MCID: DNY001
MIFTS: 53

Denys-Drash Syndrome malady

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

Aliases & Classifications for Denys-Drash Syndrome

About this section
Sources:
11Disease Ontology, 12diseasecard, 13DISEASES, 24GeneTests, 25Genetics Home Reference, 26GTR, 30ICD10 via Orphanet, 34LifeMap Discovery®, 36MedGen, 38MeSH, 39MESH via Orphanet, 44NCIt, 47NIH Rare Diseases, 49Novoseek, 51OMIM, 53Orphanet, 61SNOMED-CT, 63The Human Phenotype Ontology, 67UMLS, 68UMLS via Orphanet, 69UniProtKB/Swiss-Prot
See all MalaCards sources

Aliases & Descriptions for Denys-Drash Syndrome:

Name: Denys-Drash Syndrome 51 34 11 47 24 25 53 69 12 49 38 13 67
Drash Syndrome 47 24 25 53 26
Wilms Tumor and Pseudohermaphroditism 47 24 25 53
Nephropathy, Wilms Tumor, and Genital Anomalies 47 25
 
Dds 25 69
Nephropathy Associated with Male Pseudohermaphroditism and Wilms' Tumor 47
Pseudohermaphroditism, Nephron Disorder and Wilms' Tumor 47

Characteristics:

Orphanet epidemiological data:

53
denys-drash syndrome:
Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal

HPO:

63
denys-drash syndrome:
Inheritance: autosomal dominant inheritance, somatic mutation

Classifications:



External Ids:

OMIM51 194080
Disease Ontology11 DOID:3764
MeSH38 D030321
NCIt44 C84668
Orphanet53 ORPHA220
SNOMED-CT61 236385009
MESH via Orphanet39 D030321
UMLS via Orphanet68 C0950121
ICD10 via Orphanet30 N04.1
MedGen36 C0950121

Summaries for Denys-Drash Syndrome

About this section
NIH Rare Diseases:47 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 mixed gonadal dysgenesis and frasier syndrome, and has symptoms including male pseudohermaphroditism, proteinuria and nephrotic syndrome. An important gene associated with Denys-Drash Syndrome is WT1 (Wilms Tumor 1), and among its related pathways are Nephrin interactions and Neural Stem Cell Differentiation Pathways and Lineage-specific Markers. Affiliated tissues include kidney and testes, and related mouse phenotypes are endocrine/exocrine gland and cardiovascular system.

Disease Ontology:11 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).

Genetics Home Reference:25 Denys-Drash syndrome is a condition that affects the kidneys and genitalia.

UniProtKB/Swiss-Prot:69 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.

Wikipedia:70 Denys–Drash syndrome (DDS) or Drash syndrome is a rare disorder or syndrome characterized by gonadal... more...

Description from OMIM:51 194080

Related Diseases for Denys-Drash Syndrome

About this section

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

(show top 50)    (show all 68)
idRelated DiseaseScoreTop Affiliating Genes
1mixed gonadal dysgenesis29.8NR5A1, WT1
2frasier syndrome11.2
3dentin dysplasia, type ii10.9
4diastrophic dysplasia10.9
5dentin dysplasia, type i, with microdontia and misshapen teeth10.9
6mohr-tranebjaerg syndrome10.9
7dissociative disorder10.8
8darier disease10.7
9dentin dysplasia10.7
10liver sarcoma10.3PAX2, WT1
11pfeiffer syndrome type 310.3NPHS1, WT1
12keratosis follicularis, dwarfism, and cerebral atrophy10.3PAX2, WT1
13sclerosing hemangioma10.3PAX2, WT1
14gonadal dysgenesis10.3
15pfeiffer syndrome type 210.2NPHS1, NPHS2
16mucinous adenofibroma10.2PAX2, WT1
17stomatitis10.2NPHS1, NPHS2
18testicular gonadoblastoma10.2NR5A1, WT1
19spastic monoplegia10.2NPHS1, NPHS2
20acute myeloid leukemia with cebpa somatic mutations10.2CD2AP, NPHS1
21gonadoblastoma10.2
22glomerulosclerosis10.2
23diffuse mesangial sclerosis10.2
24familial idiopathic steroid-resistant nephrotic syndrome with diffuse mesangial proliferation10.2CD2AP, NPHS2
25hypopigmentation of eyelid10.1NPHS1, NPHS2
26pseudohermaphroditism10.0
27klinefelter's syndrome10.0NR5A1, WT1
28lymphoma10.0
29hemolytic-uremic syndrome10.0
30pyloric stenosis10.0
31congenital diaphragmatic hernia10.0
32septate vagina10.0
33coronary artery disease10.0
34artery disease10.0
35corneal dystrophy, fuchs endothelial, 810.0NPHS1, NPHS2
36tooth disease10.0NR5A1, WT1
37exocrine pancreatic insufficiency9.9NPHS1, NPHS2, WT1
38endotheliitis9.9
39coronary thrombosis9.9NPHS1, NPHS2, WT1
40unna-thost palmoplantar keratoderma9.9PAX2, PDGFA, WT1
41myocardial infarction9.8
42muscular dystrophy-dystroglycanopathy , type a, 19.8CD2AP, NPHS2, PAX2
43nasopharyngeal carcinoma 29.8CD2AP, NPHS1, NPHS2
44gastrointestinal system cancer9.8BAX, WT1
45leprosy9.8
46obesity9.7
47acute myocardial infarction9.7
48end stage renal failure9.7
49gastric cancer9.7
50lepromatous leprosy9.7

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



Diseases related to denys-drash syndrome

Symptoms for Denys-Drash Syndrome

About this section

Symptoms by clinical synopsis from OMIM:

194080

Clinical features from OMIM:

194080

Human phenotypes related to Denys-Drash Syndrome:

 63 (show all 16)
id Description HPO Frequency HPO Source Accession
1 male pseudohermaphroditism63 hallmark (90%) HP:0000037
2 proteinuria63 hallmark (90%) HP:0000093
3 nephrotic syndrome63 hallmark (90%) HP:0000100
4 nephropathy63 hallmark (90%) HP:0000112
5 nephroblastoma63 hallmark (90%) HP:0002667
6 hypertension63 typical (50%) HP:0000822
7 gonadal dysgenesis63 occasional (7.5%) HP:0000133
8 ambiguous genitalia, male63 HP:0000033
9 ambiguous genitalia, female63 HP:0000061
10 focal segmental glomerulosclerosis63 HP:0000097
11 ovarian gonadoblastoma63 HP:0000149
12 congenital diaphragmatic hernia63 HP:0000776
13 diffuse mesangial sclerosis63 HP:0001967
14 gonadal tissue inappropriate for external genitalia or chromosomal sex63 HP:0003248
15 stage 5 chronic kidney disease63 HP:0003774
16 true hermaphroditism63 HP:0010459

Drugs & Therapeutics for Denys-Drash Syndrome

About this section

Interventional clinical trials:

idNameStatusNCT IDPhase
1Registry for Patients With Wilms' Tumor Suppressor Gene 1 (WT1) Mutation Associated DiseasesCompletedNCT01252901
2Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at SanfordRecruitingNCT01793168

Search NIH Clinical Center for Denys-Drash Syndrome


Cochrane evidence based reviews: denys-drash syndrome

Genetic Tests for Denys-Drash Syndrome

About this section

Genetic tests related to Denys-Drash Syndrome:

id Genetic test Affiliating Genes
1 Drash Syndrome26
2 Denys-Drash Syndrome24 WT1

Anatomical Context for Denys-Drash Syndrome

About this section

MalaCards organs/tissues related to Denys-Drash Syndrome:

35
Kidney, Testes

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

About this section

MGI Mouse Phenotypes related to Denys-Drash Syndrome:

40
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053798.9BAX, CD2AP, NR5A1, PAX2, WT1
2MP:00053858.2CD2AP, NPHS2, NR5A1, PAX2, PDGFA, WT1
3MP:00053897.8BAX, NR5A1, PAX2, PDGFA, WT1
4MP:00053677.8BAX, CD2AP, NPHS1, NPHS2, PAX2, PDGFA
5MP:00053767.6BAX, CD2AP, NPHS1, NPHS2, NR5A1, PDGFA
6MP:00107687.2BAX, CD2AP, NPHS1, NPHS2, NR5A1, PAX2

Publications for Denys-Drash Syndrome

About this section

Articles related to Denys-Drash Syndrome:

(show top 50)    (show all 82)
idTitleAuthorsYear
1
WT1 Haploinsufficiency Supports Milder Renal Manifestation in Two Patients with Denys-Drash Syndrome. (28081536)
2017
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 novel WT1 gene mutation in a newborn infant diagnosed with Denys-Drash syndrome. (22876585)
2012
7
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
8
Clinical pictures and novel mutations of WT1-associated Denys-Drash syndrome in two Chinese children. (21851196)
2011
9
Denys-Drash syndrome and gonadoblastoma in a patient with Klinefelter syndrome. (21552011)
2011
10
Denys-Drash syndrome with neonatal renal failure in monozygotic twins due to c.1097G>A mutation in the WT1 gene. (21434831)
2011
11
A murine model of Denys-Drash syndrome reveals novel transcriptional targets of WT1 in podocytes. (19797313)
2010
12
The novel WT1 gene mutation p.H377N associated to Denys-Drash syndrome. (20562648)
2010
13
Case report: WT1 exon 6 truncation mutation and ambiguous genitalia in a patient with Denys-Drash syndrome. (18197048)
2008
14
Mixed gonadal dysgenesis and Denys-Drash syndrome: urologists should screen for nephrotic syndrome. (18163932)
2007
15
Case report: Denys- Drash syndrome. (18076855)
2007
16
A proteomic investigation of glomerular podocytes from a Denys-Drash syndrome patient with a mutation in the Wilms tumour suppressor gene WT1. (17295355)
2007
17
Denys-Drash syndrome (DDS). (16823575)
2006
18
Hydrothorax in a patient with Denys-Drash syndrome associated with a diaphragmatic defect. (16932893)
2006
19
A novel WT1 missense mutation presenting with Denys-Drash syndrome and cortical atrophy. (16303781)
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
Denys-Drash syndrome. (15758579)
2005
22
Denys-Drash syndrome. (15026863)
2004
23
A necropsy case of Denys-Drash syndrome with a WT1 mutation in exon 7. (12161615)
2002
24
Wilms tumor in a pediatric renal transplant recipient with unexpected Denys-Drash syndrome. (12493420)
2002
25
Novel WT1 mutation (C388Y) in a female child with Denys-Drash syndrome. (11519891)
2001
26
Novel WT1 exon 9 mutation (D396Y) in a patient with early onset Denys Drash syndrome. (10738002)
2000
27
Hemolytic uremic syndrome associated with Denys-Drash syndrome. (11045393)
2000
28
A novel missense mutation of the WT1 gene causing Denys-Drash syndrome with exceptionally mild renal manifestations. (10799199)
2000
29
Genetic analysis of two female patients with incomplete Denys-Drash syndrome. (11228042)
2000
30
WT1 and PAX-2 podocyte expression in Denys-Drash syndrome and isolated diffuse mesangial sclerosis. (9916932)
1999
31
Transcriptional regulation of PDGF-A and TGF-beta by +KTS WT1 deletion mutants and a mutant mimicking Denys-Drash syndrome. (10586431)
1999
32
A zinc finger truncation of murine WT1 results in the characteristic urogenital abnormalities of Denys-Drash syndrome. (10077614)
1999
33
In utero nephropathy, Denys-Drash syndrome and Potter phenotype. (9745866)
1998
34
Regulation of renal EGF receptor expression is normal in Denys-Drash syndrome. (9291179)
1997
35
Atypical presentation of Denys-Drash syndrome in a female with a novel Wt1 gene mutation. (9125334)
1996
36
A newly identified exonic mutation of the WT1 gene in a patient with Denys-Drash syndrome. (8741319)
1996
37
Diaphragmatic hernia in Denys-Drash syndrome. (7645607)
1995
38
Denys-Drash syndrome. (8772891)
1995
39
DNA binding capacity of the WT1 protein is abolished by Denys-Drash syndrome WT1 point mutations. (7795587)
1995
40
Nephropathy with Wilms tumour or gonadal dysgenesis: incomplete Denys-Drash syndrome or separate diseases? (7556327)
1995
41
WT1 mutations associated with incomplete Denys-Drash syndrome define a domain predicted to behave in a dominant-negative fashion. (7959750)
1994
42
Further evidence that imbalance of WT1 isoforms may be involved in Denys-Drash syndrome. (8281163)
1993
43
A novel mutation of the WT1 gene (a tumor suppressor gene for Wilms' tumor) in a patient with Denys-Drash syndrome. (8281164)
1993
44
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
45
Denys-Drash syndrome: relating a clinical disorder to genetic alterations in the tumor suppressor gene WT1. (8229473)
1993
46
A novel zinc finger mutation in a patient with Denys-Drash syndrome. (8111391)
1993
47
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
48
Inherited WT1 mutation in Denys-Drash syndrome. (1327525)
1992
49
Constitutional mutations in the WT1 gene in patients with Denys-Drash syndrome. (1338906)
1992
50
Germline mutations in the Wilms' tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. (1655284)
1991

Variations for Denys-Drash Syndrome

About this section

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

69 (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)SNVPathogenicrs121907900GRCh37Chr 11, 32413566: 32413566
2WT1NM_024426.4(WT1): c.1301G> A (p.Arg434His)SNVPathogenicrs121907901GRCh37Chr 11, 32414250: 32414250
3WT1NM_024426.4(WT1): c.1391A> G (p.Asp464Gly)SNVPathogenicrs121907902GRCh37Chr 11, 32413559: 32413559
4WT1NM_024426.4(WT1): c.1390G> A (p.Asp464Asn)SNVPathogenicrs28941778GRCh37Chr 11, 32413560: 32413560
5WT1NM_024426.4(WT1): c.1385G> C (p.Arg462Pro)SNVPathogenicrs121907903GRCh37Chr 11, 32413565: 32413565
6WT1NM_024426.4(WT1): c.1193G> A (p.Cys398Tyr)SNVPathogenicrs121907904GRCh37Chr 11, 32417859: 32417859
7WT1NM_024426.4(WT1): c.1432+5G> ASNVPathogenicrs587776576GRCh38Chr 11, 32391967: 32391967
8WT1NM_024426.4(WT1): c.1333C> T (p.His445Tyr)SNVPathogenicrs28942089GRCh37Chr 11, 32414218: 32414218
9WT1NM_024426.4(WT1): c.1282T> G (p.Cys428Gly)SNVPathogenicrs121907905GRCh37Chr 11, 32414269: 32414269
10WT1NM_024426.4(WT1): c.1288C> T (p.Arg430Ter)SNVPathogenicrs121907906GRCh37Chr 11, 32414263: 32414263
11WT1NM_024426.4(WT1): c.1323C> G (p.His441Gln)SNVPathogenicrs121907907GRCh37Chr 11, 32414228: 32414228

Copy number variations for Denys-Drash Syndrome from CNVD:

6
id CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
153562113100000036400000Copy numberWT1Denys-drash syndrome
253587113100000036400000Copy numberWT1Denys-drash syndrome

Expression for genes affiliated with Denys-Drash Syndrome

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

Pathways for genes affiliated with Denys-Drash Syndrome

About this section

GO Terms for genes affiliated with Denys-Drash Syndrome

About this section

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

idNameGO IDScoreTop Affiliating Genes
1slit diaphragmGO:00360579.6NPHS1, NPHS2

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

(show all 14)
idNameGO IDScoreTop Affiliating Genes
1metanephric epithelium developmentGO:007220710.3PAX2, WT1
2metanephric mesenchyme developmentGO:007207510.2PAX2, WT1
3mesenchymal to epithelial transitionGO:006023110.2PAX2, WT1
4glomerular basement membrane developmentGO:003283610.1NPHS1, WT1
5negative regulation of female gonad developmentGO:200019510.0NR5A1, WT1
6excretionGO:000758810.0NPHS1, NPHS2
7camera-type eye developmentGO:004301010.0PAX2, WT1
8branching involved in ureteric bud morphogenesisGO:00016589.9PAX2, WT1
9germ cell developmentGO:00072819.6BAX, WT1
10adrenal gland developmentGO:00303259.6NR5A1, WT1
11positive regulation of male gonad developmentGO:20000209.4NR5A1, WT1
12response to woundingGO:00096119.4BAX, PDGFA
13tissue developmentGO:00098889.2NR5A1, WT1
14male gonad developmentGO:00085849.0BAX, NR5A1, WT1

Sources for Denys-Drash Syndrome

About this section
2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
26GTR
27HGMD
28HMDB
29ICD10
30ICD10 via Orphanet
31ICD9CM
32IUPHAR
33KEGG
36MedGen
38MeSH
39MESH via Orphanet
40MGI
43NCI
44NCIt
45NDF-RT
48NINDS
49Novoseek
51OMIM
52OMIM via Orphanet
56PubMed
57QIAGEN
62SNOMED-CT via Orphanet
66Tumor Gene Family of Databases
67UMLS
68UMLS via Orphanet