Waardenburg Syndrome, Type 4a malady

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

Aliases & Classifications for Waardenburg Syndrome, Type 4a

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11Disease Ontology, 12diseasecard, 13DISEASES, 24GeneTests, 25Genetics Home Reference, 26GTR, 30ICD10 via Orphanet, 36MedGen, 38MeSH, 39MESH via Orphanet, 44NCIt, 47NIH Rare Diseases, 49Novoseek, 51OMIM, 53Orphanet, 61SNOMED-CT, 63The Human Phenotype Ontology, 67UMLS, 68UMLS via Orphanet, 69UniProtKB/Swiss-Prot, 70Wikipedia
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Aliases & Descriptions for Waardenburg Syndrome, Type 4a:

Name: Waardenburg Syndrome, Type 4a 51 12 67
Waardenburg Syndrome 11 70 47 25 53 26 38 67
Waardenburg's Syndrome 11 25 13
Van Der Hoeve Halbertsma Waardenburg Gualdi Syndrome 47 67
Waardenburg Syndrome Type Iva 24 69
Shah-Waardenburg Syndrome 69 49
Waardenburg Syndrome 4a 69 26
Ws4a 24 69
Waardenburg Syndrome with Hirschsprung Disease, Type 4a 24
Waardenburg Syndrome with Hirschsprung Disease Type 4a 69
Van Der Hoeve Halbertsona Waardenburg Syndrome 11
Hirschsprung Disease with Pigmentary Anomaly 69
Waardenburg, Types I and/or Ii 11
Waardenburg-Klein Syndrome 11
Waardenburg Shah Syndrome 11
Waardenburg-Shah Syndrome 69
Waardenburgs Syndrome 49
Klein's Syndrome 67
Mende Syndrome 47


Orphanet epidemiological data:

waardenburg syndrome:
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: 1-9/1000000 (Europe); Age of onset: Infancy,Neonatal; Age of death: normal life expectancy




External Ids:

OMIM51 277580
Disease Ontology11 DOID:9258
MeSH38 D014849
Orphanet53 ORPHA3440
SNOMED-CT61 47434006
ICD10 via Orphanet30 E70.3
UMLS via Orphanet68 C0043008
MESH via Orphanet39 D014849
MedGen36 C1848519

Summaries for Waardenburg Syndrome, Type 4a

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OMIM:51 Waardenburg syndrome type 4 (WS4), also known as Waardenburg-Shah syndrome, is an auditory-pigmentary syndrome... (277580) more...

MalaCards based summary: Waardenburg Syndrome, Type 4a, also known as waardenburg syndrome, is related to hirschsprung disease 1 and waardenburg syndrome, type 1, and has symptoms including conductive hearing impairment, prominent nasal bridge and synophrys. An important gene associated with Waardenburg Syndrome, Type 4a is EDNRB (Endothelin Receptor Type B), and among its related pathways are Melanocyte Development and Pigmentation and Embryonic and Induced Pluripotent Stem Cell Differentiation Pathways and Lineage-specific Markers. Affiliated tissues include skin, eye and uterus, and related mouse phenotypes are hearing/vestibular/ear and muscle.

Disease Ontology:11 An autosomal disease characterized by varying degrees of deafness, minor defects in structures arising from the neural crest and pigmentation anomalies of the hair, the skin and/or the iris of both eyes.

Genetics Home Reference:25 Waardenburg syndrome is a group of genetic conditions that can cause hearing loss and changes in coloring (pigmentation) of the hair, skin, and eyes. Although most people with Waardenburg syndrome have normal hearing, moderate to profound hearing loss can occur in one or both ears. The hearing loss is present from birth (congenital). People with this condition often have very pale blue eyes or different colored eyes, such as one blue eye and one brown eye. Sometimes one eye has segments of two different colors. Distinctive hair coloring (such as a patch of white hair or hair that prematurely turns gray) is another common sign of the condition. The features of Waardenburg syndrome vary among affected individuals, even among people in the same family.

UniProtKB/Swiss-Prot:69 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).

Wikipedia:70 Waardenburg syndrome is a rare genetic disorder most often characterized by varying degrees of deafness,... more...

Related Diseases for Waardenburg Syndrome, Type 4a

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Diseases in the Waardenburg Syndrome, Type 4a family:

Waardenburg Syndrome, Type 2b Waardenburg Syndrome, Type 1
Waardenburg Syndrome, Type 3 Waardenburg Syndrome, Type 2a
Waardenburg Syndrome, Type 2c Waardenburg Syndrome, Type 2d
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 43)
idRelated DiseaseScoreTop Affiliating Genes
1hirschsprung disease 132.3EDN3, EDNRB, RET
2waardenburg syndrome, type 131.7ALPP, EDN3, MITF, PAX3, SOX10
3mend syndrome12.2
4pcwh syndrome11.8
5waardenburg syndrome, type 311.1
6waardenburg syndrome, type 2a11.1
7waardenburg syndrome, type 4b11.0
8waardenburg syndrome, type 4c11.0
9waardenburg syndrome type 411.0
10waardenburg syndrome/ocular albinism, digenic10.6MITF, TYR
11pyloric stenosis, infantile hypertrophic, 310.6MITF, TYR
12albinism, oculocutaneous, type ib10.6MITF, TYR
13melanoma, cutaneous malignant 810.5MITF, TYR
14placental insufficiency10.5EDNRB, RET, SOX10
15charcot-marie-tooth neuropathy, x-linked recessive, 210.5MITF, SNAI2, SOX10
16anal margin carcinoma10.5MITF, TYR
17stomach diverticulosis10.5MITF, TYR
18nonsyndromic congenital nail disorder 210.5EDN3, EDNRB, RET
19agammaglobulinemia 410.5PAX3, SOX10, TYR
20shprintzen-goldberg syndrome10.5EDN3, EDNRB, RET
21dentinogenesis imperfecta, shields type ii10.4MITF, PAX3, SNAI2
22postgastrectomy syndrome10.4EDN3, EDNRB, RET
23autism susceptibility 1610.4MITF, TYR, TYRP1
24hyperglycemia10.4GJB2, MITF
25hirschsprung nail hypoplasia dysmorphism10.4EDN3, EDNRB, MITF, SOX10
26central hypoventilation syndrome, congenital10.4EDNRB, RET
27pulmonary coin lesion10.3EDN3, EDNRB, RET, SOX10
28nail disorder, nonsyndromic congenital, 710.3MITF, TYR, TYRP1
29gnathomiasis10.3EDN3, EDNRB, RET, SOX10
30y-linked disease10.3GJB2, PAX3, RET
31craniofacial-deafness-hand syndrome10.3KIR2DS4, PAX3
32sclerosing hepatic carcinoma10.3PAX3, PAX7
33diabetes mellitus, noninsulin-dependent, 510.2EDN3, EDNRB, MITF, RET, SOX10
34necrotizing ulcerative gingivitis10.2PAX6, RET
35prostate rhabdomyosarcoma10.1PAX3, PAX7
36heterochromia iridis10.0
37conjunctival cancer10.0EDN3, EDNRB, MITF, PAX3, SNAI2, SOX10
38chronic infections, due to mbl deficiency10.0EDN3, EDNRB, MITF, PAX3, RET, SOX10
39partial optic atrophy10.0MITF, PAX6, TYR, TYRP1
40dyschromatosis symmetrica hereditaria9.9EDN3, MITF, PAX3, SOX10, TYR, TYRP1
41glaucoma 3a, primary open angle, congenital, juvenile, or adult onset9.9PAX6, TYR
42hypogonadotropic hypogonadism 24 without anosmia9.8KIR2DS4, PAX3, PAX6, TYR
43neural tube defects9.7PAX1, PAX3, PAX7, SNAI2

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

Diseases related to waardenburg syndrome, type 4a

Symptoms for Waardenburg Syndrome, Type 4a

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Symptoms by clinical synopsis from OMIM:


Clinical features from OMIM:


Human phenotypes related to Waardenburg Syndrome, Type 4a:

 63 53 (show all 42)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 conductive hearing impairment63 53 hallmark (90%) Very frequent (99-80%) HP:0000405
2 prominent nasal bridge63 53 hallmark (90%) Very frequent (99-80%) HP:0000426
3 synophrys63 53 hallmark (90%) Very frequent (99-80%) HP:0000664
4 hypopigmented skin patches63 53 hallmark (90%) Very frequent (99-80%) HP:0001053
5 heterochromia iridis63 53 hallmark (90%) Very frequent (99-80%) HP:0001100
6 abnormal facial shape63 53 hallmark (90%) Very frequent (99-80%) HP:0001999
7 premature graying of hair63 53 hallmark (90%) Very frequent (99-80%) HP:0002216
8 underdeveloped nasal alae63 53 typical (50%) Frequent (79-30%) HP:0000430
9 wide nasal bridge63 53 typical (50%) Frequent (79-30%) HP:0000431
10 telecanthus63 53 typical (50%) Frequent (79-30%) HP:0000506
11 lacrimation abnormality63 53 typical (50%) Frequent (79-30%) HP:0000632
12 white forelock63 53 typical (50%) Frequent (79-30%) HP:0002211
13 abnormality of the vagina63 53 occasional (7.5%) Occasional (29-5%) HP:0000142
14 oral cleft63 53 occasional (7.5%) Occasional (29-5%) HP:0000202
15 ptosis63 53 occasional (7.5%) Occasional (29-5%) HP:0000508
16 aganglionic megacolon63 53 occasional (7.5%) Occasional (29-5%) HP:0002251
17 myelomeningocele63 53 occasional (7.5%) Occasional (29-5%) HP:0002475
18 intestinal obstruction63 53 occasional (7.5%) Occasional (29-5%) HP:0005214
19 aplasia/hypoplasia of the colon63 53 occasional (7.5%) Occasional (29-5%) HP:0100811
20 sensorineural hearing impairment63 HP:0000407
21 blue irides63 HP:0000635
22 nystagmus63 HP:0000639
23 ataxia63 HP:0001251
24 muscular hypotonia63 HP:0001252
25 global developmental delay63 HP:0001263
26 polyneuropathy63 HP:0001271
27 white eyebrow63 HP:0002226
28 white eyelashes63 HP:0002227
29 autonomic dysregulation63 HP:0002271
30 spastic paraparesis63 HP:0002313
31 leukodystrophy63 HP:0002415
32 abnormality of the uterus53 Occasional (29-5%)
33 abnormality of the mouth53 Frequent (79-30%)
34 abnormality of the lip53 Frequent (79-30%)
35 abnormality of the face53 Frequent (79-30%)
36 hearing impairment53 Very frequent (99-80%)
37 abnormality of the eye53 Frequent (79-30%)
38 abnormality of vision53 Very frequent (99-80%)
39 abnormality of the eyebrow53 Frequent (79-30%)
40 abnormality of skin pigmentation53 Very frequent (99-80%)
41 hypopigmentation of hair53 Very frequent (99-80%)
42 abnormality of the gastrointestinal tract53 Occasional (29-5%)

UMLS symptoms related to Waardenburg Syndrome, Type 4a:

achromia of skin

Drugs & Therapeutics for Waardenburg Syndrome, Type 4a

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Interventional clinical trials:

idNameStatusNCT IDPhase
1Development and Clinical Application of Two New Genetic Deafness Gene Diagnostic KitRecruitingNCT02418936

Search NIH Clinical Center for Waardenburg Syndrome, Type 4a

Cochrane evidence based reviews: waardenburg syndrome

Genetic Tests for Waardenburg Syndrome, Type 4a

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Genetic tests related to Waardenburg Syndrome, Type 4a:

id Genetic test Affiliating Genes
1 Waardenburg Syndrome Type 4a26
2 Waardenburg Syndrome26
3 Waardenburg Syndrome Type Iva24 EDNRB

Anatomical Context for Waardenburg Syndrome, Type 4a

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

Skin, Eye, Uterus, Colon

Animal Models for Waardenburg Syndrome, Type 4a or affiliated genes

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

40 (show all 22)
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053779.5EDNRB, GJB2, MITF, PAX3, PAX6, TYRP1
2MP:00053698.7EDNRB, FN1, PAX1, PAX3, PAX6, PAX7
3MP:00020068.4EDNRB, FN1, PAX3, PAX6, PAX7, RET
4MP:00053898.3FN1, GJB2, MITF, PAX1, PAX6, RET
5MP:00053798.2EDNRB, MITF, PAX1, PAX3, PAX6, PAX7
6MP:00053718.0AEBP2, EDNRB, FN1, GJB2, MITF, PAX1
7MP:00053827.8EDNRB, FN1, GJB2, MITF, PAX1, PAX3
8MP:00053847.8EDNRB, FN1, GJB2, MITF, PAX1, PAX3
9MP:00053857.7EDNRB, FN1, GJB2, PAX1, PAX3, PAX6
10MP:00053817.7AEBP2, EDN3, EDNRB, PAX3, PAX6, PAX7
11MP:00053877.6EDNRB, FN1, GJB2, MITF, PAX1, PAX3
12MP:00053917.4EDNRB, GJB2, MITF, PAX3, PAX6, PAX7
13MP:00053807.2EBP, EDN3, EDNRB, FN1, GJB2, MITF
14MP:00028737.0FN1, GJB2, MITF, PAX1, PAX3, PAX6
15MP:00011866.9AEBP2, EDN3, EDNRB, MITF, PAX1, PAX3
16MP:00053906.9EDNRB, FN1, GJB2, MITF, PAX1, PAX3
17MP:00053766.8EDNRB, FN1, GJB2, MITF, PAX3, PAX6
18MP:00053866.8AEBP2, EDN3, EDNRB, MITF, PAX1, PAX3
19MP:00036316.7EDN3, EDNRB, FN1, GJB2, MITF, PAX1
20MP:00053786.2AEBP2, EBP, EDNRB, FN1, GJB2, MITF
21MP:00107686.0AEBP2, EBP, EDN3, EDNRB, FN1, GJB2
22MP:00107716.0AEBP2, EBP, EDN3, EDNRB, FN1, GJB2

Publications for Waardenburg Syndrome, Type 4a

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Variations for Waardenburg Syndrome, Type 4a

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

id Symbol AA change Variation ID SNP ID

Clinvar genetic disease variations for Waardenburg Syndrome, Type 4a:

5 (show all 13)
id Gene Variation Type Significance SNP ID Assembly Location
1EBPNM_006579.2(EBP): c.141G> T (p.Trp47Cys)SNVPathogenicrs587783599GRCh37Chr X, 48382300: 48382300
2EDNRBNM_000115.4(EDNRB): c.828G> T (p.Trp276Cys)SNVPathogenic, risk factorrs104894387GRCh37Chr 13, 78475316: 78475316
3EDNRBNM_000115.4(EDNRB): c.548C> G (p.Ala183Gly)SNVPathogenicrs104894388GRCh37Chr 13, 78477678: 78477678
4EDNRBNM_000115.4(EDNRB): c.757C> T (p.Arg253Ter)SNVPathogenicrs104894390GRCh37Chr 13, 78477335: 78477335
5EDNRBNM_000115.4(EDNRB): c.618G> A (p.Trp206Ter)SNVPathogenicrs876657688GRCh38Chr 13, 77903339: 77903339
6MITFNM_198159.2(MITF): c.(?_355)-1203_*(78_?)deldeletionPathogenicGRCh38Chr 3, 69936619: 69965326
7MITFNM_198159.2(MITF): c.(?_938)-102_*(78_?)deldeletionPathogenicGRCh38Chr 3, 69956353: 69965326
8MITFNM_000248.3(MITF): c.722G> A (p.Trp241Ter)SNVPathogenicrs876657698GRCh37Chr 3, 70008435: 70008435
9MITFNM_000248.3(MITF): c.808C> T (p.Arg270Ter)SNVPathogenicrs876657699GRCh37Chr 3, 70008521: 70008521
10MITFNM_000248.3(MITF): c.383C> G (p.Ser128Ter)SNVPathogenicrs876657700GRCh38Chr 3, 69941273: 69941273
11PAX3NM_001127366.2(PAX3): c.(?_-77)_(583_?)+547deldeletionPathogenicGRCh37Chr 2, 223158339: 223163411
12PAX3NM_181457.3(PAX3): c.668G> A (p.Arg223Gln)SNVPathogenicrs876657717GRCh38Chr 2, 222232202: 222232202
13SOX10NM_006941.3(SOX10): c.(?_698)_(1401_?)del (p.(?))deletionPathogenicGRCh37Chr 22, 38369502: 38370205

Expression for genes affiliated with Waardenburg Syndrome, Type 4a

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

Pathways for genes affiliated with Waardenburg Syndrome, Type 4a

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GO Terms for genes affiliated with Waardenburg Syndrome, Type 4a

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Cellular components related to Waardenburg Syndrome, Type 4a according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1melanosome membraneGO:003316210.0TYR, TYRP1

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

(show all 17)
idNameGO IDScoreTop Affiliating Genes
1vein smooth muscle contractionGO:001482610.9EDN3, EDNRB
2posterior midgut developmentGO:000749710.8EDNRB, RET
3vasoconstrictionGO:004231010.7EDN3, EDNRB
4lacrimal gland developmentGO:003280810.6PAX6, SOX10
5response to painGO:004826510.6EDNRB, RET
6enteric nervous system developmentGO:004848410.6EDNRB, RET, SOX10
7melanin biosynthetic processGO:004243810.4TYR, TYRP1
8neural crest cell migrationGO:000175510.2EDN3, EDNRB, RET, SOX10
9melanocyte differentiationGO:003031810.0EDN3, EDNRB, MITF, SOX10, TYRP1
10positive regulation of neuroblast proliferationGO:00020529.9PAX6, SOX10
11pigmentationGO:00434739.5EDNRB, SNAI2, TYR, TYRP1
12transcription from RNA polymerase II promoterGO:00063669.5MITF, PAX1, PAX3, PAX6, SOX10
13positive regulation of gene expressionGO:00106289.5FN1, MITF, PAX6, RET
14negative regulation of apoptotic processGO:00430669.4EDNRB, FN1, PAX7, SNAI2, SOX10
15positive regulation of transcription, DNA-templatedGO:00458939.2MITF, PAX3, PAX6, RET, SOX10, SRY
16positive regulation of transcription from RNA polymerase II promoterGO:00459448.7MITF, PAX1, PAX3, PAX6, PAX7, SOX10
17negative regulation of transcription from RNA polymerase II promoterGO:00001228.2AEBP2, EDNRB, MITF, PAX6, SNAI2, SRY

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

idNameGO IDScoreTop Affiliating Genes
1HMG box domain bindingGO:007183710.1PAX3, PAX6
2transcription factor activity, RNA polymerase II distal enhancer sequence-specific bindingGO:000370510.1SNAI2, SOX10, SRY
3transcription factor activity, sequence-specific DNA bindingGO:00037008.1PAX1, PAX3, PAX6, PAX7, SOX10, TFEC

Sources for Waardenburg Syndrome, Type 4a

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30ICD10 via Orphanet
39MESH via Orphanet
52OMIM via Orphanet
62SNOMED-CT via Orphanet
66Tumor Gene Family of Databases
68UMLS via Orphanet