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:

Nephropathy, Wilms Tumor, and Genital Anomalies; Pseudohermaphroditism, Nephron Disorder and Wilms' Tumor; Wilms Tumor and Pseudohermaphroditism; Denys Drash Syndrome; Syndrome, Denys-Drash; Syndrome, Drash; Drash Syndrome

Networked: 65 relevant articles (2 outcomes, 1 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Wilms Tumor (Wilm's Tumor)
2.	Neoplasms (Cancer)
3.	Renal Insufficiency (Renal Failure)
4.	Disorders of Sex Development (Intersexuality)
5.	Chronic Kidney Failure (Chronic Renal Failure)

Experts

1.	Oltean, Sebastian: 2 articles (02/2018 - 12/2009)
2.	Cheng, Xiaodong: 2 articles (01/2018 - 12/2016)
3.	Zhang, Xing: 2 articles (01/2018 - 12/2016)
4.	Zheng, Yu: 2 articles (01/2018 - 12/2016)
5.	Bates, David O: 2 articles (12/2009 - 10/2009)
6.	Harper, Steven J: 2 articles (12/2009 - 10/2009)
7.	Akramov, Nail R: 1 article (05/2021)
8.	Osipova, Ilsiya V: 1 article (05/2021)
9.	Shavaliev, Rafael F: 1 article (05/2021)
10.	Albanese, Federica: 1 article (01/2021)

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.	Proteins (Proteins, Gene)FDA Link 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. " 12/01/2016 - "In line with these findings, the abundance of Cmip was early and significantly increased at the transcript and protein level in podocytes displaying a primary defect in Wt1, including Denys-Drash syndrome and Frasier syndrome. " 06/01/2008 - "Effects on kidney disease, fertility and development in mice inheriting a protein-truncating Denys-Drash syndrome allele (Wt1tmT396)." 05/14/2021 - "Pediatric patients with WTl-associated syndromes (including Wilms' tumor-aniridia syndrome and Denys-Drash syndrome), Perlman syndrome, mosaic aneuploidy, and Fanconi anemia with a biallelic breast cancer type 2 susceptibility protein mutation have the highest risk of developing Wilms' tumor. " 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. "
3.	DNA (Deoxyribonucleic Acid)IBA 02/01/2019 - "Mutations on its DNA recognition domain could lead to Denys-Drash syndrome, and alternate splicing results in insertion of the tripeptide Lys-Thr-Ser (KTS) between the third and fourth zinc fingers (ZFs), leading to changes in the DNA-binding function. " 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." 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.	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. " 02/15/2018 - "Dysregulation of the VEGF-Axxx/VEGF-Axxxb isoform balance has recently been reported in several kidney pathologies, including diabetic nephropathy (DN) and 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). "
5.	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."
6.	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. " 02/15/2018 - "Dysregulation of the VEGF-Axxx/VEGF-Axxxb isoform balance has recently been reported in several kidney pathologies, including diabetic nephropathy (DN) and 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.	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. "
8.	Transcription Factors (Transcription Factor)IBA 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). " 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]. "
9.	ErbB Receptors (EGF Receptor)IBA 09/01/1997 - "Regulation of renal EGF receptor expression is normal in Denys-Drash syndrome."
10.	Anti-Mullerian HormoneIBA 06/01/2014 - "Denys-Drash syndrome, septated vagina and low level of anti-Mullerian hormone in male neonate."

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." 06/01/2005 - "Outcome of renal transplantation for Wilms' tumor and Denys-Drash syndrome: a report of the North American Pediatric Renal Transplant Cooperative Study." 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."
2.	Nephrectomy 01/01/2003 - "[A case of Denys-Drash syndrome with prophylactic bilateral nephrectomy]." 01/01/2020 - "The possibility of hypotension after nephrectomy should be considered in patients with Denys-Drash syndrome." 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. " 06/01/1998 - "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. " 08/12/2023 - "Prophylactic bilateral nephrectomy and preemptive kidney transplantation for Denys-Drash syndrome prior to development of kidney failure."
3.	Transplantation 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. " 01/01/2021 - "The underlying diseases leading to transplantation were biliary atresia, polycystic kidney, and Denys-Drash syndrome. " 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%). "
4.	Drug Therapy (Chemotherapy) 10/01/2019 - "The remaining five patients included the following: two with unilateral WT (resected before chemotherapy), two with bilateral WT (resected after neoadjuvant chemotherapy), and one with Denys-Drash syndrome, end-stage renal disease, and history of WT in the contralateral kidney. " 04/01/1995 - "Renal failure with nephroblastoma is uncommon and is usually either a manifestation of the Drash syndrome or a complication of chemotherapy. " 09/01/2020 - "A treatment-sparing approach was adopted for 6 patients with severe intellectual impairment to minimize toxicity: a child with postpartum asphyxia and medulloblastoma did not receive radiotherapy; 1 patient with mitochondrial encephalopathy and a testicular germ cell tumor did not receive bleomycin and lung metastasectomy; 2 patients (1 with Down + West syndrome + Wilms tumor (WT) and 1 with Denys-Drash syndrome + WT) did not receive vincristine; 1 child with corpus callosum agenesis and anaplastic ependymoma did not receive chemotherapy; 1 child with structural chromosomal aberrations and a primitive neuro-ectodermal tumor received personalized chemotherapy. "
5.	Metastasectomy 09/01/2020 - "A treatment-sparing approach was adopted for 6 patients with severe intellectual impairment to minimize toxicity: a child with postpartum asphyxia and medulloblastoma did not receive radiotherapy; 1 patient with mitochondrial encephalopathy and a testicular germ cell tumor did not receive bleomycin and lung metastasectomy; 2 patients (1 with Down + West syndrome + Wilms tumor (WT) and 1 with Denys-Drash syndrome + WT) did not receive vincristine; 1 child with corpus callosum agenesis and anaplastic ependymoma did not receive chemotherapy; 1 child with structural chromosomal aberrations and a primitive neuro-ectodermal tumor received personalized chemotherapy. "