WS4A
MCID: WRD020
MIFTS: 48

Waardenburg Syndrome, Type 4a (WS4A)

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

Aliases & Classifications for Waardenburg Syndrome, Type 4a

MalaCards integrated aliases for Waardenburg Syndrome, Type 4a:

Name: Waardenburg Syndrome, Type 4a 57 13 40 73
Waardenburg Syndrome Type 4a 12 29 6 15
Shah-Waardenburg Syndrome 57 75 55
Ws4a 57 12 75
Waardenburg Syndrome with Hirschsprung Disease Type 4a 12 75
Waardenburg Syndrome Type Iva 12 75
Waardenburg-Shah Syndrome 57 75
Waardenburg Syndrome with Hirschsprung Disease, Type 4a 57
Hirschsprung Disease with Pigmentary Anomaly 75
Waardenburg Syndrome, Type Iva 57
Waardenburg Syndrome 4a 75
Ws4 57

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive
autosomal dominant

Miscellaneous:
genetic heterogeneity
variable severity, intrafamilial
incomplete penetance of some features
both homozygous and heterozygous ednrb mutations have been found


HPO:

32

Classifications:



Summaries for Waardenburg Syndrome, Type 4a

OMIM : 57 Waardenburg syndrome type 4 (WS4), also known as Waardenburg-Shah syndrome, is an auditory-pigmentary syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes, congenital sensorineural hearing loss, and Hirschsprung disease (reviews by Read and Newton, 1997 and Pingault et al., 2010). WS type 4A is caused by mutation in the EDNRB gene (131244). (277580)

MalaCards based summary : Waardenburg Syndrome, Type 4a, also known as waardenburg syndrome type 4a, is related to peripheral demyelinating neuropathy, central dysmyelination, waardenburg syndrome, and hirschsprung disease and waardenburg syndrome type 4. An important gene associated with Waardenburg Syndrome, Type 4a is EDNRB (Endothelin Receptor Type B), and among its related pathways/superpathways are Pathways in cancer and Neural Crest Differentiation. Affiliated tissues include skin, eye and colon, and related phenotypes are nystagmus and ataxia

Disease Ontology : 12 A Waardenburg's syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes, congenital sensorineural hearing loss, and Hirschsprung disease that has material basis in heterozygous or homozygous mutation in the EDNRB gene on chromosome 13q22.

UniProtKB/Swiss-Prot : 75 Waardenburg syndrome 4A: A disorder characterized by the association of Waardenburg features (depigmentation and deafness) with the absence of enteric ganglia in the distal part of the intestine (Hirschsprung disease).

Related Diseases for Waardenburg Syndrome, Type 4a

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 4a via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 41)
# Related Disease Score Top Affiliating Genes
1 peripheral demyelinating neuropathy, central dysmyelination, waardenburg syndrome, and hirschsprung disease 32.5 EDN3 EDNRB MITF SOX10 SRY
2 waardenburg syndrome type 4 31.5 EDN3 EDNRB MITF SOX10
3 waardenburg syndrome, type 2e 31.4 EDNRB MITF SOX10
4 waardenburg syndrome, type 4b 31.2 EDN3 EDNRB MITF SOX10 SRY
5 waardenburg's syndrome 31.0 EDN3 EDNRB MITF RET SOX10
6 hirschsprung disease 1 29.4 EDN3 EDNRB MITF RET SOX10
7 waardenburg syndrome, type 4c 11.3
8 waardenburg syndrome, type 2b 11.0
9 waardenburg syndrome, type 2c 11.0
10 waardenburg syndrome, type 2d 11.0
11 down syndrome 10.2
12 aganglionosis, total intestinal 10.2
13 short bowel syndrome 10.2
14 microphthalmia 10.2
15 dermatitis 10.2
16 food allergy 10.2
17 dandy-walker complex 10.2
18 abcd syndrome 10.1 EDNRB EDNRB-AS1
19 hirschsprung disease 2 10.1 EDNRB EDNRB-AS1
20 albinism, ocular, with late-onset sensorineural deafness 10.0 MITF SOX10
21 malignant spindle cell melanoma 10.0 MITF SOX10
22 breast angiosarcoma 10.0 MITF SOX10
23 tietz albinism-deafness syndrome 10.0 MITF SOX10
24 campomelic dysplasia 9.9 SOX10 SRY
25 neurofibroma 9.9 MITF SOX10
26 multiple endocrine neoplasia, type iib 9.9 EDNRB RET
27 waardenburg syndrome, type 3 9.8 EDN3 MITF SOX10
28 dyschromatosis symmetrica hereditaria 9.8 EDN3 MITF SOX10
29 thyroid carcinoma, familial medullary 9.8 EDNRB RET
30 familial renal papillary carcinoma 9.8 MITF RET
31 intestinal pseudo-obstruction 9.8 EDNRB RET SOX10
32 goldberg-shprintzen syndrome 9.8 EDN3 EDNRB RET
33 intestinal obstruction 9.8 EDN3 EDNRB RET
34 central hypoventilation syndrome, congenital 9.8 EDN3 EDNRB RET
35 constipation 9.8 EDN3 EDNRB RET
36 thyroid cancer, nonmedullary, 2 9.7 EDNRB RET
37 cochlear disease 9.7 EDN3 EDNRB MITF SOX10
38 waardenburg syndrome, type 1 9.7 EDN3 EDNRB MITF SOX10
39 megacolon 9.6 EDN3 EDNRB RET SOX10
40 colonic disease 9.6 EDN3 EDNRB RET SOX10
41 waardenburg syndrome, type 2a 9.5 EDN3 EDNRB EDNRB-AS1 MITF SOX10

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



Diseases related to Waardenburg Syndrome, Type 4a

Symptoms & Phenotypes for Waardenburg Syndrome, Type 4a

Symptoms via clinical synopsis from OMIM:

57
Skin Nails Hair Skin:
hypopigmented skin patches

Skin Nails Hair Hair:
white forelock
white eyelashes
white eyebrows
premature graying

Abdomen Gastrointestinal:
hirschsprung disease
decreased myenteric and submucosal ganglia in the bowel

Head And Neck Eyes:
heterochromia iridis
bright blue irides
bicolored irides

Head And Neck Ears:
deafness, sensorineural


Clinical features from OMIM:

277580

Human phenotypes related to Waardenburg Syndrome, Type 4a:

32 (show all 29)
# Description HPO Frequency HPO Source Accession
1 nystagmus 32 HP:0000639
2 ataxia 32 HP:0001251
3 muscular hypotonia 32 HP:0001252
4 constipation 32 hallmark (90%) HP:0002019
5 hearing impairment 32 hallmark (90%) HP:0000365
6 global developmental delay 32 HP:0001263
7 wide nasal bridge 32 frequent (33%) HP:0000431
8 sensorineural hearing impairment 32 HP:0000407
9 abnormality of retinal pigmentation 32 occasional (7.5%) HP:0007703
10 abnormality of vision 32 hallmark (90%) HP:0000504
11 abdominal pain 32 frequent (33%) HP:0002027
12 hypopigmented skin patches 32 HP:0001053
13 intestinal obstruction 32 hallmark (90%) HP:0005214
14 prominent nasal bridge 32 frequent (33%) HP:0000426
15 underdeveloped nasal alae 32 frequent (33%) HP:0000430
16 telecanthus 32 occasional (7.5%) HP:0000506
17 heterochromia iridis 32 HP:0001100
18 premature graying of hair 32 hallmark (90%) HP:0002216
19 aganglionic megacolon 32 hallmark (90%) HP:0002251
20 blue irides 32 HP:0000635
21 white forelock 32 hallmark (90%) HP:0002211
22 synophrys 32 frequent (33%) HP:0000664
23 white eyebrow 32 hallmark (90%) HP:0002226
24 white eyelashes 32 hallmark (90%) HP:0002227
25 polyneuropathy 32 HP:0001271
26 leukodystrophy 32 HP:0002415
27 spastic paraparesis 32 HP:0002313
28 olfactory lobe agenesis 32 frequent (33%) HP:0001341
29 abnormal macular morphology 32 hallmark (90%) HP:0001103

MGI Mouse Phenotypes related to Waardenburg Syndrome, Type 4a:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 digestive/alimentary MP:0005381 9.56 EDN3 EDNRB RET SOX10
2 embryo MP:0005380 9.55 EDN3 EDNRB MITF RET SOX10
3 limbs/digits/tail MP:0005371 9.26 EDNRB MITF RET SOX10
4 pigmentation MP:0001186 8.92 EDN3 EDNRB MITF SOX10

Drugs & Therapeutics for Waardenburg Syndrome, Type 4a

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

Genetic Tests for Waardenburg Syndrome, Type 4a

Genetic tests related to Waardenburg Syndrome, Type 4a:

# Genetic test Affiliating Genes
1 Waardenburg Syndrome Type 4a 29 EDNRB

Anatomical Context for Waardenburg Syndrome, Type 4a

MalaCards organs/tissues related to Waardenburg Syndrome, Type 4a:

41
Skin, Eye, Colon, Thyroid

Publications for Waardenburg Syndrome, Type 4a

Articles related to Waardenburg Syndrome, Type 4a:

(show all 12)
# Title Authors Year
1
Shah-Waardenburg syndrome: a case highlighting the importance of a holistic approach to assessing a child. ( 29275389 )
2017
2
A novel mutation in the endothelin B receptor gene in a moroccan family with shah-waardenburg syndrome. ( 25852447 )
2015
3
Does short bowel syndrome increase the risk of food allergy and eosinophilic gastrointestinal disease? Observations in Shah-Waardenburg syndrome. ( 23177999 )
2013
4
Shah-Waardenburg syndrome. ( 23565307 )
2013
5
Anesthetic management of Shah-Waardenburg syndrome: Experience of two cases and review of literature. ( 22754447 )
2012
6
Shah-Waardenburg syndrome. ( 18319036 )
2008
7
Shah-Waardenburg syndrome and PCWH associated with SOX10 mutations: a case report and review of the literature. ( 16504559 )
2006
8
Shah Waardenburg syndrome. ( 16735772 )
2006
9
Shah-Waardenburg syndrome and Dandy-Walker malformation: an autopsy report. ( 12365727 )
2002
10
A novel mutation in the endothelin B receptor gene in a patient with Shah-Waardenburg syndrome and Down syndrome. ( 11565556 )
2001
11
Mutation of the endothelin-3 gene in the Waardenburg-Hirschsprung disease (Shah-Waardenburg syndrome). ( 8630502 )
1996
12
A homozygous mutation in the endothelin-3 gene associated with a combined Waardenburg type 2 and Hirschsprung phenotype (Shah- Waardenburg syndrome). ( 8630503 )
1996

Variations for Waardenburg Syndrome, Type 4a

UniProtKB/Swiss-Prot genetic disease variations for Waardenburg Syndrome, Type 4a:

75
# Symbol AA change Variation ID SNP ID
1 EDNRB p.Ala183Gly VAR_003470 rs104894388
2 EDNRB p.Phe292Leu VAR_015294

ClinVar genetic disease variations for Waardenburg Syndrome, Type 4a:

6 (show all 20)
# Gene Variation Type Significance SNP ID Assembly Location
1 EDNRB NM_000115.4(EDNRB): c.828G> T (p.Trp276Cys) single nucleotide variant Pathogenic rs104894387 GRCh37 Chromosome 13, 78475316: 78475316
2 EDNRB NM_000115.4(EDNRB): c.828G> T (p.Trp276Cys) single nucleotide variant Pathogenic rs104894387 GRCh38 Chromosome 13, 77901181: 77901181
3 EDNRB NM_000115.4(EDNRB): c.548C> G (p.Ala183Gly) single nucleotide variant Pathogenic rs104894388 GRCh37 Chromosome 13, 78477678: 78477678
4 EDNRB NM_000115.4(EDNRB): c.548C> G (p.Ala183Gly) single nucleotide variant Pathogenic rs104894388 GRCh38 Chromosome 13, 77903543: 77903543
5 EDNRB NM_000115.4(EDNRB): c.914G> A (p.Ser305Asn) single nucleotide variant risk factor rs5352 GRCh37 Chromosome 13, 78475230: 78475230
6 EDNRB NM_000115.4(EDNRB): c.914G> A (p.Ser305Asn) single nucleotide variant risk factor rs5352 GRCh38 Chromosome 13, 77901095: 77901095
7 EDNRB NM_000115.4(EDNRB): c.757C> T (p.Arg253Ter) single nucleotide variant Pathogenic rs104894390 GRCh37 Chromosome 13, 78477335: 78477335
8 EDNRB NM_000115.4(EDNRB): c.757C> T (p.Arg253Ter) single nucleotide variant Pathogenic rs104894390 GRCh38 Chromosome 13, 77903200: 77903200
9 EDNRB NM_000115.4(EDNRB): c.601C> T (p.Arg201Ter) single nucleotide variant Pathogenic rs104894391 GRCh37 Chromosome 13, 78477491: 78477491
10 EDNRB NM_000115.4(EDNRB): c.601C> T (p.Arg201Ter) single nucleotide variant Pathogenic rs104894391 GRCh38 Chromosome 13, 77903356: 77903356
11 EDNRB NM_000115.4(EDNRB): c.973G> A (p.Val325Ile) single nucleotide variant Uncertain significance rs201437745 GRCh37 Chromosome 13, 78474768: 78474768
12 EDNRB NM_000115.4(EDNRB): c.973G> A (p.Val325Ile) single nucleotide variant Uncertain significance rs201437745 GRCh38 Chromosome 13, 77900633: 77900633
13 EDNRB NM_000115.4(EDNRB): c.550T> C (p.Ser184Pro) single nucleotide variant Likely pathogenic GRCh37 Chromosome 13, 78477676: 78477676
14 EDNRB NM_000115.4(EDNRB): c.550T> C (p.Ser184Pro) single nucleotide variant Likely pathogenic GRCh38 Chromosome 13, 77903541: 77903541
15 EDNRB NM_000115.4(EDNRB): c.521del (p.Cys174Leufs) deletion Pathogenic GRCh37 Chromosome 13, 78477705: 78477705
16 EDNRB NM_000115.4(EDNRB): c.521del (p.Cys174Leufs) deletion Pathogenic GRCh38 Chromosome 13, 77903570: 77903570
17 EDNRB NM_001201397.1(EDNRB): c.1061C> T (p.Ala354Val) single nucleotide variant Uncertain significance GRCh38 Chromosome 13, 77903166: 77903166
18 EDNRB NM_001201397.1(EDNRB): c.1061C> T (p.Ala354Val) single nucleotide variant Uncertain significance GRCh37 Chromosome 13, 78477301: 78477301
19 EDNRB NM_001201397.1(EDNRB): c.1048G> T (p.Val350Phe) single nucleotide variant not provided rs77132068 GRCh37 Chromosome 13, 78477314: 78477314
20 EDNRB NM_001201397.1(EDNRB): c.1048G> T (p.Val350Phe) single nucleotide variant not provided rs77132068 GRCh38 Chromosome 13, 77903179: 77903179

Expression for Waardenburg Syndrome, Type 4a

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

Pathways for Waardenburg Syndrome, Type 4a

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

# Super pathways Score Top Affiliating Genes
1 12.05 EDNRB MITF RET
2 11.27 MITF SOX10
3 10.68 EDN3 EDNRB
4 10.24 MITF SOX10

GO Terms for Waardenburg Syndrome, Type 4a

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

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 cell differentiation GO:0030154 9.81 MITF RET SOX10 SRY
2 positive regulation of transcription, DNA-templated GO:0045893 9.73 MITF RET SOX10 SRY
3 positive regulation of gene expression GO:0010628 9.7 MITF RET SOX10
4 negative regulation of apoptotic process GO:0043066 9.67 EDNRB MITF RET SOX10
5 pigmentation GO:0043473 9.49 EDNRB MITF
6 peripheral nervous system development GO:0007422 9.48 EDNRB SOX10
7 response to pain GO:0048265 9.46 EDNRB RET
8 vasoconstriction GO:0042310 9.4 EDN3 EDNRB
9 enteric nervous system development GO:0048484 9.33 EDNRB RET SOX10
10 vein smooth muscle contraction GO:0014826 9.32 EDN3 EDNRB
11 posterior midgut development GO:0007497 9.26 EDNRB RET
12 neural crest cell migration GO:0001755 9.26 EDN3 EDNRB RET SOX10
13 melanocyte differentiation GO:0030318 8.92 EDN3 EDNRB MITF SOX10

Molecular functions related to Waardenburg Syndrome, Type 4a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding GO:0003705 8.8 MITF SOX10 SRY

Sources for Waardenburg Syndrome, Type 4a

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 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 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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