001 - 05/2000)
9.	Lim, Jae Young: 1 article (06/2014)
10.	Woo, Hyang-Ok: 1 article (06/2014)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Denys-Drash Syndrome:

1.	Cyclosporine (Ciclosporin)FDA LinkGeneric 03/01/2011 - "In this report, we present a patient with Denys-Drash syndrome, in whom the cyclosporine A (CsA) was found to induce total remission. "
2.	diffuse Mesangial sclerosisIBA 11/01/2006 - "Germline WT1 missense mutations located in exons 8 or 9 coding for zinc fingers 2 or 3 have been detected in nearly all patients with Denys-Drash syndrome and in some patients with isolated diffuse mesangial sclerosis. " 09/01/2004 - "While diffuse mesangial sclerosis is traditionally described as being the glomerulopathy of Denys-Drash syndrome (DDS), the podocyte proliferative lesions may be overlooked in these DDS cases. " 01/01/2003 - "The findings of the renal biopsy showed diffuse mesangial sclerosis, consistent with the characteristic change in Denys-Drash syndrome. " 03/01/2001 - "Diffuse mesangial sclerosis is a rare renal disease, occurring either in isolation or as part of Denys-Drash syndrome. " 05/01/2000 - "Absence of correlation between genotype and the severity of diffuse mesangial sclerosis in Denys-Drash syndrome."
3.	DNA (Deoxyribonucleic Acid)IBA 09/17/1996 - "These results suggest that the clinical phenotype of Denys-Drash syndrome can be associated with a modest reduction in the DNA binding affinity of WT1." 03/16/1995 - "Because the most common mutation associated with Denys-Drash Syndrome disrupts the zinc finger domains of WT1, the results also suggest that the mutant WT1 may have aberrant DNA binding activity and perhaps function as a dominant negative effector of wt WT1." 07/01/1993 - "Deletions of the WT1 gene or point mutations which destroy the DNA binding activity of the protein are associated with the development of the pediatric nephroblastoma Wilms tumor and Denys-Drash syndrome. " 02/20/2001 - "Point mutations in the zinc fingers associated with Denys-Drash syndrome have dramatically different effects on the interaction of WT1-ZFP with DNA, but a consistent and modest effect on the interaction with RNA. " 03/01/1995 - "DNA binding capacity of the WT1 protein is abolished by Denys-Drash syndrome WT1 point mutations."
4.	WT1 ProteinsIBA 05/18/2001 - "Mutant WT1 proteins in Denys-Drash syndrome patients were unable to activate this promoter. " 10/01/1999 - "The N- and C-terminal domains of WT1 also exhibited partial repression, as did the most common mutant version of the WT1 protein associated with Denys-Drash syndrome. " 03/01/1995 - "DNA binding capacity of the WT1 protein is abolished by Denys-Drash syndrome WT1 point mutations." 09/17/1996 - "A number of point mutations in the zinc finger domain of the Wilms' tumor suppressor protein WT1 have been isolated from the DNA of patients with Denys-Drash syndrome, an association of Wilms' tumor, nephropathy, and genital anomalies. " 09/17/1996 - "Effects of Denys-Drash syndrome point mutations on the DNA binding activity of the Wilms' tumor suppressor protein WT1."
5.	Nonsense Codon (Nonsense Mutation)IBA 08/01/2011 - "A novel WT1 heterozygous nonsense mutation (p.K248X) causing a mild and slightly progressive nephropathy in a 46,XY patient with Denys-Drash syndrome." 06/15/2004 - "Patients with the two most frequent nonsense mutations R362X and R390X and the Denys-Drash syndrome (DDS) hot spot mutation R394W/Q/L had a very early onset (9, 12, and 18 mo, respectively). " 01/01/2013 - "Mutation analysis of WT1 identified two single-nucleotide polymorphisms, one recurrent nonsense mutation (p.R458X) in a patient with proteinuria but without genitourinary findings of Denys-Drash syndrome (DDS) and one novel missense mutation, p.C428Y, in a patient with Denys-Drash syndrome phenotype. " 02/01/2008 - "We present a new case of Denys-Drash syndrome in a patient initially diagnosed with XY ambiguous genitalia/partial androgen insensitivity syndrome, who was found to have a novel nonsense mutation in exon 6 leading to a stop codon and hence a truncated protein. "
6.	Vascular Endothelial Growth Factor A (Vascular Endothelial Growth Factor)IBA 06/01/2007 - "Regulation of VEGF by WT1 likely contributes to kidney angiogenesis during development and WT1 mutants such as DDS(R384W) are associated with the Denys-Drash syndrome (DDS), characterized by renal abnormalities. " 11/01/2012 - "The role of VEGF 165b has not been investigated in as much detail as VEGF 165, although it appears to be highly expressed in non-angiogenic tissues and, in contrast with VEGF 165, is downregulated in tumors and other pathologies associated with abnormal neovascularization such as diabetic retinopathy or Denys Drash syndrome. " 12/01/2009 - "Anti-angiogenic VEGF (vascular endothelial growth factor) isoforms, generated from differential splicing of exon 8, are widely expressed in normal human tissues but down-regulated in cancers and other pathologies associated with abnormal angiogenesis (cancer, diabetic retinopathy, retinal vein occlusion, the Denys-Drash syndrome and pre-eclampsia). "
7.	Protein Isoforms (Isoforms)IBA 11/01/1993 - "Further evidence that imbalance of WT1 isoforms may be involved in Denys-Drash syndrome." 10/01/2009 - "The distally spliced antiangiogenic isoforms are expressed in normal human tissue, but downregulated in angiogenic diseases, such as cancer and proliferative retinopathy, and in developmental pathologies, such as Denys Drash syndrome and preeclampsia. " 12/01/2009 - "Anti-angiogenic VEGF (vascular endothelial growth factor) isoforms, generated from differential splicing of exon 8, are widely expressed in normal human tissues but down-regulated in cancers and other pathologies associated with abnormal angiogenesis (cancer, diabetic retinopathy, retinal vein occlusion, the Denys-Drash syndrome and pre-eclampsia). "
8.	Transcription Factors (Transcription Factor)IBA 03/01/1996 - "Mutations in transcription factors have recently been identified in a number of genetic diseases (for example, Denys-Drash syndrome, WT1 [19]; pituitary dwarfism, PIT1 [16]; Rubinstein-Taybi syndrome, CBP [20]. " 04/01/1998 - "Constitutional mutations of the WT1 gene, encoding a zinc-finger transcription factor involved in renal and gonadal development, are found in most patients with Denys-Drash syndrome (DDS), or diffuse mesangial sclerosis (DMS) associated with pseudohermaphroditism and/or Wilms tumor (WT). "
9.	Proteins (Proteins, Gene)IBA 11/01/1996 - "Analyses of WT1 mutations in individuals with WT-associated Drash syndrome and WT patients with GU anomalies in the absence of Drash syndrome indicate that Drash patients almost invariably carry germline missense mutations in the zinc finger domains whereas WT/GU patients carry germline mutations that delete the WT1 gene or encode truncated proteins. " 03/01/1999 - "We show that two WT1-interacting proteins, the product of a Denys-Drash syndrome allele of wt1 and prostate apoptosis response-4 protein, inhibit WT1-mediated transactivation of Dax-1. "
10.	Galloway Mowat syndromeIBA 10/01/2000 - "Associated conditions included incomplete Drash syndrome (n=1), Galloway-Mowat syndrome (n=1), and severe mental and motor retardation of unknown origin (n=3). " 05/01/2012 - "DMS is a phenotypic expression of syndromic entities such as WAGR syndrome (Wilms' tumor, aniridia, genitourinary anomalies and mental retardation), Denys Drash syndrome, Pierson syndrome, Frasier syndrome, or Galloway-Mowat syndrome. "

Therapies and Procedures

1.	Kidney Transplantation 06/01/1998 - "Renal transplantation in the management of bilateral Wilms' tumour (BWT) and of Denys-Drash syndrome (DDS)." 06/01/2005 - "Current practices in children with Wilms' tumor and Denys-Drash syndrome appear to be on target to portend good outcome following renal transplantation." 06/01/1998 - "We previously reported the case of a patient affected with Denys-Drash syndrome (DDS), who developed disseminated EBV-related Burkitt's lymphoma (BL) after kidney transplantation. " 03/01/1997 - "Disseminated Burkitt's lymphoma after kidney transplantation: a case report in a boy with Drash syndrome." 06/01/2005 - "Outcome of renal transplantation for Wilms' tumor and Denys-Drash syndrome: a report of the North American Pediatric Renal Transplant Cooperative Study."
2.	Transplants (Transplant) 06/01/2005 - "The North American Pediatric Renal Transplant Cooperative Study dialysis (1992-2001) and transplant registries (1987-2002) were analyzed, comparing children 0-18 yr old with Wilms' tumor and Denys-Drash syndrome to other primary diagnoses. " 06/01/2005 - "In conclusion, most children dialyzed because of Wilms' tumor and Denys-Drash syndrome who did not receive a renal transplant died of Wilms' tumor. " 06/01/2005 - "The transplant registry included 43 children with Wilms' tumor, 43 children with Denys-Drash syndrome, and 7469 patients with other diagnoses. " 06/01/2005 - "Of these, 10 children with Wilms' tumor and three with Denys-Drash syndrome did not receive a renal transplant and all died. " 06/01/2005 - "Outcome of renal transplantation for Wilms' tumor and Denys-Drash syndrome: a report of the North American Pediatric Renal Transplant Cooperative Study."
3.	Nephrectomy 01/01/2003 - "[A case of Denys-Drash syndrome with prophylactic bilateral nephrectomy]." 06/01/1998 - "In Denys-Drash syndrome (DDS), bilateral nephrectomy is indicated both because of the associated nephropathy usually progressing rapidly to end-stage renal failure and because of the high risk of WT development in any residual renal tissue. " 07/01/2011 - "One patient (4%) died 17.75 years after diagnosis, five (20%) had renal transplants: 3/5 after bilateral nephrectomy for Denys-Drash syndrome (DDS), and 2/5 for ESRD after an interval of 7 and 18 years, respectively. " 06/01/2006 - "Indications for surgery were: renal function <9% in cases of unilateral nephrectomy; the prevention of renal neoplastic changes in the patient with Denys-Drash syndrome; symptomatic large renal cysts; and suspected lymphoma not diagnosed with a previous percutaneous biopsy. " 06/01/2006 - "Twenty-seven patients underwent unilateral retroperitoneal nephrectomy; 1 child with Denis Drash syndrome underwent transperitoneal bilateral nephrectomy; 2 children underwent renal cyst unroofing; and 1 child with lymphoma underwent retroperitoneal laparoscopic renal biopsy. "
4.	Transplantation (Transplant Recipients) 12/01/2002 - "Wilms tumor in a pediatric renal transplant recipient with unexpected Denys-Drash syndrome." 06/01/1999 - "Unexpected Wilms' tumor in a pediatric renal transplant recipient: suspected Denys-Drash syndrome." 06/01/2005 - "However, the outcomes of children with Wilms' tumor and Denys-Drash syndrome who proceeded to renal transplantation are comparable with children with other diagnoses, with no graft failures because of recurrence and only one death from Wilms' tumor in a Wilms' patient who received only a short course of dialysis prior to transplantation. " 03/01/1997 - "A 6-year-old boy with Drash syndrome developed disseminated Burkitt's lymphoma 38 months after transplantation for renal failure. " 02/27/1994 - "(The risk ratio for ATN was 3.1 [P < 0.001] and for GF30 it was 6.4 [P < 0.001].) Mortality after transplantation was also affected by the underlying renal disease, with high mortality rates observed for oxalosis (n = 21, 33.3%), congenital nephrotic syndrome (n = 79, 15.2%), pyelo/interstitial nephritis (n = 54, 11.1%), and Drash syndrome (n = 14, 21.4%). "
5.	Embolectomy 05/01/2012 - "We report a 5-year-old male with Denys-Drash syndrome who rapidly developed Wilms tumor with vascular invasion, subsequent saddle tumor embolus, and required emergent embolectomy. " 05/01/2012 - "This case illustrates the rapid emergence of Wilms tumor in a patient with Denys-Drash syndrome and the importance of considering embolectomy over thrombolytic therapy for PE in this population, given a high likelihood of tumor embolus."