MCID: DNY001
MIFTS: 53

Denys-Drash Syndrome malady

Categories: Genetic diseases, Rare diseases, Nephrological diseases, Reproductive diseases, Endocrine diseases, Fetal diseases, Cancer diseases

Aliases & Classifications for Denys-Drash Syndrome

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Sources:
49OMIM, 32LifeMap Discovery®, 10Disease Ontology, 11diseasecard, 45NIH Rare Diseases, 22GeneTests, 23Genetics Home Reference, 47Novoseek, 12DISEASES, 51Orphanet, 67UniProtKB/Swiss-Prot, 36MeSH, 65UMLS, 24GTR, 42NCIt, 59SNOMED-CT, 28ICD10 via Orphanet, 37MESH via Orphanet, 66UMLS via Orphanet, 34MedGen, 61The Human Phenotype Ontology
See all MalaCards sources

Aliases & Descriptions for Denys-Drash Syndrome:

Name: Denys-Drash Syndrome 49 32 10 11 45 22 23 47 12 51 67 36 65
Drash Syndrome 45 22 23 51 24
Wilms Tumor and Pseudohermaphroditism 45 22 23 51
Nephropathy, Wilms Tumor, and Genital Anomalies 45 23
 
Dds 23 67
Nephropathy Associated with Male Pseudohermaphroditism and Wilms' Tumor 45
Pseudohermaphroditism, Nephron Disorder and Wilms' Tumor 45

Characteristics:

Orphanet epidemiological data:

51
denys-drash syndrome:
Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal

HPO:

61
denys-drash syndrome:
Inheritance: somatic mutation, autosomal dominant inheritance


Classifications:



External Ids:

OMIM49 194080
Disease Ontology10 DOID:3764
MeSH36 D030321
NCIt42 C84668
Orphanet51 220
SNOMED-CT59 236385009
ICD10 via Orphanet28 N04.1
MESH via Orphanet37 D030321
UMLS via Orphanet66 C0950121
MedGen34 C0950121
UMLS65 C0950121

Summaries for Denys-Drash Syndrome

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NIH Rare Diseases:45 Denys-drash syndrome is a condition that affects the kidneys and genitalia. kidney disease typically begins in the first few months of life, often leading to kidney failure in childhood. in addition, up to 90 percent of people with this condition develop a rare form of kidney cancer known as wilms tumor. males with denys-drash syndrome have gonadal dysgenesis, a condition in which the external genitalia do not look clearly male or clearly female (ambiguous genitalia) or the genitalia appear to be completely female. the testes are also undescended, meaning that they remain in the pelvis, abdomen, or groin. affected females usually have normal genitalia. for this reason, females with this condition may be diagnosed with isolated nephrotic syndrome. denys-drash syndrome is caused by mutations in the wt1 gene. this condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. however, most cases result from new mutations in the gene and occur in people with no history of the disorder in their family. last updated: 10/28/2013

MalaCards based summary: Denys-Drash Syndrome, also known as drash syndrome, is related to dentin dysplasia, type ii and diastrophic dysplasia, and has symptoms including nephroblastoma (wilms tumor), nephropathy and nephrotic syndrome. An important gene associated with Denys-Drash Syndrome is WT1 (Wilms Tumor 1), and among its related pathways are Neural Stem Cell Differentiation Pathways and Lineage-specific Markers and Nephrin/Neph1 signaling in the kidney podocyte. Affiliated tissues include kidney, testes and prostate, and related mouse phenotypes are embryo and renal/urinary system.

Disease Ontology:10 An autosomal dominant disease that is characterized by the association of diffuse mesangial sclerosis (DMS), male pseudohermaphroditism with a 46,XY karyotype, and nephroblastoma that derives from an abnormality in the WT1 gene (Wilms' tumor suppressor gene).

UniProtKB/Swiss-Prot:67 Denys-Drash syndrome: Typical nephropathy characterized by diffuse mesangial sclerosis, genital abnormalities, and/or Wilms tumor. There is phenotypic overlap with WAGR syndrome and Frasier syndrome. Inheritance is autosomal dominant, but most cases are sporadic.

Genetics Home Reference:23 Denys-Drash syndrome is a condition that affects the kidneys and genitalia.

Wikipedia:68 Denys–Drash syndrome (DDS) or Drash syndrome is a rare disorder or syndrome characterized by gonadal... more...

Description from OMIM:49 194080

Related Diseases for Denys-Drash Syndrome

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Diseases related to Denys-Drash Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50)    (show all 82)
idRelated DiseaseScoreTop Affiliating Genes
1dentin dysplasia, type ii11.0
2diastrophic dysplasia11.0
3dentin dysplasia, type i, with microdontia and misshapen teeth11.0
4mohr-tranebjaerg syndrome11.0
5darier disease10.9
6dentin dysplasia10.9
7nephrogenic adenofibroma10.5PAX2, WT1
8gastroesophageal junction adenocarcinoma10.4PAX2, WT1
9liver sarcoma10.4PAX2, WT1
10breast pericanalicular fibroadenoma10.4PAX2, WT1
11nephrotic syndrome10.4
12gonadal dysgenesis10.4
13frasier syndrome10.3
14muscular dystrophy-dystroglycanopathy , type a, 110.3CD2AP, PAX2
15ovarian gonadoblastoma10.3NR5A1, WT1
16autosomal recessive myogenic arthrogryposis multiplex congenita10.3CD2AP, NPHS1
17glomerulosclerosis10.3
18gonadoblastoma10.3
19diffuse mesangial sclerosis10.3
20spastic hemiplegia10.3CD2AP, NPHS1
21hyperuricemia10.2NR5A1, WT1
22epithelial predominant wilms' tumor10.2MECOM, WT1
23pseudohermaphroditism10.2
24lymphoma10.1
25hemolytic-uremic syndrome10.1
26pyloric stenosis10.1
27mixed gonadal dysgenesis10.1
28congenital diaphragmatic hernia10.1
29kidney disease10.1
30septate vagina10.1
31nasopharyngeal carcinoma 210.1CD2AP, NPHS1
32coronary artery disease10.1
33artery disease10.1
34endotheliitis10.1
35diffuse neonatal hemangiomatosis10.0NPHS1, PAX2, WT1
36epidermolysis bullosa dystrophica10.0NPHS1, WT1
37suclg1-related mitochondrial dna depletion syndrome, encephalomyopathic form, with mild methylmalonic aciduria10.0CD2AP, NPHS1, WT1
38congenital nonhemolytic jaundice10.0CD2AP, NPHS1, WT1
39myocardial infarction10.0
40fecal incontinence10.0CD2AP, NPHS1, WT1
41teratocarcinoma10.0SRY, WT1
42dissociative disorder10.0
43coronary artery vasospasm10.0CD2AP, NPHS1, WT1
44leprosy9.9
45anorectal atresia9.9NR5A1, SRY
46dysmorphism-short stature-deafness-disorder of sex development syndrome9.9NR5A1, SRY
47actg2-related disorders9.9NR5A1, SRY
4848,xxxy syndrome9.9NR5A1, SRY
49swyer-james syndrome9.8NR5A1, SRY
50obesity9.8

Graphical network of the top 20 diseases related to Denys-Drash Syndrome:



Diseases related to denys-drash syndrome

Symptoms for Denys-Drash Syndrome

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Symptoms by clinical synopsis from OMIM:

194080

Clinical features from OMIM:

194080

Symptoms:

 51 (show all 7)
  • renal disease/nephropathy
  • nephrotic syndrome
  • proteinuria
  • male pseudohermaphrodism/lack of virilisation
  • nephroblastoma/wilms tumor
  • chronic arterial hypertension
  • mixed gonadal dysgenesis

HPO human phenotypes related to Denys-Drash Syndrome:

(show all 22)
id Description Frequency HPO Source Accession
1 nephroblastoma (wilms tumor) hallmark (90%) HP:0002667
2 nephropathy hallmark (90%) HP:0000112
3 nephrotic syndrome hallmark (90%) HP:0000100
4 proteinuria hallmark (90%) HP:0000093
5 male pseudohermaphroditism hallmark (90%) HP:0000037
6 hypertension typical (50%) HP:0000822
7 gonadal dysgenesis occasional (7.5%) HP:0000133
8 true hermaphroditism HP:0010459
9 stage 5 chronic kidney disease HP:0003774
10 gonadal tissue inappropriate for external genitalia or chromosomal sex HP:0003248
11 nephroblastoma (wilms tumor) HP:0002667
12 diffuse mesangial sclerosis HP:0001967
13 hypertension HP:0000822
14 congenital diaphragmatic hernia HP:0000776
15 ovarian gonadoblastoma HP:0000149
16 gonadal dysgenesis HP:0000133
17 nephropathy HP:0000112
18 nephrotic syndrome HP:0000100
19 focal segmental glomerulosclerosis HP:0000097
20 ambiguous genitalia, female HP:0000061
21 male pseudohermaphroditism HP:0000037
22 ambiguous genitalia, male HP:0000033

Drugs & Therapeutics for Denys-Drash Syndrome

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Interventional clinical trials:

idNameStatusNCT IDPhase
1Registry for Patients With Wilms' Tumor Suppressor Gene 1 (WT1) Mutation Associated DiseasesCompletedNCT01252901

Search NIH Clinical Center for Denys-Drash Syndrome


Cochrane evidence based reviews: denys-drash syndrome

Genetic Tests for Denys-Drash Syndrome

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Genetic tests related to Denys-Drash Syndrome:

id Genetic test Affiliating Genes
1 Denys-Drash Syndrome22 WT1

Anatomical Context for Denys-Drash Syndrome

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MalaCards organs/tissues related to Denys-Drash Syndrome:

33
Kidney, Testes, Prostate, Breast, Liver, Endothelial, T cells

LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database

Cells/anatomical compartments in embryo or adult related to Denys-Drash Syndrome:
id TissueAnatomical CompartmentCell Relevance
1 KidneyMetanephric MesenchymeMetanephric Mesenchyme Cells Affected by disease

Animal Models for Denys-Drash Syndrome or affiliated genes

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MGI Mouse Phenotypes related to Denys-Drash Syndrome:

38
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053808.5MECOM, NR5A1, PAX2, PDGFA, WT1
2MP:00053678.4CD2AP, NPHS1, PAX2, PDGFA, WT1
3MP:00053898.3MECOM, NR5A1, PAX2, PDGFA, WT1
4MP:00053857.7CD2AP, MECOM, NR5A1, PAX2, PDGFA, WT1
5MP:00107686.9CD2AP, MECOM, NPHS1, NR5A1, PAX2, PDGFA

Publications for Denys-Drash Syndrome

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Articles related to Denys-Drash Syndrome:

(show top 50)    (show all 80)
idTitleAuthorsYear
1
Refining the Diagnosis of Congenital Nephrotic Syndrome on Long-term Stored Tissue: c.1097G&gt;A (p.(Arg366His)) WT1 Mutation Causing Denys Drash Syndrome. (26882358)
2016
2
Bilateral Wilms' tumors in an infant with Denys-Drash syndrome and rarely seen truncation mutation in the WT1 gene-exon 6. (26628814)
2015
3
Clinical features and an atypical WT1 mutant site in a child with incomplete Denys-Drash syndrome. (24625882)
2014
4
An unusual presentation of denys-drash syndrome due to bigenic disease. (24379226)
2014
5
Denys-Drash syndrome, septated vagina and low level of anti-Mullerian hormone in male neonate. (25077094)
2014
6
A familial WT1 mutation associated with incomplete Denys-Drash syndrome. (23715653)
2013
7
Early presentation of bilateral gonadoblastomas in a Denys-Drash syndrome patient: a cautionary tale for prophylactic gonadectomy. (23729537)
2013
8
A novel WT1 heterozygous nonsense mutation (p.K248X) causing a mild and slightly progressive nephropathy in a 46,XY patient with Denys-Drash syndrome. (21559934)
2011
9
Clinical pictures and novel mutations of WT1-associated Denys-Drash syndrome in two Chinese children. (21851196)
2011
10
A murine model of Denys-Drash syndrome reveals novel transcriptional targets of WT1 in podocytes. (19797313)
2010
11
The novel WT1 gene mutation p.H377N associated to Denys-Drash syndrome. (20562648)
2010
12
Case report: WT1 exon 6 truncation mutation and ambiguous genitalia in a patient with Denys-Drash syndrome. (18197048)
2008
13
Denys-Drash syndrome and congenital diaphragmatic hernia: another case with the 1097G &gt; A(Arg366His) mutation. (18203154)
2008
14
Effects on kidney disease, fertility and development in mice inheriting a protein-truncating Denys-Drash syndrome allele (Wt1tmT396). (18040647)
2008
15
Mixed gonadal dysgenesis and Denys-Drash syndrome: urologists should screen for nephrotic syndrome. (18163932)
2007
16
Impaired glomerular maturation and lack of VEGF165b in Denys-Drash syndrome. (17267748)
2007
17
A novel WT1 missense mutation presenting with Denys-Drash syndrome and cortical atrophy. (16303781)
2006
18
Denys-Drash syndrome (DDS). (16823575)
2006
19
Hydrothorax in a patient with Denys-Drash syndrome associated with a diaphragmatic defect. (16932893)
2006
20
Outcome of renal transplantation for Wilms' tumor and Denys-Drash syndrome: a report of the North American Pediatric Renal Transplant Cooperative Study. (15910385)
2005
21
A WT1 exon 1 mutation in a child diagnosed with Denys-Drash syndrome. (15503171)
2005
22
Denys-Drash syndrome. (15758579)
2005
23
Denys-Drash syndrome. (15026863)
2004
24
A novel mutation of WT1 exon 9 in a patient with Denys-Drash syndrome and pyloric stenosis. (15349765)
2004
25
The dysregulated glomerular cell growth in Denys-Drash syndrome. (15232745)
2004
26
Murine Denys-Drash syndrome: evidence of podocyte de-differentiation and systemic mediation of glomerulosclerosis. (12915483)
2003
27
A necropsy case of Denys-Drash syndrome with a WT1 mutation in exon 7. (12161615)
2002
28
Wilms tumor in a pediatric renal transplant recipient with unexpected Denys-Drash syndrome. (12493420)
2002
29
Novel WT1 mutation (C388Y) in a female child with Denys-Drash syndrome. (11519891)
2001
30
Pulmonary dysplasia, Denys-Drash syndrome and Wilms tumor 1 gene mutation in twins. (11322369)
2001
31
Novel WT1 exon 9 mutation (D396Y) in a patient with early onset Denys Drash syndrome. (10738002)
2000
32
Hemolytic uremic syndrome associated with Denys-Drash syndrome. (11045393)
2000
33
A novel missense mutation of the WT1 gene causing Denys-Drash syndrome with exceptionally mild renal manifestations. (10799199)
2000
34
A zinc finger truncation of murine WT1 results in the characteristic urogenital abnormalities of Denys-Drash syndrome. (10077614)
1999
35
Unexpected Wilms' tumor in a pediatric renal transplant recipient: suspected Denys-Drash syndrome. (10371996)
1999
36
Renal transplantation in the management of bilateral Wilms' tumour (BWT) and of Denys-Drash syndrome (DDS). (9641183)
1998
37
Regulation of renal EGF receptor expression is normal in Denys-Drash syndrome. (9291179)
1997
38
Atypical presentation of Denys-Drash syndrome in a female with a novel Wt1 gene mutation. (9125334)
1996
39
A novel mutation H373Y in the Wilms' tumor suppressor gene, WT1, associated with Denys-Drash syndrome. (8956030)
1996
40
Nephropathy with Wilms tumour or gonadal dysgenesis: incomplete Denys-Drash syndrome or separate diseases? (7556327)
1995
41
Aberrant proteoglycan composition of the glomerular basement membrane in a patient with Denys-Drash syndrome. (8808212)
1995
42
WT1 mutations associated with incomplete Denys-Drash syndrome define a domain predicted to behave in a dominant-negative fashion. (7959750)
1994
43
Further evidence that imbalance of WT1 isoforms may be involved in Denys-Drash syndrome. (8281163)
1993
44
A novel mutation of the WT1 gene (a tumor suppressor gene for Wilms' tumor) in a patient with Denys-Drash syndrome. (8281164)
1993
45
A novel insertional mutation at the third zinc finger coding region of the WT1 gene in Denys-Drash syndrome. (8098976)
1993
46
A point mutation found in the WT1 gene in a sporadic Wilms' tumor without genitourinary abnormalities is identical with the most frequent point mutation in Denys-Drash syndrome. (8381368)
1993
47
Denys-Drash syndrome: relating a clinical disorder to genetic alterations in the tumor suppressor gene WT1. (8229473)
1993
48
Evidence that WT1 mutations in Denys-Drash syndrome patients may act in a dominant-negative fashion. (8388765)
1993
49
Dominant negative mutations in the Wilms tumour (WT1) gene cause Denys-Drash syndrome--proof that a tumour-suppressor gene plays a crucial role in normal genitourinary development. (1338905)
1992
50
Inherited WT1 mutation in Denys-Drash syndrome. (1327525)
1992

Variations for Denys-Drash Syndrome

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UniProtKB/Swiss-Prot genetic disease variations for Denys-Drash Syndrome:

67 (show all 24)
id Symbol AA change Variation ID SNP ID
1WT1p.Cys330TyrVAR_007743
2WT1p.Cys360GlyVAR_007744
3WT1p.Arg366CysVAR_007745
4WT1p.Arg366HisVAR_007746
5WT1p.His373GlnVAR_007747
6WT1p.Arg394TrpVAR_007750
7WT1p.Asp396AsnVAR_007751
8WT1p.Asp396GlyVAR_007752
9WT1p.Met342ArgVAR_015054
10WT1p.Cys355TyrVAR_015055
11WT1p.His373TyrVAR_015056
12WT1p.His377ArgVAR_015057
13WT1p.Cys385ArgVAR_015058
14WT1p.Cys388PheVAR_015059
15WT1p.Arg394GlnVAR_015061
16WT1p.Leu398ProVAR_015062
17WT1p.Cys360TyrVAR_043800
18WT1p.Arg366LeuVAR_043802
19WT1p.Gln369ProVAR_043803
20WT1p.Cys388TyrVAR_043806
21WT1p.Arg394ProVAR_043808
22WT1p.Asp396TyrVAR_043809
23WT1p.His401TyrVAR_043811
24WT1p.His405ArgVAR_043812

Clinvar genetic disease variations for Denys-Drash Syndrome:

5 (show all 11)
id Gene Variation Type Significance SNP ID Assembly Location
1WT1NM_024426.4(WT1): c.1384C> T (p.Arg462Trp)single nucleotide variantPathogenicrs121907900GRCh37Chr 11, 32413566: 32413566
2WT1NM_024426.4(WT1): c.1301G> A (p.Arg434His)single nucleotide variantPathogenicrs121907901GRCh37Chr 11, 32414250: 32414250
3WT1NM_024426.4(WT1): c.1391A> G (p.Asp464Gly)single nucleotide variantPathogenicrs121907902GRCh37Chr 11, 32413559: 32413559
4WT1NM_024426.4(WT1): c.1390G> A (p.Asp464Asn)single nucleotide variantPathogenicrs28941778GRCh37Chr 11, 32413560: 32413560
5WT1NM_024426.4(WT1): c.1385G> C (p.Arg462Pro)single nucleotide variantPathogenicrs121907903GRCh37Chr 11, 32413565: 32413565
6WT1NM_024426.4(WT1): c.1193G> A (p.Cys398Tyr)single nucleotide variantPathogenicrs121907904GRCh37Chr 11, 32417859: 32417859
7WT1NM_024426.4(WT1): c.1432+5G> Asingle nucleotide variantPathogenicrs587776576GRCh38Chr 11, 32391967: 32391967
8WT1NM_024426.4(WT1): c.1333C> T (p.His445Tyr)single nucleotide variantPathogenicrs28942089GRCh37Chr 11, 32414218: 32414218
9WT1NM_024426.4(WT1): c.1282T> G (p.Cys428Gly)single nucleotide variantPathogenicrs121907905GRCh37Chr 11, 32414269: 32414269
10WT1NM_024426.4(WT1): c.1288C> T (p.Arg430Ter)single nucleotide variantPathogenicrs121907906GRCh37Chr 11, 32414263: 32414263
11WT1NM_024426.4(WT1): c.1323C> G (p.His441Gln)single nucleotide variantPathogenicrs121907907GRCh37Chr 11, 32414228: 32414228

Expression for genes affiliated with Denys-Drash Syndrome

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Search GEO for disease gene expression data for Denys-Drash Syndrome.

Pathways for genes affiliated with Denys-Drash Syndrome

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Pathways related to Denys-Drash Syndrome according to GeneCards Suite gene sharing:

idSuper pathwaysScoreTop Affiliating Genes
19.6PAX2, PDGFA
29.5CD2AP, NPHS1
39.5CD2AP, NPHS1

GO Terms for genes affiliated with Denys-Drash Syndrome

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Biological processes related to Denys-Drash Syndrome according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1metanephric mesenchyme developmentGO:007207510.1PAX2, WT1
2metanephric epithelium developmentGO:007220710.1PAX2, WT1
3camera-type eye developmentGO:004301010.1PAX2, WT1
4sex determinationGO:00075309.7SRY, WT1
5cell differentiationGO:00301548.7MECOM, NR5A1, SRY
6positive regulation of transcription, DNA-templatedGO:00458938.2MECOM, NR5A1, SRY, WT1

Molecular functions related to Denys-Drash Syndrome according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1protein bindingGO:00055158.1CD2AP, NR5A1, PAX2, SRY, WT1

Sources for Denys-Drash Syndrome

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2CDC
14ExPASy
15FDA
16FMA
24GTR
25HGMD
26HMDB
27ICD10
28ICD10 via Orphanet
29ICD9CM
30IUPHAR
31KEGG
34MedGen
36MeSH
37MESH via Orphanet
38MGI
41NCI
42NCIt
43NDF-RT
46NINDS
47Novoseek
49OMIM
50OMIM via Orphanet
54PubMed
55QIAGEN
60SNOMED-CT via Orphanet
64Tumor Gene Family of Databases
65UMLS
66UMLS via Orphanet