Waardenburg Syndrome, Type 4a disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

MCID: WRD020 MIFTS: 45	Waardenburg Syndrome, Type 4a Categories: Genetic diseases, Rare diseases, Eye diseases, Ear diseases, Skin diseases, Fetal diseases, Neuronal diseases
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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

waardenburg syndrome, type 4a:
Inheritance heterogeneous autosomal recessive inheritance autosomal dominant inheritance

Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Fetal diseases
Anatomical: Eye diseases Ear diseases Skin diseases Neuronal diseases

See all MalaCards categories (disease lists)

External Ids:

OMIM ⁵⁷ 277580

Disease Ontology ¹² DOID:0110953

MedGen ⁴² C1848519

MeSH ⁴⁴ D014849

SNOMED-CT via HPO ⁶⁹ 263681008 258211005 103276001 more

UMLS ⁷³ C1848519

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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).

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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:

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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

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Drugs & Therapeutics for Waardenburg Syndrome, Type 4a

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

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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

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Anatomical Context for Waardenburg Syndrome, Type 4a

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

⁴¹

Skin, Eye

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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 )	Verheij J.B....van Essen A.J.	2006
2	A novel mutation in the endothelin B receptor gene in a patient with Shah-Waardenburg syndrome and Down syndrome. ( 11565556 )	Boardman J.P....Lakhoo K.	2001
3	Mutation of the endothelin-3 gene in the Waardenburg-Hirschsprung disease (Shah-Waardenburg syndrome). ( 8630502 )	Edery P....Lyonnet S.	1996
4	A homozygous mutation in the endothelin-3 gene associated with a combined Waardenburg type 2 and Hirschsprung phenotype (Shah- Waardenburg syndrome). ( 8630503 )	Hofstra R.M.W....Buys C.H.C.M.	1996

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Genes for Waardenburg Syndrome, Type 4a

Genes related to Waardenburg Syndrome, Type 4a (1 elite genes):

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubmedIds
1	EDNRB	Endothelin Receptor Type B	Protein Coding	1354.25	Molecular basis known ⁵⁷ Pathogenic ⁶ Causative variation ⁷⁵ Genetic Tests ²⁹ Novoseek inferred ⁵⁵ GeneCards inferred via : Variants (show sections)	8630502 11484199 19764031 (more) 16237557 9279758 11891690 17999358
2	SOX10	SRY-Box 10	Protein Coding	21.8	Novoseek inferred ⁵⁵ GeneCards inferred via : Novoseek inferred (show sections)	12447940 10876038 20130826 (more) 9462749 16504559 18348274 20206619 11454798 19132125 17999358 16330480 11156606 9760192 9720918 15843399 16494873 16650841 11685702 11734543 10441344 10798354
3	EDN3	Endothelin 3	Protein Coding	20.74	Novoseek inferred ⁵⁵ GeneCards inferred via : Novoseek inferred (show sections)	8630503 11303518 9359047 (more) 9279758 17516928 17999358
4	MITF	Melanogenesis Associated Transcription Factor	Protein Coding	19.54	Novoseek inferred ⁵⁵ GeneCards inferred via : Novoseek inferred (show sections)	17999358
5	RET	Ret Proto-Oncogene	Protein Coding	19.32	Novoseek inferred ⁵⁵ GeneCards inferred via : Novoseek inferred (show sections)	7643365
6	EDNRB-AS1	EDNRB Antisense RNA 1	RNA Gene	8.31	GeneCards inferred via : Variants (show sections)

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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

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Expression for Waardenburg Syndrome, Type 4a

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

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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	Pathways in cancer ³⁷	12.05	EDNRB MITF RET
2	Neural Crest Differentiation ¹	11.27	MITF SOX10
3	Endothelins ¹	10.68	EDN3 EDNRB
4	Melanocyte Development and Pigmentation ⁶⁴	10.24	MITF SOX10

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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

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Sources for Waardenburg Syndrome, Type 4a

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⁷⁶ Wikipedia