DDS
MCID: DNY001
MIFTS: 52

Denys-Drash Syndrome (DDS) malady

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

Aliases & Classifications for Denys-Drash Syndrome

Aliases & Descriptions for Denys-Drash Syndrome:

Name: Denys-Drash Syndrome 54 38 12 50 24 25 56 66 13 52 42 14 69
Drash Syndrome 50 24 25 56 29
Wilms Tumor and Pseudohermaphroditism 50 24 25 56
Nephropathy, Wilms Tumor, and Genital Anomalies 50 25
Dds 25 66
Nephropathy Associated with Male Pseudohermaphroditism and Wilms' Tumor 50
Pseudohermaphroditism, Nephron Disorder and Wilms' Tumor 50

Characteristics:

Orphanet epidemiological data:

56
denys-drash syndrome
Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

HPO:

32
denys-drash syndrome:
Inheritance autosomal dominant inheritance somatic mutation


Classifications:



External Ids:

OMIM 54 194080
Disease Ontology 12 DOID:3764
MeSH 42 D030321
NCIt 47 C84668
SNOMED-CT 64 236385009
Orphanet 56 ORPHA220
MESH via Orphanet 43 D030321
UMLS via Orphanet 70 C0950121
ICD10 via Orphanet 34 N04.1
MedGen 40 C0950121
UMLS 69 C0950121

Summaries for Denys-Drash Syndrome

NIH Rare Diseases : 50 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 frasier syndrome and gastric cancer, and has symptoms including hypertension, nephropathy and nephrotic syndrome. An important gene associated with Denys-Drash Syndrome is WT1 (Wilms Tumor 1), and among its related pathways/superpathways are Neural Stem Cell Differentiation Pathways and Lineage-specific Markers and Ceramide signaling pathway. Affiliated tissues include Kidney, kidney and testes, and related phenotypes are cardiovascular system and homeostasis/metabolism

Disease Ontology : 12 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 : 66 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 : 71 Denys–Drash syndrome (DDS) or Drash syndrome is a rare disorder or syndrome characterized by gonadal... more...

Description from OMIM: 194080

Related Diseases for Denys-Drash Syndrome

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

(show top 50) (show all 73)
id Related Disease Score Top Affiliating Genes
1 frasier syndrome 30.2 BAX CD2AP NPHS1 NPHS2 NR5A1 PAX2
2 gastric cancer 29.1 CD2AP NPHS1 NPHS2 PAX2 WT1
3 mohr-tranebjaerg syndrome 10.9
4 dentin dysplasia, type ii 10.9
5 diastrophic dysplasia 10.9
6 dentin dysplasia, type i, with microdontia and misshapen teeth 10.9
7 dissociative disorder 10.8
8 darier disease 10.7
9 dentin dysplasia 10.7
10 nephrotic syndrome 10.2
11 gonadal dysgenesis 10.2
12 mucinous adenofibroma 10.2 PAX2 WT1
13 transient pseudohypoaldosteronism 10.2 NPHS1 WT1
14 anterior chamber cleavage disorder, cerebellar hypoplasia, hypothyroidism, and tracheal stenosis 10.2 PAX2 WT1
15 gonadoblastoma 10.2
16 diffuse mesangial sclerosis 10.2
17 meninges hemangiopericytoma 10.2 PAX2 WT1
18 pauci-immune glomerulonephritis 10.1 NPHS1 NPHS2
19 glaucoma 1, open angle, e 10.1 NPHS1 NPHS2
20 aphthous stomatitis 10.1 NPHS1 NPHS2
21 gestational trophoblastic neoplasm 10.1 NR5A1 WT1
22 renal agenesis, unilateral 10.1 CD2AP NPHS2
23 nodular tenosynovitis 10.1 PAX2 WT1
24 cone dystrophy 10.1 NR5A1 WT1
25 hypertrichosis of eyelid 10.1 NPHS1 NPHS2
26 sex differentiation disease 10.0 NR5A1 WT1
27 pseudohermaphroditism 10.0
28 mixed germ cell-sex cord neoplasm 10.0 NPHS1 NPHS2
29 familial nephrotic syndrome 10.0 NPHS1 NPHS2 WT1
30 hemolytic-uremic syndrome 10.0
31 pyloric stenosis 10.0
32 mixed gonadal dysgenesis 10.0
33 congenital diaphragmatic hernia 10.0
34 lymphoma 10.0
35 kidney disease 10.0
36 septate vagina 10.0
37 hypothyroidism, congenital, nongoitrous, 3 10.0 NPHS1 NPHS2
38 muscular dystrophy-dystroglycanopathy , type b, 1 10.0 CD2AP NPHS2 PAX2
39 coronary artery disease 10.0
40 artery disease 10.0
41 sick sinus syndrome 3 10.0 CD2AP NPHS1 NPHS2
42 hemiplegia 10.0 CD2AP NPHS1 NPHS2
43 biliary cirrhosis, primary, 2 9.9 CD2AP NPHS1 NPHS2
44 endotheliitis 9.9
45 46 xx gonadal dysgenesis 9.9 NR5A1 WT1
46 myocardial infarction 9.8
47 congenital torticollis 9.8 CD2AP NPHS1 NPHS2 WT1
48 focal segmental glomerulosclerosis 9.8 CD2AP NPHS1 NPHS2 WT1
49 malignant hyperthermia susceptibility 1 9.8 CD2AP NPHS1 NPHS2 WT1
50 transient refractive change 9.8 CD2AP NPHS1 NPHS2 WT1

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



Diseases related to Denys-Drash Syndrome

Symptoms & Phenotypes for Denys-Drash Syndrome

Symptoms by clinical synopsis from OMIM:

194080

Clinical features from OMIM:

194080

Human phenotypes related to Denys-Drash Syndrome:

32 (show all 15)
id Description HPO Frequency HPO Source Accession
1 hypertension 32 HP:0000822
2 nephropathy 32 HP:0000112
3 nephrotic syndrome 32 HP:0000100
4 male pseudohermaphroditism 32 HP:0000037
5 true hermaphroditism 32 HP:0010459
6 congenital diaphragmatic hernia 32 HP:0000776
7 nephroblastoma 32 HP:0002667
8 ambiguous genitalia, male 32 HP:0000033
9 gonadal dysgenesis 32 HP:0000133
10 stage 5 chronic kidney disease 32 HP:0003774
11 ambiguous genitalia, female 32 HP:0000061
12 ovarian gonadoblastoma 32 HP:0000149
13 gonadal tissue inappropriate for external genitalia or chromosomal sex 32 HP:0003248
14 focal segmental glomerulosclerosis 32 HP:0000097
15 diffuse mesangial sclerosis 32 HP:0001967

MGI Mouse Phenotypes related to Denys-Drash Syndrome:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.85 CD2AP NPHS2 NR5A1 PAX2 PDGFA WT1
2 homeostasis/metabolism MP:0005376 9.8 BAX CD2AP NPHS1 NPHS2 NR5A1 PDGFA
3 mortality/aging MP:0010768 9.76 BAX CD2AP NPHS1 NPHS2 NR5A1 PAX2
4 endocrine/exocrine gland MP:0005379 9.72 NR5A1 PAX2 WT1 BAX CD2AP
5 renal/urinary system MP:0005367 9.5 BAX CD2AP NPHS1 NPHS2 PAX2 PDGFA
6 reproductive system MP:0005389 9.02 BAX NR5A1 PAX2 PDGFA WT1

Drugs & Therapeutics for Denys-Drash Syndrome

Interventional clinical trials:


id Name Status NCT ID Phase
1 Registry for Patients With Wilms' Tumor Suppressor Gene 1 (WT1) Mutation Associated Diseases Completed NCT01252901
2 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168

Search NIH Clinical Center for Denys-Drash Syndrome

Cochrane evidence based reviews: denys-drash syndrome

Genetic Tests for Denys-Drash Syndrome

Genetic tests related to Denys-Drash Syndrome:

id Genetic test Affiliating Genes
1 Drash Syndrome 29
2 Denys-Drash Syndrome 24 WT1

Anatomical Context for Denys-Drash Syndrome

MalaCards organs/tissues related to Denys-Drash Syndrome:

39
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 Tissue Anatomical CompartmentCell Relevance
1 Kidney Metanephric Mesenchyme Metanephric Mesenchyme Cells Affected by disease

Publications for Denys-Drash Syndrome

Articles related to Denys-Drash Syndrome:

(show top 50) (show all 82)
id Title Authors Year
1
WT1 Haploinsufficiency Supports Milder Renal Manifestation in Two Patients with Denys-Drash Syndrome. ( 28081536 )
2017
2
Denys-Drash syndrome associated WT1 glutamine 369 mutants have altered sequence-preferences and altered responses to epigenetic modifications. ( 27596598 )
2016
3
Refining the Diagnosis of Congenital Nephrotic Syndrome on Long-term Stored Tissue: c.1097G>A (p.(Arg366His)) WT1 Mutation Causing Denys Drash Syndrome. ( 26882358 )
2016
4
Bilateral Wilms' tumors in an infant with Denys-Drash syndrome and rarely seen truncation mutation in the WT1 gene-exon 6. ( 26628814 )
2015
5
An unusual presentation of denys-drash syndrome due to bigenic disease. ( 24379226 )
2014
6
Clinical features and an atypical WT1 mutant site in a child with incomplete Denys-Drash syndrome. ( 24625882 )
2014
7
Denys-Drash syndrome, septated vagina and low level of anti-Mullerian hormone in male neonate. ( 25077094 )
2014
8
A familial WT1 mutation associated with incomplete Denys-Drash syndrome. ( 23715653 )
2013
9
Early presentation of bilateral gonadoblastomas in a Denys-Drash syndrome patient: a cautionary tale for prophylactic gonadectomy. ( 23729537 )
2013
10
A novel WT1 gene mutation in a newborn infant diagnosed with Denys-Drash syndrome. ( 22876585 )
2012
11
Denys-Drash syndrome with neonatal renal failure in monozygotic twins due to c.1097G>A mutation in the WT1 gene. ( 21434831 )
2011
12
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
13
Denys-Drash syndrome and gonadoblastoma in a patient with Klinefelter syndrome. ( 21552011 )
2011
14
Clinical pictures and novel mutations of WT1-associated Denys-Drash syndrome in two Chinese children. ( 21851196 )
2011
15
A murine model of Denys-Drash syndrome reveals novel transcriptional targets of WT1 in podocytes. ( 19797313 )
2010
16
The novel WT1 gene mutation p.H377N associated to Denys-Drash syndrome. ( 20562648 )
2010
17
Case report: WT1 exon 6 truncation mutation and ambiguous genitalia in a patient with Denys-Drash syndrome. ( 18197048 )
2008
18
Denys-Drash syndrome and congenital diaphragmatic hernia: another case with the 1097G > A(Arg366His) mutation. ( 18203154 )
2008
19
Effects on kidney disease, fertility and development in mice inheriting a protein-truncating Denys-Drash syndrome allele (Wt1tmT396). ( 18040647 )
2008
20
Mixed gonadal dysgenesis and Denys-Drash syndrome: urologists should screen for nephrotic syndrome. ( 18163932 )
2007
21
Impaired glomerular maturation and lack of VEGF165b in Denys-Drash syndrome. ( 17267748 )
2007
22
A proteomic investigation of glomerular podocytes from a Denys-Drash syndrome patient with a mutation in the Wilms tumour suppressor gene WT1. ( 17295355 )
2007
23
Case report: Denys- Drash syndrome. ( 18076855 )
2007
24
Denys-Drash syndrome (DDS). ( 16823575 )
2006
25
Hydrothorax in a patient with Denys-Drash syndrome associated with a diaphragmatic defect. ( 16932893 )
2006
26
A novel WT1 missense mutation presenting with Denys-Drash syndrome and cortical atrophy. ( 16303781 )
2006
27
Outcome of renal transplantation for Wilms' tumor and Denys-Drash syndrome: a report of the North American Pediatric Renal Transplant Cooperative Study. ( 15910385 )
2005
28
Gonadal effects of a mouse Denys-Drash syndrome mutation. ( 16245160 )
2005
29
Clinical course of congenital nephrotic syndrome and Denys-Drash syndrome in Japan. ( 16354210 )
2005
30
[Denys-Drash syndrome. Experience gathered in Erlangen illustrated by two case reports]. ( 16003530 )
2005
31
Denys-Drash syndrome. ( 15758579 )
2005
32
A WT1 exon 1 mutation in a child diagnosed with Denys-Drash syndrome. ( 15503171 )
2005
33
The Wt1+/R394W mouse displays glomerulosclerosis and early-onset renal failure characteristic of human Denys-Drash syndrome. ( 15509792 )
2004
34
A novel mutation of WT1 exon 9 in a patient with Denys-Drash syndrome and pyloric stenosis. ( 15349765 )
2004
35
Denys-Drash syndrome. ( 15026863 )
2004
36
The dysregulated glomerular cell growth in Denys-Drash syndrome. ( 15232745 )
2004
37
Murine Denys-Drash syndrome: evidence of podocyte de-differentiation and systemic mediation of glomerulosclerosis. ( 12915483 )
2003
38
Wilms tumor in a pediatric renal transplant recipient with unexpected Denys-Drash syndrome. ( 12493420 )
2002
39
A necropsy case of Denys-Drash syndrome with a WT1 mutation in exon 7. ( 12161615 )
2002
40
A review of the phenotypic variation due to the Denys-Drash syndrome-associated germline WT1 mutation R362X. ( 11933209 )
2002
41
A mutant form of the Wilms' tumor suppressor gene WT1 observed in Denys-Drash syndrome interferes with glomerular capillary development. ( 12138137 )
2002
42
Novel WT1 mutation (C388Y) in a female child with Denys-Drash syndrome. ( 11519891 )
2001
43
Association of partial gonadal dysgenesis, nephropathy and WT1 gene mutation without Wilms' tumor: incomplete Denys-Drash syndrome. ( 11393579 )
2001
44
Pulmonary dysplasia, Denys-Drash syndrome and Wilms tumor 1 gene mutation in twins. ( 11322369 )
2001
45
Genetic analysis of two female patients with incomplete Denys-Drash syndrome. ( 11228042 )
2000
46
Hemolytic uremic syndrome associated with Denys-Drash syndrome. ( 11045393 )
2000
47
A novel missense mutation of the WT1 gene causing Denys-Drash syndrome with exceptionally mild renal manifestations. ( 10799199 )
2000
48
Absence of correlation between genotype and the severity of diffuse mesangial sclerosis in Denys-Drash syndrome. ( 10805477 )
2000
49
Novel WT1 exon 9 mutation (D396Y) in a patient with early onset Denys Drash syndrome. ( 10738002 )
2000
50
Transcriptional regulation of PDGF-A and TGF-beta by +KTS WT1 deletion mutants and a mutant mimicking Denys-Drash syndrome. ( 10586431 )
1999

Variations for Denys-Drash Syndrome

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

66 (show all 24)
id Symbol AA change Variation ID SNP ID
1 WT1 p.Cys330Tyr VAR_007743
2 WT1 p.Cys360Gly VAR_007744
3 WT1 p.Arg366Cys VAR_007745
4 WT1 p.Arg366His VAR_007746
5 WT1 p.His373Gln VAR_007747
6 WT1 p.Arg394Trp VAR_007750
7 WT1 p.Asp396Asn VAR_007751
8 WT1 p.Asp396Gly VAR_007752
9 WT1 p.Met342Arg VAR_015054
10 WT1 p.Cys355Tyr VAR_015055
11 WT1 p.His373Tyr VAR_015056
12 WT1 p.His377Arg VAR_015057
13 WT1 p.Cys385Arg VAR_015058
14 WT1 p.Cys388Phe VAR_015059
15 WT1 p.Arg394Gln VAR_015061
16 WT1 p.Leu398Pro VAR_015062
17 WT1 p.Cys360Tyr VAR_043800
18 WT1 p.Arg366Leu VAR_043802
19 WT1 p.Gln369Pro VAR_043803
20 WT1 p.Cys388Tyr VAR_043806
21 WT1 p.Arg394Pro VAR_043808
22 WT1 p.Asp396Tyr VAR_043809
23 WT1 p.His401Tyr VAR_043811
24 WT1 p.His405Arg VAR_043812

ClinVar genetic disease variations for Denys-Drash Syndrome:

6 (show all 13)
id Gene Variation Type Significance SNP ID Assembly Location
1 WT1 NM_024426.4(WT1): c.1384C> T (p.Arg462Trp) single nucleotide variant Pathogenic rs121907900 GRCh37 Chromosome 11, 32413566: 32413566
2 WT1 NM_024426.4(WT1): c.1301G> A (p.Arg434His) single nucleotide variant Pathogenic rs121907901 GRCh37 Chromosome 11, 32414250: 32414250
3 WT1 NM_024426.4(WT1): c.1391A> G (p.Asp464Gly) single nucleotide variant Pathogenic rs121907902 GRCh37 Chromosome 11, 32413559: 32413559
4 WT1 NM_024426.4(WT1): c.1390G> A (p.Asp464Asn) single nucleotide variant Pathogenic rs28941778 GRCh37 Chromosome 11, 32413560: 32413560
5 WT1 NM_024426.4(WT1): c.1385G> C (p.Arg462Pro) single nucleotide variant Pathogenic rs121907903 GRCh37 Chromosome 11, 32413565: 32413565
6 WT1 NM_024426.4(WT1): c.1193G> A (p.Cys398Tyr) single nucleotide variant Pathogenic rs121907904 GRCh37 Chromosome 11, 32417859: 32417859
7 WT1 NM_024426.4(WT1): c.1432+5G> A single nucleotide variant Pathogenic rs587776576 GRCh38 Chromosome 11, 32391967: 32391967
8 WT1 NM_024426.4(WT1): c.1372C> T (p.Arg458Ter) single nucleotide variant Pathogenic rs121907909 GRCh37 Chromosome 11, 32413578: 32413578
9 WT1 NM_024426.4(WT1): c.1333C> T (p.His445Tyr) single nucleotide variant Pathogenic rs28942089 GRCh37 Chromosome 11, 32414218: 32414218
10 WT1 NM_024426.4(WT1): c.1282T> G (p.Cys428Gly) single nucleotide variant Pathogenic rs121907905 GRCh37 Chromosome 11, 32414269: 32414269
11 WT1 NM_024426.4(WT1): c.1288C> T (p.Arg430Ter) single nucleotide variant Pathogenic rs121907906 GRCh37 Chromosome 11, 32414263: 32414263
12 WT1 NM_024426.4(WT1): c.1323C> G (p.His441Gln) single nucleotide variant Pathogenic rs121907907 GRCh37 Chromosome 11, 32414228: 32414228
13 WT1 NM_001198551.1(WT1): c.161delC (p.Pro54Argfs) deletion Pathogenic rs1060501253 GRCh38 Chromosome 11, 32428031: 32428031

Copy number variations for Denys-Drash Syndrome from CNVD:

7
id CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 53562 11 31000000 36400000 Copy number WT1 Denys-drash syndrome
2 53587 11 31000000 36400000 Copy number WT1 Denys-drash syndrome

Expression for Denys-Drash Syndrome

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

Pathways for Denys-Drash Syndrome

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

id Super pathways Score Top Affiliating Genes
1 11.22 PAX2 PDGFA
2 10.9 BAX PDGFA
3 10.89 CD2AP NPHS1 NPHS2 PAX2 WT1
4 10.55 CD2AP NPHS1 NPHS2
5 10.5 CD2AP NPHS1

GO Terms for Denys-Drash Syndrome

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

id Name GO ID Score Top Affiliating Genes
1 slit diaphragm GO:0036057 8.62 NPHS1 NPHS2

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

(show all 15)
id Name GO ID Score Top Affiliating Genes
1 male gonad development GO:0008584 9.61 BAX NR5A1 WT1
2 response to wounding GO:0009611 9.55 BAX PDGFA
3 camera-type eye development GO:0043010 9.54 PAX2 WT1
4 branching involved in ureteric bud morphogenesis GO:0001658 9.52 PAX2 WT1
5 excretion GO:0007588 9.51 NPHS1 NPHS2
6 germ cell development GO:0007281 9.49 BAX WT1
7 adrenal gland development GO:0030325 9.48 NR5A1 WT1
8 tissue development GO:0009888 9.46 NR5A1 WT1
9 glomerular basement membrane development GO:0032836 9.4 NPHS1 WT1
10 mesenchymal to epithelial transition GO:0060231 9.37 PAX2 WT1
11 sex determination GO:0007530 9.32 NR5A1 WT1
12 positive regulation of male gonad development GO:2000020 9.26 NR5A1 WT1
13 metanephric mesenchyme development GO:0072075 9.16 PAX2 WT1
14 metanephric epithelium development GO:0072207 8.96 PAX2 WT1
15 negative regulation of female gonad development GO:2000195 8.62 NR5A1 WT1

Sources for Denys-Drash Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
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48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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