WS4
MCID: WRD010
MIFTS: 31

Waardenburg Syndrome Type 4 (WS4)

Categories: Ear diseases, Eye diseases, Fetal diseases, Gastrointestinal diseases, Genetic diseases, Rare diseases, Skin diseases

Aliases & Classifications for Waardenburg Syndrome Type 4

MalaCards integrated aliases for Waardenburg Syndrome Type 4:

Name: Waardenburg Syndrome Type 4 20 70
Hirschsprung Disease with Pigmentary Anomaly 20 6
Waardenburg-Hirschsprung Syndrome 20
Waardenburg-Hirschsprung Disease 20
Waardenburg Syndrome, Type 4a 70
Waardenburg-Shah Syndrome 20
Shah-Waardenburg Syndrome 20
Ws4 20

Classifications:



External Ids:

UMLS 70 C1848519 C3469510

Summaries for Waardenburg Syndrome Type 4

GARD : 20 Waardenburg syndrome type 4, also known as Waardenburg-Shah syndrome, is a genetic condition that can cause hearing loss ; changes in coloring (pigmentation) of the hair, skin, and eyes; and Hirschsprung disease, an intestinal disorder that causes severe constipation or blockage of the intestine. Waardenburg syndrome type 4 is further divided into types 4A, 4B, and 4C based on their genetic cause. Type 4A is caused by mutations in the EDNRB gene, m utations in EDN3 cause 4B, and mutations in SOX10 cause type 4C. This condition is usually inherited in an autosomal dominant fashion; however, some cases of type 4 appear to have an autosomal recessive pattern of inheritance.

MalaCards based summary : Waardenburg Syndrome Type 4, also known as hirschsprung disease with pigmentary anomaly, is related to waardenburg syndrome, type 4b and waardenburg syndrome, type 2d. An important gene associated with Waardenburg Syndrome Type 4 is EDNRB (Endothelin Receptor Type B), and among its related pathways/superpathways are Neural Crest Differentiation and Endothelins. Affiliated tissues include eye and skin, and related phenotype is pigmentation.

Related Diseases for Waardenburg Syndrome Type 4

Diseases in the Waardenburg's Syndrome family:

Waardenburg Syndrome, Type 3 Waardenburg Syndrome, Type 1
Waardenburg Syndrome, Type 2a Waardenburg Syndrome, Type 4a
Waardenburg Syndrome, Type 2b Waardenburg Syndrome, Type 2c
Waardenburg Syndrome, Type 2d Waardenburg Syndrome, Type 2e
Waardenburg Syndrome, Type 4b Waardenburg Syndrome, Type 4c
Waardenburg Syndrome Type 4

Diseases related to Waardenburg Syndrome Type 4 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 70)
# Related Disease Score Top Affiliating Genes
1 waardenburg syndrome, type 4b 31.2 SOX10 MITF EDNRB EDN3
2 waardenburg syndrome, type 2d 31.1 SOX10 MITF EDNRB
3 waardenburg syndrome, type 2b 31.1 SOX10 MITF EDN3
4 waardenburg syndrome, type 2c 30.8 SOX10 MITF EDNRB EDN3
5 waardenburg syndrome, type 4a 30.8 SOX10 POLR2F MITF EDNRB-AS1 EDNRB EDN3
6 waardenburg syndrome, type 4c 30.7 SOX10 POLR2F MITF EDNRB EDN3
7 intestinal obstruction 30.0 EDNRB EDN3
8 megacolon 29.8 SOX10 EDNRB EDN3
9 waardenburg's syndrome 29.7 SOX10 POLR2F MITF EDNRB EDN3
10 waardenburg syndrome, type 1 29.2 SOX10 MITF EDNRB EDN3
11 hirschsprung disease 1 29.0 SOX10 POLR2F MITF EDNRB-AS1 EDNRB EDN3
12 waardenburg syndrome, type 2e 29.0 SOX10 POLR2F MITF EDNRB EDN3
13 peripheral demyelinating neuropathy, central dysmyelination, waardenburg syndrome, and hirschsprung disease 29.0 SOX10 POLR2F MITF EDNRB EDN3
14 catatrichy 10.3
15 branchiootic syndrome 1 10.3
16 sensorineural hearing loss 10.2
17 down syndrome 10.1
18 distal arthrogryposis 10.1
19 cholelithiasis 10.1
20 leukodystrophy 10.1
21 short bowel syndrome 10.1
22 hydrocephalus 10.1
23 acute chest syndrome 10.1
24 dermatitis 10.1
25 irritant dermatitis 10.1
26 hemoglobinopathy 10.1
27 food allergy 10.1
28 mutism 10.1
29 peripheral nervous system disease 10.1
30 neuropathy 10.1
31 sickle cell disease 10.1
32 avascular necrosis 10.1
33 tubb4a-related leukodystrophy 10.1
34 gallbladder melanoma 10.1 SOX10 MITF
35 aganglionosis, total intestinal 10.0 EDNRB-AS1 EDNRB
36 malignant choroid melanoma 10.0 SOX10 MITF
37 mowat-wilson syndrome 10.0 SOX10 EDNRB
38 pulmonary hypertension, primary, 4 10.0
39 goldberg-shprintzen syndrome 10.0 EDNRB EDN3
40 malignant spindle cell melanoma 10.0 SOX10 MITF
41 mitochondrial dna depletion syndrome 12a 10.0 EDNRB-AS1 EDNRB
42 retinoblastoma 10.0
43 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.0
44 microphthalmia 10.0
45 constipation 10.0
46 demyelinating polyneuropathy 10.0
47 hypotonia 10.0
48 congenital amyoplasia 10.0
49 pigmentation anomaly of the skin 10.0
50 hirschsprung disease 2 10.0 EDNRB-AS1 EDNRB

Graphical network of the top 20 diseases related to Waardenburg Syndrome Type 4:



Diseases related to Waardenburg Syndrome Type 4

Symptoms & Phenotypes for Waardenburg Syndrome Type 4

MGI Mouse Phenotypes related to Waardenburg Syndrome Type 4:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 pigmentation MP:0001186 8.92 EDN3 EDNRB MITF SOX10

Drugs & Therapeutics for Waardenburg Syndrome Type 4

Search Clinical Trials , NIH Clinical Center for Waardenburg Syndrome Type 4

Genetic Tests for Waardenburg Syndrome Type 4

Anatomical Context for Waardenburg Syndrome Type 4

MalaCards organs/tissues related to Waardenburg Syndrome Type 4:

40
Eye, Skin

Publications for Waardenburg Syndrome Type 4

Articles related to Waardenburg Syndrome Type 4:

(show all 23)
# Title Authors PMID Year
1
Novel nonsense mutation of the endothelin-B receptor gene in a family with Waardenburg-Hirschsprung disease. 6
10528251 1999
2
Mutation of the endothelin-receptor B gene in Waardenburg-Hirschsprung disease. 6
8634719 1995
3
A missense mutation of the endothelin-B receptor gene in multigenic Hirschsprung's disease. 6
8001158 1994
4
Genetic characterization of a patient with an unusual presentation of Waardenburg syndrome Type 4 and retinoblastoma. 61
32672397 2021
5
Outcome of Children With Intestinal Failure Due to Waardenburg Syndrome From an Intestinal Transplant Center: A Case Series. 61
32967600 2020
6
A homozygous MITF mutation leads to familial Waardenburg syndrome type 4. 61
30549420 2019
7
The additional genetic diagnosis of homozygous sickle cell disease in a patient with Waardenburg-Shah syndrome: a case report. 61
30636638 2019
8
Case of Waardenburg Shah syndrome in a family with review of literature. 61
30559775 2018
9
A de novo deletion mutation in SOX10 in a Chinese family with Waardenburg syndrome type 4. 61
28128317 2017
10
A Scoring System to Predict the Severity of Hirschsprung Disease at Diagnosis and Its Correlation With Molecular Genetics. 61
28276298 2017
11
Upregulation of the Nr2f1-A830082K12Rik gene pair in murine neural crest cells results in a complex phenotype reminiscent of Waardenburg syndrome type 4. 61
27585883 2016
12
An impairment of long distance SOX10 regulatory elements underlies isolated Hirschsprung disease. 61
24357527 2014
13
Waardenburg syndrome type 4: report of two new cases caused by SOX10 mutations in Spain. 61
24311220 2014
14
Pediatric case report: clinical profile of a patient with PCWH with p.Q377X nonsense mutation in the SOX10 gene. 61
22963253 2012
15
Alu-mediated deletion of SOX10 regulatory elements in Waardenburg syndrome type 4. 61
22378281 2012
16
SOX10 mutation with peripheral amyelination and developmental disturbance of axons. 61
22246888 2012
17
Genetic background strongly modifies the severity of symptoms of Hirschsprung disease, but not hearing loss in rats carrying Ednrb(sl) mutations. 61
21915282 2011
18
A deletion in the endothelin-B receptor gene is responsible for the Waardenburg syndrome-like phenotypes of WS4 mice. 61
17090968 2006
19
The Waardenburg syndrome type 4 gene, SOX10, is a novel tumor-associated antigen identified in a patient with a dramatic response to immunotherapy. 61
12036907 2002
20
A mouse model of Waardenburg syndrome type 4 with a new spontaneous mutation of the endothelin-B receptor gene. 61
11773966 2002
21
Regulation of the microphthalmia-associated transcription factor gene by the Waardenburg syndrome type 4 gene, SOX10. 61
10938265 2000
22
Neurological phenotype in Waardenburg syndrome type 4 correlates with novel SOX10 truncating mutations and expression in developing brain. 61
10762540 2000
23
The Sox10(Dom) mouse: modeling the genetic variation of Waardenburg-Shah (WS4) syndrome. 61
10077527 1999

Variations for Waardenburg Syndrome Type 4

ClinVar genetic disease variations for Waardenburg Syndrome Type 4:

6 (show all 17)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 POLR2F , SOX10 NM_006941.3(SOX10):c.429-1G>A SNV Pathogenic 590850 rs1569169328 GRCh37: 22:38374143-38374143
GRCh38: 22:37978136-37978136
2 POLR2F , SOX10 NM_006941.4(SOX10):c.1315_1329del (p.Ile439_Ser443del) Deletion Pathogenic 620636 rs1569167515 GRCh37: 22:38369574-38369588
GRCh38: 22:37973567-37973581
3 EDNRB-AS1 , EDNRB NM_001122659.3(EDNRB):c.521del (p.Cys174fs) Deletion Pathogenic 547293 rs1458799604 GRCh37: 13:78477705-78477705
GRCh38: 13:77903570-77903570
4 EDNRB-AS1 , EDNRB NM_001122659.3(EDNRB):c.757C>T (p.Arg253Ter) SNV Pathogenic 16639 rs104894390 GRCh37: 13:78477335-78477335
GRCh38: 13:77903200-77903200
5 EDNRB-AS1 , EDNRB NM_001122659.3(EDNRB):c.548C>G (p.Ala183Gly) SNV Pathogenic 16634 rs104894388 GRCh37: 13:78477678-78477678
GRCh38: 13:77903543-77903543
6 EDNRB-AS1 , EDNRB NM_001122659.3(EDNRB):c.828G>T (p.Trp276Cys) SNV Pathogenic 16633 rs104894387 GRCh37: 13:78475316-78475316
GRCh38: 13:77901181-77901181
7 EDNRB-AS1 , EDNRB NM_001122659.3(EDNRB):c.601C>T (p.Arg201Ter) SNV Pathogenic 16640 rs104894391 GRCh37: 13:78477491-78477491
GRCh38: 13:77903356-77903356
8 EDNRB NM_001122659.3(EDNRB):c.57C>A (p.Cys19Ter) SNV Pathogenic/Likely pathogenic 545012 rs768126403 GRCh37: 13:78492652-78492652
GRCh38: 13:77918517-77918517
9 EDNRB-AS1 , EDNRB NM_001122659.3(EDNRB):c.777del (p.Val260fs) Deletion Likely pathogenic 1064869 GRCh37: 13:78477315-78477315
GRCh38: 13:77903180-77903180
10 EDNRB-AS1 , EDNRB NM_001122659.3(EDNRB):c.550T>C (p.Ser184Pro) SNV Likely pathogenic 547294 rs1555290659 GRCh37: 13:78477676-78477676
GRCh38: 13:77903541-77903541
11 EDNRB-AS1 , EDNRB NM_001122659.3(EDNRB):c.1103A>T (p.Asp368Val) SNV Uncertain significance 1064870 GRCh37: 13:78474085-78474085
GRCh38: 13:77899950-77899950
12 EDNRB NM_001122659.3(EDNRB):c.-26G>A SNV Uncertain significance 225346 rs2070591 GRCh37: 13:78492734-78492734
GRCh38: 13:77918599-77918599
13 EDNRB NM_001122659.3(EDNRB):c.403G>A (p.Gly135Ser) SNV Uncertain significance 545011 rs760677132 GRCh37: 13:78492306-78492306
GRCh38: 13:77918171-77918171
14 EDNRB-AS1 , EDNRB NM_001122659.3(EDNRB):c.973G>A (p.Val325Ile) SNV Uncertain significance 547295 rs201437745 GRCh37: 13:78474768-78474768
GRCh38: 13:77900633-77900633
15 EDNRB-AS1 , EDNRB NM_001122659.3(EDNRB):c.791C>T (p.Ala264Val) SNV Uncertain significance 547950 rs1212186974 GRCh37: 13:78477301-78477301
GRCh38: 13:77903166-77903166
16 EDNRB-AS1 , EDNRB NM_001122659.3(EDNRB):c.914G>A (p.Ser305Asn) SNV Likely benign 16638 rs5352 GRCh37: 13:78475230-78475230
GRCh38: 13:77901095-77901095
17 EDNRB-AS1 , EDNRB NM_001122659.3(EDNRB):c.778G>T (p.Val260Phe) SNV not provided 585146 rs77132068 GRCh37: 13:78477314-78477314
GRCh38: 13:77903179-77903179

Expression for Waardenburg Syndrome Type 4

Search GEO for disease gene expression data for Waardenburg Syndrome Type 4.

Pathways for Waardenburg Syndrome Type 4

Pathways related to Waardenburg Syndrome Type 4 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.16 SOX10 MITF
2 10.68 EDNRB EDN3
3 10.24 SOX10 MITF

GO Terms for Waardenburg Syndrome Type 4

Biological processes related to Waardenburg Syndrome Type 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 negative regulation of apoptotic process GO:0043066 9.63 SOX10 MITF EDNRB
2 transcription elongation from RNA polymerase II promoter GO:0006368 9.43 SOX10 POLR2F
3 pigmentation GO:0043473 9.4 MITF EDNRB
4 peripheral nervous system development GO:0007422 9.37 SOX10 EDNRB
5 vasoconstriction GO:0042310 9.32 EDNRB EDN3
6 enteric nervous system development GO:0048484 9.26 SOX10 EDNRB
7 vein smooth muscle contraction GO:0014826 9.16 EDNRB EDN3
8 neural crest cell migration GO:0001755 9.13 SOX10 EDNRB EDN3
9 melanocyte differentiation GO:0030318 8.92 SOX10 MITF EDNRB EDN3

Sources for Waardenburg Syndrome Type 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....