WS4B
MCID: WRD019
MIFTS: 46

Waardenburg Syndrome, Type 4b (WS4B)

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

Aliases & Classifications for Waardenburg Syndrome, Type 4b

MalaCards integrated aliases for Waardenburg Syndrome, Type 4b:

Name: Waardenburg Syndrome, Type 4b 58 13 41 74
Waardenburg Syndrome Type 4b 12 30 6 15
Ws4b 58 12 76
Waardenburg Syndrome with Hirschsprung Disease Type 4b 12 76
Waardenburg Syndrome Type Ivb 12 76
Waardenburg Syndrome, Type 4b, with Hirschsprung Disease 58
Hirschsprung Disease with Pigmentary Anomaly 76
Waardenburg Syndrome, Type Ivb 58
Waardenburg Syndrome, Type 4a 74
Waardenburg-Shah Syndrome 76
Shah-Waardenburg Syndrome 76
Waardenburg Syndrome 4b 76

Characteristics:

OMIM:

58
Inheritance:
autosomal recessive
autosomal dominant

Miscellaneous:
genetic heterogeneity
variable severity, intrafamilial
incomplete penetrance of some features
both homozygous and heterozygous edn3 mutations have been found


HPO:

33

Classifications:



Summaries for Waardenburg Syndrome, Type 4b

OMIM : 58 Waardenburg syndrome type 4 is an auditory-pigmentary syndrome characterized by pigmentary abnormalities of the eye, deafness, and Hirschsprung disease (review by Read and Newton, 1997). WS type 4B is caused by mutation in the EDN3 gene (131242). WS type 4 is genetically heterogeneous (see WS4A; 277580). For a description of other clinical variants of Waardenburg syndrome, see WS1 (193500), WS2 (193510), and WS3 (148820). (613265)

MalaCards based summary : Waardenburg Syndrome, Type 4b, also known as waardenburg syndrome type 4b, is related to waardenburg syndrome, type 4a and waardenburg syndrome type 4. An important gene associated with Waardenburg Syndrome, Type 4b is EDN3 (Endothelin 3), and among its related pathways/superpathways are Regulation of Wnt-mediated beta catenin signaling and target gene transcription and Regulation of retinoblastoma protein. Affiliated tissues include eye, skin and kidney, and related phenotypes are sensorineural hearing impairment and hypopigmented skin patches

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 homozygous and heterozygous mutation in the EDN3 gene on chromosome 20q13.

UniProtKB/Swiss-Prot : 76 Waardenburg syndrome 4B: 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 4b

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

(show all 36)
# Related Disease Score Top Affiliating Genes
1 waardenburg syndrome, type 4a 32.1 EDN3 EDNRB MITF SOX10
2 waardenburg syndrome type 4 32.0 EDN3 EDNRB MITF SOX10
3 peripheral demyelinating neuropathy, central dysmyelination, waardenburg syndrome, and hirschsprung disease 31.4 EDN3 EDNRB MITF PAX3 SNAI2 SOX10
4 waardenburg's syndrome 30.2 EDN3 EDNRB MITF PAX3 SNAI2 SOX10
5 hirschsprung disease 1 28.9 EDN3 EDNRB MITF PAX3 SOX10
6 waardenburg syndrome, type 4c 11.8
7 down syndrome 10.2
8 aganglionosis, total intestinal 10.2
9 short bowel syndrome 10.2
10 microphthalmia 10.2
11 dermatitis 10.2
12 food allergy 10.2
13 sickle cell disease 10.2
14 dandy-walker complex 10.2
15 hermansky-pudlak syndrome 1 10.0 PAX3 SOX10
16 albinism, ocular, with late-onset sensorineural deafness 10.0 MITF SOX10
17 malignant spindle cell melanoma 10.0 MITF SOX10
18 cellular schwannoma 10.0 PAX3 SOX10
19 breast angiosarcoma 10.0 MITF SOX10
20 childhood kidney cell carcinoma 9.9 MITF PAX3
21 neurofibroma 9.9 MITF SOX10
22 goldberg-shprintzen syndrome 9.9 EDN3 EDNRB
23 intestinal pseudo-obstruction 9.7 EDNRB SOX10
24 intestinal obstruction 9.7 EDN3 EDNRB
25 tietz albinism-deafness syndrome 9.7 MITF PAX3 SOX10
26 central hypoventilation syndrome, congenital 9.7 EDN3 EDNRB
27 piebald trait 9.7 MITF PAX3 SNAI2
28 megacolon 9.6 EDN3 EDNRB SOX10
29 colonic disease 9.6 EDN3 EDNRB SOX10
30 constipation 9.6 EDN3 EDNRB
31 waardenburg syndrome, type 3 9.5 EDN3 MITF PAX3 SOX10
32 dyschromatosis symmetrica hereditaria 9.5 EDN3 MITF PAX3 SOX10
33 waardenburg syndrome, type 2e 9.3 EDNRB MITF SNAI2 SOX10
34 cochlear disease 9.0 EDN3 EDNRB MITF SNAI2 SOX10
35 waardenburg syndrome, type 2a 9.0 EDN3 EDNRB MITF SNAI2 SOX10
36 waardenburg syndrome, type 1 8.7 EDN3 EDNRB MITF PAX3 SNAI2 SOX10

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



Diseases related to Waardenburg Syndrome, Type 4b

Symptoms & Phenotypes for Waardenburg Syndrome, Type 4b

Human phenotypes related to Waardenburg Syndrome, Type 4b:

33 (show all 9)
# Description HPO Frequency HPO Source Accession
1 sensorineural hearing impairment 33 HP:0000407
2 hypopigmented skin patches 33 HP:0001053
3 heterochromia iridis 33 HP:0001100
4 premature graying of hair 33 HP:0002216
5 aganglionic megacolon 33 HP:0002251
6 blue irides 33 HP:0000635
7 white forelock 33 HP:0002211
8 white eyebrow 33 HP:0002226
9 white eyelashes 33 HP:0002227

Symptoms via clinical synopsis from OMIM:

58
Skin Nails Hair Skin:
hypopigmented skin patches

Head And Neck Ears:
deafness, sensorineural

Head And Neck Eyes:
bright blue irides
hypopigmented irides

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

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

Clinical features from OMIM:

613265

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

47 (show all 11)
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.97 EDN3 EDNRB MITF PAX3 SNAI2 SOX10
2 embryo MP:0005380 9.91 EDN3 EDNRB MITF PAX3 SNAI2 SOX10
3 digestive/alimentary MP:0005381 9.85 EDN3 EDNRB PAX3 SNAI2 SOX10
4 integument MP:0010771 9.85 EDN3 EDNRB MITF PAX3 SNAI2 SOX10
5 endocrine/exocrine gland MP:0005379 9.8 EDNRB MITF PAX3 SNAI2 SOX10
6 craniofacial MP:0005382 9.78 EDNRB MITF PAX3 SNAI2
7 mortality/aging MP:0010768 9.73 EDN3 EDNRB MITF PAX3 SNAI2 SOX10
8 nervous system MP:0003631 9.63 EDN3 EDNRB MITF PAX3 SNAI2 SOX10
9 limbs/digits/tail MP:0005371 9.62 EDNRB MITF PAX3 SOX10
10 pigmentation MP:0001186 9.43 EDN3 EDNRB MITF PAX3 SNAI2 SOX10
11 vision/eye MP:0005391 8.92 EDNRB MITF PAX3 SNAI2

Drugs & Therapeutics for Waardenburg Syndrome, Type 4b

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

Genetic Tests for Waardenburg Syndrome, Type 4b

Genetic tests related to Waardenburg Syndrome, Type 4b:

# Genetic test Affiliating Genes
1 Waardenburg Syndrome Type 4b 30 EDN3

Anatomical Context for Waardenburg Syndrome, Type 4b

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

42
Eye, Skin, Kidney, Colon

Publications for Waardenburg Syndrome, Type 4b

Articles related to Waardenburg Syndrome, Type 4b:

(show all 12)
# Title Authors Year
1
The additional genetic diagnosis of homozygous sickle cell disease in a patient with Waardenburg-Shah syndrome: a case report. ( 30636638 )
2019
2
A recalcitrant case of Jacquet erosive diaper dermatitis after surgery for Hirschsprung disease in a boy with Waardenburg-Shah syndrome. ( 30142718 )
2018
3
Perturbation of the consensus activation site of endothelin-3 leads to Waardenburg syndrome type IV. ( 20583152 )
2010
4
Genetic and phenotypic heterogeneity in two novel cases of Waardenburg syndrome type IV. ( 19764030 )
2009
5
Clinical variability of Waardenburg-Shah syndrome in patients with proximal 13q deletion syndrome including the endothelin-B receptor locus. ( 19764031 )
2009
6
Long segment Hirschsprung's disease in the Waardenburg-Shah syndrome. ( 12811477 )
2003
7
A heterozygous endothelin 3 mutation in Waardenburg-Hirschsprung disease: is there a dosage effect of EDN3/EDNRB gene mutations on neurocristopathy phenotypes? ( 11303518 )
2001
8
Novel mutations of SOX10 suggest a dominant negative role in Waardenburg-Shah syndrome. ( 11546831 )
2001
9
Direct regulation of the Microphthalmia promoter by Sox10 links Waardenburg-Shah syndrome (WS4)-associated hypopigmentation and deafness to WS2. ( 10973953 )
2000
10
Near-total intestinal aganglionosis in the Waardenburg-Shah syndrome. ( 10626872 )
1999
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 4b

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

76
# Symbol AA change Variation ID SNP ID
1 EDN3 p.Cys159Phe VAR_002353 rs74315384
2 EDN3 p.Tyr127Cys VAR_015238 rs752400458

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

6 (show all 16)
# Gene Variation Type Significance SNP ID Assembly Location
1 EDN3 NM_207034.3(EDN3): c.262_263delGCinsT (p.Ala88Serfs) indel Pathogenic GRCh37 Chromosome 20, 57876674: 57876675
2 EDN3 NM_207034.3(EDN3): c.262_263delGCinsT (p.Ala88Serfs) indel Pathogenic GRCh38 Chromosome 20, 59301619: 59301620
3 EDN3 NM_207034.2(EDN3): c.476G> T (p.Cys159Phe) single nucleotide variant Pathogenic rs74315384 GRCh37 Chromosome 20, 57896182: 57896182
4 EDN3 NM_207034.2(EDN3): c.476G> T (p.Cys159Phe) single nucleotide variant Pathogenic rs74315384 GRCh38 Chromosome 20, 59321127: 59321127
5 EDN3 NM_207034.2(EDN3): c.507C> A (p.Cys169Ter) single nucleotide variant Pathogenic rs74315385 GRCh37 Chromosome 20, 57896213: 57896213
6 EDN3 NM_207034.2(EDN3): c.507C> A (p.Cys169Ter) single nucleotide variant Pathogenic rs74315385 GRCh38 Chromosome 20, 59321158: 59321158
7 EDN3 NM_207034.2(EDN3): c.335A> G (p.His112Arg) single nucleotide variant Pathogenic rs267606778 GRCh37 Chromosome 20, 57876747: 57876747
8 EDN3 NM_207034.2(EDN3): c.335A> G (p.His112Arg) single nucleotide variant Pathogenic rs267606778 GRCh38 Chromosome 20, 59301692: 59301692
9 EDN3 NM_207034.2(EDN3): c.277C> G (p.Arg93Gly) single nucleotide variant Pathogenic rs267606779 GRCh37 Chromosome 20, 57876689: 57876689
10 EDN3 NM_207034.2(EDN3): c.277C> G (p.Arg93Gly) single nucleotide variant Pathogenic rs267606779 GRCh38 Chromosome 20, 59301634: 59301634
11 EDN3 NM_207034.2(EDN3): c.293C> A (p.Thr98Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs745795470 GRCh38 Chromosome 20, 59301650: 59301650
12 EDN3 NM_207034.2(EDN3): c.293C> A (p.Thr98Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs745795470 GRCh37 Chromosome 20, 57876705: 57876705
13 EDN3 NM_207032.2(EDN3): c.332G> T (p.Cys111Phe) single nucleotide variant Likely pathogenic GRCh38 Chromosome 20, 59301689: 59301689
14 EDN3 NM_207032.2(EDN3): c.332G> T (p.Cys111Phe) single nucleotide variant Likely pathogenic GRCh37 Chromosome 20, 57876744: 57876744
15 EDN3 NM_207034.2(EDN3): c.334C> A (p.His112Asn) single nucleotide variant Likely pathogenic rs977075341 GRCh37 Chromosome 20, 57876746: 57876746
16 EDN3 NM_207034.2(EDN3): c.334C> A (p.His112Asn) single nucleotide variant Likely pathogenic rs977075341 GRCh38 Chromosome 20, 59301691: 59301691

Expression for Waardenburg Syndrome, Type 4b

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

Pathways for Waardenburg Syndrome, Type 4b

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

# Super pathways Score Top Affiliating Genes
1 11.22 MITF SNAI2
2 11 MITF PAX3
3 10.93 MITF PAX3 SNAI2 SOX10
4 10.88 EDN3 EDNRB
5 10.74 MITF PAX3 SOX10

GO Terms for Waardenburg Syndrome, Type 4b

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

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 regulation of transcription, DNA-templated GO:0006355 9.78 MITF PAX3 SNAI2 SOX10
2 multicellular organism development GO:0007275 9.76 EDN3 MITF PAX3 SNAI2
3 positive regulation of transcription, DNA-templated GO:0045893 9.67 MITF PAX3 SOX10
4 negative regulation of apoptotic process GO:0043066 9.67 EDNRB MITF SNAI2 SOX10
5 negative regulation of canonical Wnt signaling pathway GO:0090090 9.51 SNAI2 SOX10
6 peripheral nervous system development GO:0007422 9.43 EDNRB SOX10
7 vasoconstriction GO:0042310 9.4 EDN3 EDNRB
8 neural crest cell migration GO:0001755 9.33 EDN3 EDNRB SOX10
9 enteric nervous system development GO:0048484 9.32 EDNRB SOX10
10 vein smooth muscle contraction GO:0014826 9.26 EDN3 EDNRB
11 pigmentation GO:0043473 9.13 EDNRB MITF SNAI2
12 melanocyte differentiation GO:0030318 8.92 EDN3 EDNRB MITF SOX10

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

# Name GO ID Score Top Affiliating Genes
1 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 9.56 MITF PAX3 SNAI2 SOX10
2 chromatin binding GO:0003682 9.33 MITF SNAI2 SOX10
3 DNA-binding transcription repressor activity, RNA polymerase II-specific GO:0001227 9.32 MITF SNAI2
4 E-box binding GO:0070888 8.96 MITF SNAI2
5 DNA-binding transcription factor activity GO:0003700 8.92 MITF PAX3 SNAI2 SOX10

Sources for Waardenburg Syndrome, Type 4b

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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