WS4A
MCID: WRD020
MIFTS: 47

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 58 13 41 74
Waardenburg Syndrome Type 4a 12 30 6 15
Shah-Waardenburg Syndrome 58 76 56
Ws4a 58 12 76
Waardenburg Syndrome with Hirschsprung Disease Type 4a 12 76
Waardenburg Syndrome Type Iva 12 76
Waardenburg-Shah Syndrome 58 76
Waardenburg Syndrome with Hirschsprung Disease, Type 4a 58
Hirschsprung Disease with Pigmentary Anomaly 76
Waardenburg Syndrome, Type Iva 58
Waardenburg Syndrome 4a 76
Ws4 58

Characteristics:

OMIM:

58
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:

33

Classifications:



Summaries for Waardenburg Syndrome, Type 4a

OMIM : 58 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 2e. 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 and eye, and related phenotypes are constipation and hearing impairment

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 : 76 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 32.2 EDN3 EDNRB MITF SOX10
2 waardenburg syndrome, type 2e 31.0 EDNRB MITF SOX10
3 waardenburg syndrome type 4 30.9 EDN3 EDNRB MITF SOX10
4 waardenburg syndrome, type 4b 30.9 EDN3 EDNRB MITF SOX10
5 waardenburg's syndrome 30.4 EDN3 EDNRB MITF RET SOX10
6 hirschsprung disease 1 28.8 EDN3 EDNRB MITF RET SOX10
7 waardenburg syndrome, type 4c 11.3
8 waardenburg syndrome, type 2b 11.1
9 waardenburg syndrome, type 2c 11.1
10 waardenburg syndrome, type 2d 11.1
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 sickle cell disease 10.2
18 dandy-walker complex 10.2
19 abcd syndrome 10.1 EDNRB EDNRB-AS1
20 hirschsprung disease 2 10.1 EDNRB EDNRB-AS1
21 multiple endocrine neoplasia, type iib 10.0 EDNRB RET
22 thyroid carcinoma, familial medullary 9.9 EDNRB RET
23 albinism, ocular, with late-onset sensorineural deafness 9.8 MITF SOX10
24 malignant spindle cell melanoma 9.8 MITF SOX10
25 intestinal pseudo-obstruction 9.8 EDNRB RET SOX10
26 breast angiosarcoma 9.8 MITF SOX10
27 tietz albinism-deafness syndrome 9.8 MITF SOX10
28 thyroid cancer, nonmedullary, 2 9.7 EDNRB RET
29 goldberg-shprintzen syndrome 9.7 EDN3 EDNRB RET
30 intestinal obstruction 9.7 EDN3 EDNRB RET
31 central hypoventilation syndrome, congenital 9.7 EDN3 EDNRB RET
32 familial renal papillary carcinoma 9.7 MITF RET
33 constipation 9.7 EDN3 EDNRB RET
34 neurofibroma 9.7 MITF SOX10
35 waardenburg syndrome, type 3 9.5 EDN3 MITF SOX10
36 dyschromatosis symmetrica hereditaria 9.5 EDN3 MITF SOX10
37 megacolon 9.4 EDN3 EDNRB RET SOX10
38 colonic disease 9.4 EDN3 EDNRB RET SOX10
39 cochlear disease 9.3 EDN3 EDNRB MITF SOX10
40 waardenburg syndrome, type 1 9.3 EDN3 EDNRB MITF SOX10
41 waardenburg syndrome, type 2a 9.0 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

Human phenotypes related to Waardenburg Syndrome, Type 4a:

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

Symptoms via clinical synopsis from OMIM:

58
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

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

47
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.8 EDN3 EDNRB MITF RET SOX10
2 embryo MP:0005380 9.72 EDN3 EDNRB MITF RET SOX10
3 digestive/alimentary MP:0005381 9.67 EDN3 EDNRB RET SOX10
4 integument MP:0010771 9.56 EDN3 EDNRB MITF SOX10
5 limbs/digits/tail MP:0005371 9.46 EDNRB MITF RET SOX10
6 nervous system MP:0003631 9.35 EDN3 EDNRB MITF RET SOX10
7 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 30 EDNRB

Anatomical Context for Waardenburg Syndrome, Type 4a

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

42
Skin, Eye

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:

76
# 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 28)
# 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_001201397.1(EDNRB): c.673G> A (p.Gly225Ser) single nucleotide variant Uncertain significance GRCh37 Chromosome 13, 78492306: 78492306
12 EDNRB NM_001201397.1(EDNRB): c.673G> A (p.Gly225Ser) single nucleotide variant Uncertain significance GRCh38 Chromosome 13, 77918171: 77918171
13 EDNRB NM_001201397.1(EDNRB): c.327C> A (p.Cys109Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 13, 78492652: 78492652
14 EDNRB NM_001201397.1(EDNRB): c.327C> A (p.Cys109Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 13, 77918517: 77918517
15 EDNRB NM_000115.4(EDNRB): c.973G> A (p.Val325Ile) single nucleotide variant Uncertain significance rs201437745 GRCh37 Chromosome 13, 78474768: 78474768
16 EDNRB NM_000115.4(EDNRB): c.973G> A (p.Val325Ile) single nucleotide variant Uncertain significance rs201437745 GRCh38 Chromosome 13, 77900633: 77900633
17 EDNRB NM_000115.4(EDNRB): c.550T> C (p.Ser184Pro) single nucleotide variant Likely pathogenic rs1555290659 GRCh37 Chromosome 13, 78477676: 78477676
18 EDNRB NM_000115.4(EDNRB): c.550T> C (p.Ser184Pro) single nucleotide variant Likely pathogenic rs1555290659 GRCh38 Chromosome 13, 77903541: 77903541
19 EDNRB NM_000115.4(EDNRB): c.521del (p.Cys174Leufs) deletion Pathogenic rs1458799604 GRCh37 Chromosome 13, 78477705: 78477705
20 EDNRB NM_000115.4(EDNRB): c.521del (p.Cys174Leufs) deletion Pathogenic rs1458799604 GRCh38 Chromosome 13, 77903570: 77903570
21 EDNRB NM_001201397.1(EDNRB): c.1061C> T (p.Ala354Val) single nucleotide variant Uncertain significance rs1212186974 GRCh38 Chromosome 13, 77903166: 77903166
22 EDNRB NM_001201397.1(EDNRB): c.1061C> T (p.Ala354Val) single nucleotide variant Uncertain significance rs1212186974 GRCh37 Chromosome 13, 78477301: 78477301
23 EDNRB NM_001201397.1(EDNRB): c.1048G> T (p.Val350Phe) single nucleotide variant not provided GRCh37 Chromosome 13, 78477314: 78477314
24 EDNRB NM_001201397.1(EDNRB): c.1048G> T (p.Val350Phe) single nucleotide variant not provided GRCh38 Chromosome 13, 77903179: 77903179
25 SOX10 NM_006941.3(SOX10): c.429-1G> A single nucleotide variant Pathogenic GRCh37 Chromosome 22, 38374143: 38374143
26 SOX10 NM_006941.3(SOX10): c.429-1G> A single nucleotide variant Pathogenic GRCh38 Chromosome 22, 37978136: 37978136
27 SOX10 NM_006941.3: c.1315_1329del deletion Pathogenic GRCh38 Chromosome 22, 37973568: 37973582
28 SOX10 NM_006941.3: c.1315_1329del deletion Pathogenic GRCh37 Chromosome 22, 38369574: 38369588

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 12.06 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 12)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription, DNA-templated GO:0045893 9.69 MITF RET SOX10
2 positive regulation of gene expression GO:0010628 9.67 MITF RET SOX10
3 negative regulation of apoptotic process GO:0043066 9.54 EDNRB MITF SOX10
4 pigmentation GO:0043473 9.48 EDNRB MITF
5 peripheral nervous system development GO:0007422 9.46 EDNRB SOX10
6 response to pain GO:0048265 9.43 EDNRB RET
7 vasoconstriction GO:0042310 9.4 EDN3 EDNRB
8 enteric nervous system development GO:0048484 9.33 EDNRB RET SOX10
9 vein smooth muscle contraction GO:0014826 9.32 EDN3 EDNRB
10 posterior midgut development GO:0007497 9.26 EDNRB RET
11 neural crest cell migration GO:0001755 9.26 EDN3 EDNRB RET SOX10
12 melanocyte differentiation GO:0030318 8.92 EDN3 EDNRB MITF SOX10

Sources for Waardenburg Syndrome, Type 4a

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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