MCID: WRD030
MIFTS: 52

Waardenburg Syndrome, Type 1

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

Aliases & Classifications for Waardenburg Syndrome, Type 1

MalaCards integrated aliases for Waardenburg Syndrome, Type 1:

Name: Waardenburg Syndrome, Type 1 53 13
Waardenburg Syndrome Type 1 12 72 49 55 28 69
Ws1 53 12 49 55 71
Waardenburg Syndrome Type I 12 23 55
Waardenburg Syndrome with Dystopia Canthorum 53
Waardenburg's Syndrome Type 1 49
Waardenburg Syndrome, Type I 51
Waardenburg Syndrome 1 71

Characteristics:

Orphanet epidemiological data:

55
waardenburg syndrome type 1
Inheritance: Autosomal dominant; Age of onset: Neonatal; Age of death: normal life expectancy;

OMIM:

53
Inheritance:
autosomal dominant

Miscellaneous:
clinical variability seen in waardenburg syndrome type 1
other variants of waardenburg syndrome include waardenburg syndrome type 2 , waardenburg syndrome type 3 , and waardenburg syndrome type 4


HPO:

31
waardenburg syndrome, type 1:
Inheritance autosomal dominant inheritance


GeneReviews:

23
Penetrance Ws1 showed penetrance of at least 85% [preus et al 1983] before the advent of molecular testing. careful examination of individuals identified on the basis of pedigree analysis as having a pax3 pathogenic variant usually reveals subtle findings (minor criteria). hence, those individuals with an affected first-degree relative should be examined closely as the penetrance is likely almost complete...

Classifications:



Summaries for Waardenburg Syndrome, Type 1

UniProtKB/Swiss-Prot : 71 Waardenburg syndrome 1: WS1 is an autosomal dominant disorder characterized by non-progressive sensorineural deafness, pigmentary disturbances such as frontal white blaze of hair, heterochromia of irides, white eyelashes, leukoderma, and wide bridge of nose owing to lateral displacement of the inner canthus of each eye (dystopia canthorum). WS1 shows variable clinical expression and some affected individuals do not manifest hearing impairment or iris pigmentation disturbances. Dystopia canthorum is the most consistent sign and is found in 98% of the patients.

MalaCards based summary : Waardenburg Syndrome, Type 1, also known as waardenburg syndrome type 1, is related to waardenburg syndrome, type 2e and hirschsprung disease 1, and has symptoms including ptosis, scoliosis and mandibular prognathia. An important gene associated with Waardenburg Syndrome, Type 1 is PAX3 (Paired Box 3), and among its related pathways/superpathways are Transcriptional misregulation in cancer and Embryonic and Induced Pluripotent Stem Cell Differentiation Pathways and Lineage-specific Markers. The drugs Warfarin and Ephedrine have been mentioned in the context of this disorder. Affiliated tissues include eye, skin and bone, and related phenotypes are embryo and integument

OMIM : 53 Waardenburg syndrome type 1 is an autosomal dominant auditory-pigmentary syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes; congenital sensorineural hearing loss; and 'dystopia canthorum,' the lateral displacement of the ocular inner canthi (reviews by Read and Newton, 1997, Tamayo et al., 2008, and Pingault et al., 2010). (193500)

NIH Rare Diseases : 49 Waardenburg syndrome type 1 is a genetic condition characterized by eyes that appear widely spaced, congenitalhearing loss, and patchy pigment disturbances of the iris, hair and skin. Mutations in the PAX3 gene cause the symptoms observed in this condition. Treatment is symptomatic and supportive. Waardenburg syndrome type 1 is inherited in an autosomal dominant manner. Last updated: 10/20/2011

Disease Ontology : 12 A Waardenburg's syndrome characterized by autosomal dominant inheritance of congenital deafness, pigmentation anomalies of eyes, hair, and skin,and dystopia canthorum that has material basis in heterozygous mutation in the PAX3 gene on chromosome 2q36.

Wikipedia : 72 Waardenburg syndrome is a rare genetic disorder most often characterized by varying degrees of deafness,... more...

GeneReviews: NBK1531

Related Diseases for Waardenburg Syndrome, Type 1

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 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 36)
# Related Disease Score Top Affiliating Genes
1 waardenburg syndrome, type 2e 31.1 MITF SOX10
2 hirschsprung disease 1 28.2 EDN3 MITF PAX3 SOX10
3 waardenburg syndrome, type 2d 11.0
4 waardenburg syndrome, type 2a 10.8
5 waardenburg syndrome, type 2b 10.8
6 waardenburg syndrome, type 2c 10.8
7 waardenburg syndrome, type 4b 10.8
8 waardenburg syndrome, type 4c 10.8
9 septooptic dysplasia 10.1
10 neural tube defects 10.0
11 childhood kidney cell carcinoma 9.9 MITF PAX3
12 wolfram syndrome 9.9
13 cholesteatoma 9.9
14 piebald trait 9.9 MITF PAX3
15 dilution, pigmentary 9.8
16 heterochromia iridis 9.8
17 ischiocoxopodopatellar syndrome 9.8
18 waardenburg syndrome, type 3 9.8
19 neural tube defects, folate-sensitive 9.8
20 cleft lip 9.8
21 cleft lip/palate 9.8
22 small cell sarcoma 9.8 PAX3 SOX10
23 hermansky-pudlak syndrome 1 9.8 PAX3 SOX10
24 malignant spindle cell melanoma 9.7 MITF SOX10
25 colonic disease 9.7 EDN3 SOX10
26 breast angiosarcoma 9.7 MITF SOX10
27 megacolon 9.6 EDN3 SOX10
28 nonsyndromic deafness 9.6 MITF PAX3
29 inner ear disease 9.6 PAX3 SOX10
30 neurofibroma 9.6 MITF SOX10
31 waardenburg syndrome type 4 9.4 EDN3 MITF SOX10
32 waardenburg syndrome, type 4a 9.3 EDN3 MITF SOX10
33 tietz albinism-deafness syndrome 9.0 EDN3 MITF PAX3 SOX10
34 cochlear disease 9.0 EDN3 MITF PAX3 SOX10
35 dyschromatosis symmetrica hereditaria 9.0 EDN3 MITF PAX3 SOX10
36 waardenburg's syndrome 9.0 EDN3 MITF PAX3 SOX10

Graphical network of the top 20 diseases related to Waardenburg Syndrome, Type 1:



Diseases related to Waardenburg Syndrome, Type 1

Symptoms & Phenotypes for Waardenburg Syndrome, Type 1

Symptoms via clinical synopsis from OMIM:

53
Head And Neck Eyes:
hypertelorism
blepharophimosis
synophrys
laterally displaced inner canthi (dystopia canthorum) (95 to 99%)
increased intercanthal distance
more
Head And Neck Face:
smooth philtrum
decreased philtrum length

Skin Nails Hair Hair:
premature graying of hair
white forelock
bushy eyebrows
white eyelashes and eyebrows

Head And Neck Mouth:
cleft lip/palate
mandibular prognathism

Head And Neck Ears:
congenital sensorineural deafness

Genitourinary Internal Genitalia Female:
absent uterine adnexa (rare)

Neurologic Central Nervous System:
spina bifida (less common)
myelomeningocele (less common)

Head And Neck Nose:
wide nasal bridge
hypoplastic alae nasi
broad, high nasal root
decreased nasal bone length

Skeletal Spine:
sprengel anomaly
supernumerary vertebrae

Chest RibsSternum Clavicles And Scapulae:
supernumerary ribs

Skin Nails Hair Skin:
congenital partial albinism (leukoderma) on face, trunk, or limbs
hypopigmented skin lesions

Genitourinary External Genitalia Female:
absent vagina (rare)

Skeletal Skull:
aplasia of posterior semicircular canal on ct scan


Clinical features from OMIM:

193500

Human phenotypes related to Waardenburg Syndrome, Type 1:

55 31 (show all 44)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ptosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0000508
2 scoliosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0002650
3 mandibular prognathia 55 31 hallmark (90%) Very frequent (99-80%) HP:0000303
4 wide nasal bridge 55 31 frequent (33%) Frequent (79-30%) HP:0000431
5 short nose 55 31 hallmark (90%) Very frequent (99-80%) HP:0003196
6 thick eyebrow 55 31 hallmark (90%) Very frequent (99-80%) HP:0000574
7 abnormality of vision 55 31 hallmark (90%) Very frequent (99-80%) HP:0000504
8 cleft palate 55 31 occasional (7.5%) Occasional (29-5%) HP:0000175
9 strabismus 55 31 occasional (7.5%) Occasional (29-5%) HP:0000486
10 sprengel anomaly 55 31 occasional (7.5%) Occasional (29-5%) HP:0000912
11 hypopigmented skin patches 55 31 hallmark (90%) Very frequent (99-80%) HP:0001053
12 underdeveloped nasal alae 55 31 frequent (33%) Frequent (79-30%) HP:0000430
13 telecanthus 55 31 hallmark (90%) Very frequent (99-80%) HP:0000506
14 heterochromia iridis 55 31 hallmark (90%) Very frequent (99-80%) HP:0001100
15 premature graying of hair 55 31 frequent (33%) Frequent (79-30%) HP:0002216
16 aganglionic megacolon 55 31 occasional (7.5%) Occasional (29-5%) HP:0002251
17 meningocele 55 31 occasional (7.5%) Occasional (29-5%) HP:0002435
18 lacrimation abnormality 55 31 hallmark (90%) Very frequent (99-80%) HP:0000632
19 white forelock 55 31 hallmark (90%) Very frequent (99-80%) HP:0002211
20 tented upper lip vermilion 55 31 frequent (33%) Frequent (79-30%) HP:0010804
21 white hair 55 31 hallmark (90%) Very frequent (99-80%) HP:0011364
22 cleft upper lip 55 31 occasional (7.5%) Occasional (29-5%) HP:0000204
23 synophrys 55 31 frequent (33%) Frequent (79-30%) HP:0000664
24 white eyebrow 55 31 hallmark (90%) Very frequent (99-80%) HP:0002226
25 white eyelashes 55 31 hallmark (90%) Very frequent (99-80%) HP:0002227
26 congenital sensorineural hearing impairment 55 31 hallmark (90%) Very frequent (99-80%) HP:0008527
27 hypertelorism 31 HP:0000316
28 hearing impairment 55 Very frequent (99-80%)
29 smooth philtrum 31 HP:0000319
30 abnormality of the eye 55 Very frequent (99-80%)
31 malformation of the heart and great vessels 55 Occasional (29-5%)
32 hypopigmentation of hair 55 Very frequent (99-80%)
33 spina bifida 55 Occasional (29-5%)
34 blepharophimosis 31 HP:0000581
35 hypopigmentation of the fundus 31 HP:0007894
36 abnormality of the hair 55 Frequent (79-30%)
37 supernumerary ribs 31 HP:0005815
38 oral cleft 31 HP:0000202
39 abnormality of cardiovascular system morphology 31 occasional (7.5%) HP:0030680
40 partial albinism 31 HP:0007443
41 myelomeningocele 31 occasional (7.5%) HP:0002475
42 hypoplastic iris stroma 31 HP:0007990
43 supernumerary vertebrae 31 HP:0002946
44 aplasia of the vagina 31 HP:0003250

MGI Mouse Phenotypes related to Waardenburg Syndrome, Type 1:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 embryo MP:0005380 9.46 EDN3 MITF PAX3 SOX10
2 integument MP:0010771 9.26 EDN3 MITF PAX3 SOX10
3 pigmentation MP:0001186 8.92 EDN3 MITF PAX3 SOX10

Drugs & Therapeutics for Waardenburg Syndrome, Type 1

Drugs for Waardenburg Syndrome, Type 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 20)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Warfarin Approved 81-81-2 54678486 6691
2
Ephedrine Approved 299-42-3 9294
3
Histamine Approved, Investigational 51-45-6, 75614-87-8 774
4
Imipramine Approved 50-49-7 3696
5
Loratadine Approved, Investigational 79794-75-5 3957
6
Pseudoephedrine Approved 90-82-4 7028
7 Anticoagulants
8 Platelet Aggregation Inhibitors
9 Anti-Allergic Agents
10 Antidepressive Agents
11 Antidepressive Agents, Tricyclic
12 Antipruritics
13 Antipsychotic Agents
14 Dermatologic Agents
15 Histamine Antagonists
16 Histamine H1 Antagonists
17 Histamine H1 Antagonists, Non-Sedating
18
Histamine Phosphate 51-74-1 65513
19 Neurotransmitter Agents
20 Quetiapine Fumarate 111974-72-2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Ongoing WARfarin and Coronary STENTing Unknown status NCT00722319
2 Effectiveness of Qufeng Shengshi Fang on Treatment of Allergic Rhinitis. Not yet recruiting NCT02653339 Qufeng Shengshi Fang and Loratadine;Loratadine

Search NIH Clinical Center for Waardenburg Syndrome, Type 1

Genetic Tests for Waardenburg Syndrome, Type 1

Genetic tests related to Waardenburg Syndrome, Type 1:

# Genetic test Affiliating Genes
1 Waardenburg Syndrome Type 1 28 PAX3

Anatomical Context for Waardenburg Syndrome, Type 1

MalaCards organs/tissues related to Waardenburg Syndrome, Type 1:

38
Eye, Skin, Bone, Heart, Testes

Publications for Waardenburg Syndrome, Type 1

Articles related to Waardenburg Syndrome, Type 1:

(show all 12)
# Title Authors Year
1
Novel PAX3 mutations causing Waardenburg syndrome type 1 in Tunisian patients. ( 29224756 )
2017
2
A novel missense mutation of the paired box 3 gene in a Turkish family with Waardenburg syndrome type 1. ( 23378733 )
2013
3
PAX3 mutations and clinical characteristics in Chinese patients with Waardenburg syndrome type 1. ( 20664692 )
2010
4
Waardenburg syndrome type 1. ( 16638435 )
2006
5
[Clinical and molecular genetic investigation of Waardenburg syndrome type 1]. ( 12666593 )
2003
6
Three novel PAX3 mutations observed in patients with Waardenburg syndrome type 1. ( 9067759 )
1997
7
Analysis of locus heterogeneity in Waardenburg syndrome types 1 and 2 using highly informative microsatellite markers. ( 7590754 )
1995
8
Further elucidation of the genomic structure of PAX3, and identification of two different point mutations within the PAX3 homeobox that cause Waardenburg syndrome type 1 in two families. ( 7825605 )
1995
9
A single base pair substitution within the paired box of PAX3 in an individual with Waardenburg syndrome type 1 (WS1). ( 7833953 )
1994
10
A plus-one frameshift mutation in PAX3 alters the entire deduced amino acid sequence of the paired box in a Waardenburg syndrome type 1 (WS1) family. ( 7902163 )
1993
11
Mutations in the PAX3 gene causing Waardenburg syndrome type 1 and type 2. ( 8490648 )
1993
12
A frameshift mutation in the HuP2 paired domain of the probable human homolog of murine Pax-3 is responsible for Waardenburg syndrome type 1 in an Indonesian family. ( 1303193 )
1992

Variations for Waardenburg Syndrome, Type 1

UniProtKB/Swiss-Prot genetic disease variations for Waardenburg Syndrome, Type 1:

71 (show all 23)
# Symbol AA change Variation ID SNP ID
1 PAX3 p.Phe45Leu VAR_003790
2 PAX3 p.Pro50Leu VAR_003793 rs104893650
3 PAX3 p.Arg56Leu VAR_003794 rs267606931
4 PAX3 p.Ile59Phe VAR_003795
5 PAX3 p.Ile59Asn VAR_003796
6 PAX3 p.Val60Met VAR_003797
7 PAX3 p.Met62Val VAR_003798
8 PAX3 p.Gly81Ala VAR_003800 rs587776586
9 PAX3 p.Lys85Glu VAR_003802
10 PAX3 p.Gly99Asp VAR_003803
11 PAX3 p.Phe238Ser VAR_003804
12 PAX3 p.Val265Phe VAR_003805
13 PAX3 p.Arg271Gly VAR_003806
14 PAX3 p.Arg270Cys VAR_013619
15 PAX3 p.Ser73Leu VAR_013640
16 PAX3 p.Gln391His VAR_013641
17 PAX3 p.Gly48Arg VAR_017533
18 PAX3 p.Val78Met VAR_017534
19 PAX3 p.Trp266Cys VAR_017536
20 PAX3 p.Arg271Cys VAR_017537
21 PAX3 p.Arg271His VAR_017538 rs774528745
22 PAX3 p.His80Asp VAR_079619 rs387906947
23 PAX3 p.Leu234Pro VAR_079621

ClinVar genetic disease variations for Waardenburg Syndrome, Type 1:

6 (show all 12)
# Gene Variation Type Significance SNP ID Assembly Location
1 PAX3 NM_181457.3(PAX3): c.238C> G (p.His80Asp) single nucleotide variant Pathogenic rs387906947 GRCh37 Chromosome 2, 223161780: 223161780
2 PAX3 PAX3, 1-BP DEL, 556C deletion Pathogenic
3 PAX3 PAX3, 5-BP DEL, EX5 deletion Pathogenic
4 PAX3 PAX3, 18-BP DEL, EX2 deletion Pathogenic
5 PAX3 NM_181457.3(PAX3): c.149C> T (p.Pro50Leu) single nucleotide variant Pathogenic rs104893650 GRCh37 Chromosome 2, 223161869: 223161869
6 PAX3 PAX3, 14-BP DEL, EX2 deletion Pathogenic
7 PAX3 PAX3, 1-BP DEL deletion Pathogenic
8 PAX3 PAX3, 2-BP DEL, 556CA deletion Pathogenic
9 PAX3 NM_181457.3(PAX3): c.242G> C (p.Gly81Ala) single nucleotide variant Pathogenic rs587776586 GRCh37 Chromosome 2, 223161776: 223161776
10 PAX3 NM_001127366.2(PAX3): c.251C> T (p.Ser84Phe) single nucleotide variant Pathogenic rs104893651 GRCh37 Chromosome 2, 223161767: 223161767
11 PAX3 NM_181457.3(PAX3): c.167G> T (p.Arg56Leu) single nucleotide variant Pathogenic rs267606931 GRCh37 Chromosome 2, 223161851: 223161851
12 PAX3 NM_181459.3(PAX3): c.415A> T (p.Lys139Ter) single nucleotide variant Pathogenic rs876661317 GRCh37 Chromosome 2, 223160283: 223160283

Expression for Waardenburg Syndrome, Type 1

Search GEO for disease gene expression data for Waardenburg Syndrome, Type 1.

Pathways for Waardenburg Syndrome, Type 1

GO Terms for Waardenburg Syndrome, Type 1

Biological processes related to Waardenburg Syndrome, Type 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription, DNA-templated GO:0045893 9.13 MITF PAX3 SOX10
2 melanocyte differentiation GO:0030318 8.62 MITF SOX10

Molecular functions related to Waardenburg Syndrome, Type 1 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 1

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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