MCID: WRD020
MIFTS: 46

Waardenburg Syndrome, Type 4a

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

Aliases & Classifications for Waardenburg Syndrome, Type 4a

MalaCards integrated aliases for Waardenburg Syndrome, Type 4a:

Name: Waardenburg Syndrome, Type 4a 53 13 69
Shah-Waardenburg Syndrome 53 71 51
Ws4a 53 12 71
Waardenburg Syndrome with Hirschsprung Disease Type 4a 12 71
Waardenburg Syndrome Type Iva 12 71
Waardenburg Syndrome Type 4a 12 28
Waardenburg-Shah Syndrome 53 71
Waardenburg Syndrome with Hirschsprung Disease, Type 4a 53
Hirschsprung Disease with Pigmentary Anomaly 71
Waardenburg Syndrome, Type Iva 53
Waardenburg Syndrome 4a 71
Ws4 53

Characteristics:

OMIM:

53
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:

31

Classifications:



Summaries for Waardenburg Syndrome, Type 4a

OMIM : 53 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 shah-waardenburg syndrome, is related to waardenburg syndrome type 4 and waardenburg's syndrome, and has symptoms including ataxia, constipation and abdominal pain. 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 behavior/neurological and embryo

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 : 71 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 26)
# Related Disease Score Top Affiliating Genes
1 waardenburg syndrome type 4 30.3 EDN3 EDNRB MITF SOX10
2 waardenburg's syndrome 29.7 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 multiple endocrine neoplasia, type iib 10.0 EDNRB RET
7 constipation 9.9 EDNRB RET
8 intestinal disease 9.8 EDNRB RET
9 malignant spindle cell melanoma 9.8 MITF SOX10
10 breast angiosarcoma 9.7 MITF SOX10
11 lentigines 9.7 EDNRB MITF
12 familial renal papillary carcinoma 9.7 MITF RET
13 intestinal pseudo-obstruction 9.7 EDNRB RET SOX10
14 neurofibroma 9.6 MITF SOX10
15 thyroid carcinoma, familial medullary 9.6 EDNRB RET
16 goldberg-shprintzen syndrome 9.6 EDN3 EDNRB RET
17 intestinal obstruction 9.6 EDN3 EDNRB RET
18 central hypoventilation syndrome, congenital 9.6 EDN3 EDNRB RET
19 waardenburg syndrome, type 2e 9.5 EDNRB MITF SOX10
20 waardenburg syndrome, type 1 9.4 EDN3 MITF SOX10
21 tietz albinism-deafness syndrome 9.3 EDN3 MITF SOX10
22 dyschromatosis symmetrica hereditaria 9.3 EDN3 MITF SOX10
23 colonic disease 9.3 EDN3 EDNRB RET SOX10
24 megacolon 9.3 EDN3 EDNRB RET SOX10
25 cochlear disease 9.0 EDN3 EDNRB MITF SOX10
26 hirschsprung disease 1 8.6 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:

53
SkinNailsHairSkin:
hypopigmented skin patches

SkinNailsHairHair:
white forelock
white eyelashes
white eyebrows
premature graying

AbdomenGastrointestinal:
hirschsprung disease
decreased myenteric and submucosal ganglia in the bowel

HeadAndNeckEyes:
heterochromia iridis
bright blue irides
bicolored irides

HeadAndNeckEars:
deafness, sensorineural


Clinical features from OMIM:

277580

Human phenotypes related to Waardenburg Syndrome, Type 4a:

31 (show all 30)
# Description HPO Frequency HPO Source Accession
1 ataxia 31 HP:0001251
2 constipation 31 hallmark (90%) HP:0002019
3 abdominal pain 31 frequent (33%) HP:0002027
4 nystagmus 31 HP:0000639
5 muscular hypotonia 31 HP:0001252
6 hearing impairment 31 hallmark (90%) HP:0000365
7 global developmental delay 31 HP:0001263
8 wide nasal bridge 31 frequent (33%) HP:0000431
9 sensorineural hearing impairment 31 HP:0000407
10 abnormality of retinal pigmentation 31 occasional (7.5%) HP:0007703
11 abnormality of vision 31 hallmark (90%) HP:0000504
12 hypopigmented skin patches 31 HP:0001053
13 intestinal obstruction 31 hallmark (90%) HP:0005214
14 prominent nasal bridge 31 frequent (33%) HP:0000426
15 underdeveloped nasal alae 31 frequent (33%) HP:0000430
16 telecanthus 31 occasional (7.5%) HP:0000506
17 heterochromia iridis 31 HP:0001100
18 premature graying of hair 31 hallmark (90%) HP:0002216
19 aganglionic megacolon 31 hallmark (90%) HP:0002251
20 blue irides 31 HP:0000635
21 white forelock 31 hallmark (90%) HP:0002211
22 synophrys 31 frequent (33%) HP:0000664
23 white eyebrow 31 hallmark (90%) HP:0002226
24 white eyelashes 31 hallmark (90%) HP:0002227
25 polyneuropathy 31 HP:0001271
26 leukodystrophy 31 HP:0002415
27 spastic paraparesis 31 HP:0002313
28 autonomic dysregulation 31 HP:0002271
29 olfactory lobe agenesis 31 frequent (33%) HP:0001341
30 abnormal macular morphology 31 hallmark (90%) HP:0001103

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

43
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.85 RET SOX10 EDN3 EDNRB MITF
2 embryo MP:0005380 9.8 EDN3 EDNRB MITF RET SOX10
3 digestive/alimentary MP:0005381 9.73 EDN3 EDNRB RET SOX10
4 endocrine/exocrine gland MP:0005379 9.67 EDNRB MITF RET SOX10
5 integument MP:0010771 9.62 EDN3 EDNRB MITF SOX10
6 limbs/digits/tail MP:0005371 9.56 EDNRB MITF RET SOX10
7 mortality/aging MP:0010768 9.55 EDN3 EDNRB MITF RET SOX10
8 nervous system MP:0003631 9.35 EDN3 EDNRB MITF RET SOX10
9 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 28 EDNRB

Anatomical Context for Waardenburg Syndrome, Type 4a

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

38
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
A homozygous mutation in the endothelin-3 gene associated with a combined Waardenburg type 2 and Hirschsprung phenotype (Shah- Waardenburg syndrome). ( 8630503 )
1996
4
Mutation of the endothelin-3 gene in the Waardenburg-Hirschsprung disease (Shah-Waardenburg syndrome). ( 8630502 )
1996

Variations for Waardenburg Syndrome, Type 4a

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

71
# 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.548C> G (p.Ala183Gly) single nucleotide variant Pathogenic rs104894388 GRCh37 Chromosome 13, 78477678: 78477678
3 EDNRB NM_000115.4(EDNRB): c.757C> T (p.Arg253Ter) single nucleotide variant Pathogenic rs104894390 GRCh37 Chromosome 13, 78477335: 78477335

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 12)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription, DNA-templated GO:0045893 9.69 MITF RET SOX10
2 negative regulation of apoptotic process GO:0043066 9.67 EDNRB MITF SOX10
3 positive regulation of gene expression GO:0010628 9.65 MITF RET SOX10
4 pigmentation GO:0043473 9.46 EDNRB MITF
5 peripheral nervous system development GO:0007422 9.43 EDNRB SOX10
6 response to pain GO:0048265 9.4 EDNRB RET
7 vasoconstriction GO:0042310 9.37 EDN3 EDNRB
8 neural crest cell migration GO:0001755 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 melanocyte differentiation GO:0030318 9.13 EDNRB MITF SOX10
12 enteric nervous system development GO:0048484 8.8 EDNRB RET 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 8.62 MITF SOX10

Sources for Waardenburg Syndrome, Type 4a

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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