MCID: WRD020
MIFTS: 45

Waardenburg Syndrome, Type 4a

Categories: Genetic diseases, Rare diseases, Eye diseases, Ear diseases, Skin diseases, Fetal diseases, Neuronal 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
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 waardenburg syndrome type 4 and waardenburg's syndrome. 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 sensorineural hearing impairment and blue irides

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 30)
# Related Disease Score Top Affiliating Genes
1 waardenburg syndrome type 4 29.5 EDN3 EDNRB MITF SOX10
2 waardenburg's syndrome 28.6 EDN3 EDNRB MITF RET SOX10
3 peripheral demyelinating neuropathy, central dysmyelination, waardenburg syndrome, and hirschsprung disease 12.0
4 waardenburg syndrome, type 4b 11.1
5 waardenburg syndrome, type 4c 11.1
6 abcd syndrome 10.2 EDNRB EDNRB-AS1
7 hirschsprung disease 2 10.2 EDNRB EDNRB-AS1
8 multiple endocrine neoplasia, type iib 10.0 EDNRB RET
9 intestinal disease 9.9 EDNRB RET
10 thyroid carcinoma, familial medullary 9.8 EDNRB RET
11 waardenburg syndrome, type 2a 9.8 EDNRB MITF
12 malignant spindle cell melanoma 9.6 MITF SOX10
13 breast angiosarcoma 9.6 MITF SOX10
14 intestinal pseudo-obstruction 9.6 EDNRB RET SOX10
15 familial renal papillary carcinoma 9.5 MITF RET
16 goldberg-shprintzen syndrome 9.5 EDN3 EDNRB RET
17 neurofibroma 9.5 MITF SOX10
18 thyroid cancer, nonmedullary, 2 9.5 EDNRB RET
19 intestinal obstruction 9.5 EDN3 EDNRB RET
20 central hypoventilation syndrome, congenital 9.4 EDN3 EDNRB RET
21 constipation 9.4 EDN3 EDNRB RET
22 melanoma, uveal 9.4 EDNRB MITF
23 waardenburg syndrome, type 2e 9.3 EDNRB MITF SOX10
24 waardenburg syndrome, type 1 9.0 EDN3 MITF SOX10
25 tietz albinism-deafness syndrome 9.0 EDN3 MITF SOX10
26 dyschromatosis symmetrica hereditaria 9.0 EDN3 MITF SOX10
27 colonic disease 8.9 EDN3 EDNRB RET SOX10
28 megacolon 8.9 EDN3 EDNRB RET SOX10
29 cochlear disease 8.6 EDN3 EDNRB MITF SOX10
30 hirschsprung disease 1 7.9 EDN3 EDNRB MITF RET 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 30)
# Description HPO Frequency HPO Source Accession
1 sensorineural hearing impairment 32 HP:0000407
2 blue irides 32 HP:0000635
3 nystagmus 32 HP:0000639
4 hypopigmented skin patches 32 HP:0001053
5 heterochromia iridis 32 HP:0001100
6 ataxia 32 HP:0001251
7 muscular hypotonia 32 HP:0001252
8 global developmental delay 32 HP:0001263
9 polyneuropathy 32 HP:0001271
10 white forelock 32 hallmark (90%) HP:0002211
11 premature graying of hair 32 hallmark (90%) HP:0002216
12 white eyebrow 32 hallmark (90%) HP:0002226
13 white eyelashes 32 hallmark (90%) HP:0002227
14 aganglionic megacolon 32 hallmark (90%) HP:0002251
15 autonomic dysregulation 32 HP:0002271
16 spastic paraparesis 32 HP:0002313
17 leukodystrophy 32 HP:0002415
18 hearing impairment 32 hallmark (90%) HP:0000365
19 prominent nasal bridge 32 frequent (33%) HP:0000426
20 underdeveloped nasal alae 32 frequent (33%) HP:0000430
21 wide nasal bridge 32 frequent (33%) HP:0000431
22 abnormality of vision 32 hallmark (90%) HP:0000504
23 telecanthus 32 occasional (7.5%) HP:0000506
24 synophrys 32 frequent (33%) HP:0000664
25 abnormal macular morphology 32 hallmark (90%) HP:0001103
26 olfactory lobe agenesis 32 frequent (33%) HP:0001341
27 constipation 32 hallmark (90%) HP:0002019
28 abdominal pain 32 frequent (33%) HP:0002027
29 intestinal obstruction 32 hallmark (90%) HP:0005214
30 abnormality of retinal pigmentation 32 occasional (7.5%) HP:0007703

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

46
# 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 EDNRB MITF RET SOX10 EDN3
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 29 EDNRB

Anatomical Context for Waardenburg Syndrome, Type 4a

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

41
Skin, Eye

Publications for Waardenburg Syndrome, Type 4a

Articles related to Waardenburg Syndrome, Type 4a:

# Title Authors Year
1
Shah-Waardenburg syndrome and PCWH associated with SOX10 mutations: a case report and review of the literature. ( 16504559 )
2006
2
A novel mutation in the endothelin B receptor gene in a patient with Shah-Waardenburg syndrome and Down syndrome. ( 11565556 )
2001
3
Mutation of the endothelin-3 gene in the Waardenburg-Hirschsprung disease (Shah-Waardenburg syndrome). ( 8630502 )
1996
4
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
# Gene Variation Type Significance SNP ID Assembly Location
1 EDNRB NM_000115.4(EDNRB): c.828G> T (p.Trp276Cys) single nucleotide variant Pathogenic,risk factor rs104894387 GRCh37 Chromosome 13, 78475316: 78475316
2 EDNRB NM_000115.4(EDNRB): c.828G> T (p.Trp276Cys) single nucleotide variant Pathogenic,risk factor 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.757C> T (p.Arg253Ter) single nucleotide variant Pathogenic rs104894390 GRCh37 Chromosome 13, 78477335: 78477335
6 EDNRB NM_000115.4(EDNRB): c.757C> T (p.Arg253Ter) single nucleotide variant Pathogenic rs104894390 GRCh38 Chromosome 13, 77903200: 77903200

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 11)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription, DNA-templated GO:0045893 9.67 MITF RET SOX10
2 negative regulation of apoptotic process GO:0043066 9.65 EDNRB MITF RET
3 positive regulation of gene expression GO:0010628 9.63 MITF RET SOX10
4 pigmentation GO:0043473 9.43 EDNRB MITF
5 response to pain GO:0048265 9.4 EDNRB RET
6 vasoconstriction GO:0042310 9.37 EDN3 EDNRB
7 enteric nervous system development GO:0048484 9.32 EDNRB RET
8 vein smooth muscle contraction GO:0014826 9.26 EDN3 EDNRB
9 posterior midgut development GO:0007497 9.16 EDNRB RET
10 neural crest cell migration GO:0001755 9.13 EDN3 EDNRB RET
11 melanocyte differentiation GO:0030318 8.8 EDN3 EDNRB MITF

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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