MCID: WRD030
MIFTS: 52

Waardenburg Syndrome, Type 1

Categories: Genetic diseases, Rare diseases, Eye diseases, Ear 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 54 13
Waardenburg Syndrome Type 1 12 50 56 29 69
Waardenburg Syndrome Type I 12 23 24 56
Ws1 12 50 56 71
Waardenburg's Syndrome Type 1 50
Waardenburg Syndrome, Type I 52
Waardenburg Syndrome 1 71

Characteristics:

Orphanet epidemiological data:

56
waardenburg syndrome type 1
Inheritance: Autosomal dominant; Age of onset: Neonatal; Age of death: normal life expectancy;

OMIM:

54
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:

32
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 2d and waardenburg syndrome, type 2e, with or without neurologic involvement, and has symptoms including scoliosis, strabismus and ptosis. 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 testes, and related phenotypes are embryo and integument

NIH Rare Diseases : 50 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

OMIM : 54
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)

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.

GeneReviews: NBK1531

Related Diseases for Waardenburg Syndrome, Type 1

Diseases in the Waardenburg's Syndrome 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 4a 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 33)
id Related Disease Score Top Affiliating Genes
1 waardenburg syndrome, type 2d 10.9
2 waardenburg syndrome, type 2e, with or without neurologic involvement 10.9
3 waardenburg syndrome, type 2b 10.7
4 waardenburg syndrome, type 2a 10.7
5 waardenburg syndrome, type 2c 10.7
6 waardenburg syndrome, type 4b 10.7
7 waardenburg syndrome, type 4c 10.7
8 multilocular clear cell renal cell carcinoma 10.0 MITF PAX3
9 periventricular nodular heterotopia 3 9.8 MITF PAX3
10 wolfram syndrome 9.8
11 cholesteatoma 9.8
12 ascaridiasis 9.8 PAX3 SOX10
13 autosomal recessive nonsyndromic deafness 9.8 MITF PAX3
14 neural tube defects 9.8
15 cleft lip 9.8
16 heterochromia iridis 9.8
17 cleft lip/palate 9.8
18 agammaglobulinemia 4 9.7 PAX3 SOX10
19 deafness, mitochondrial, modifier of 9.7 MITF SOX10
20 fallopian tube serous papilloma 9.6 MITF SOX10
21 thyroid angiosarcoma 9.6 MITF SOX10
22 wolffian duct adenocarcinoma 9.6 EDN3 SOX10
23 spinal meningioma 9.5 EDN3 SOX10
24 mixed lacrimal gland cancer 9.5 PAX3 SOX10
25 deafness, autosomal recessive 4, with enlarged vestibular aqueduct 9.5 MITF PAX3
26 wallerian degeneration 9.2 EDN3 MITF SOX10
27 diabetes mellitus, noninsulin-dependent, 5 9.2 EDN3 MITF SOX10
28 melanoma, cutaneous malignant 8 8.8 EDN3 MITF PAX3 SOX10
29 biliary papillomatosis 8.7 EDN3 MITF PAX3 SOX10
30 dyschromatosis symmetrica hereditaria 8.7 EDN3 MITF PAX3 SOX10
31 tyrosinemia 8.7 EDN3 MITF PAX3 SOX10
32 myasthenic syndrome, congenital, 21, presynaptic 8.7 EDN3 MITF PAX3 SOX10
33 waardenburg syndrome, type 3 8.2 ALPP 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:

54

Head And Neck- Eyes:
hypertelorism
synophrys
blepharophimosis
laterally displaced inner canthi (dystopia canthorum) (95 to 99%)
increased intercanthal distance
more
Head And Neck- Nose:
wide nasal bridge
hypoplastic alae nasi
broad, high nasal root
decreased nasal bone length

Head And Neck- Mouth:
cleft lip/palate
mandibular prognathism

Chest- Ribs Sternum Clavicles And Scapulae:
supernumerary ribs

Genitourinary- Internal Genitalia Female:
absent uterine adnexa (rare)

Skeletal- Spine:
sprengel anomaly
supernumerary vertebrae

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

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

Head And Neck- Face:
smooth philtrum
decreased philtrum length

Head And Neck- Ears:
congenital sensorineural deafness

Genitourinary- External Genitalia Female:
absent vagina (rare)

Skeletal- Skull:
aplasia of posterior semicircular canal on ct scan

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


Clinical features from OMIM:

193500

Human phenotypes related to Waardenburg Syndrome, Type 1:

56 32 (show all 44)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 scoliosis 56 32 occasional (7.5%) Occasional (29-5%) HP:0002650
2 strabismus 56 32 occasional (7.5%) Occasional (29-5%) HP:0000486
3 ptosis 56 32 occasional (7.5%) Occasional (29-5%) HP:0000508
4 cleft palate 56 32 occasional (7.5%) Occasional (29-5%) HP:0000175
5 short nose 56 32 hallmark (90%) Very frequent (99-80%) HP:0003196
6 telecanthus 56 32 hallmark (90%) Very frequent (99-80%) HP:0000506
7 white forelock 56 32 hallmark (90%) Very frequent (99-80%) HP:0002211
8 wide nasal bridge 56 32 frequent (33%) Frequent (79-30%) HP:0000431
9 synophrys 56 32 frequent (33%) Frequent (79-30%) HP:0000664
10 sprengel anomaly 56 32 occasional (7.5%) Occasional (29-5%) HP:0000912
11 premature graying of hair 56 32 frequent (33%) Frequent (79-30%) HP:0002216
12 hypopigmented skin patches 56 32 hallmark (90%) Very frequent (99-80%) HP:0001053
13 heterochromia iridis 56 32 hallmark (90%) Very frequent (99-80%) HP:0001100
14 white eyelashes 56 32 hallmark (90%) Very frequent (99-80%) HP:0002227
15 aganglionic megacolon 56 32 occasional (7.5%) Occasional (29-5%) HP:0002251
16 meningocele 56 32 occasional (7.5%) Occasional (29-5%) HP:0002435
17 white hair 56 32 hallmark (90%) Very frequent (99-80%) HP:0011364
18 mandibular prognathia 56 32 hallmark (90%) Very frequent (99-80%) HP:0000303
19 thick eyebrow 56 32 hallmark (90%) Very frequent (99-80%) HP:0000574
20 abnormality of vision 56 32 hallmark (90%) Very frequent (99-80%) HP:0000504
21 underdeveloped nasal alae 56 32 frequent (33%) Frequent (79-30%) HP:0000430
22 lacrimation abnormality 56 32 hallmark (90%) Very frequent (99-80%) HP:0000632
23 tented upper lip vermilion 56 32 frequent (33%) Frequent (79-30%) HP:0010804
24 cleft upper lip 56 32 occasional (7.5%) Occasional (29-5%) HP:0000204
25 white eyebrow 56 32 hallmark (90%) Very frequent (99-80%) HP:0002226
26 congenital sensorineural hearing impairment 56 32 hallmark (90%) Very frequent (99-80%) HP:0008527
27 hypertelorism 32 HP:0000316
28 spina bifida 56 Occasional (29-5%)
29 smooth philtrum 32 HP:0000319
30 blepharophimosis 32 HP:0000581
31 supernumerary ribs 32 HP:0005815
32 supernumerary vertebrae 32 HP:0002946
33 hypoplastic iris stroma 32 HP:0007990
34 hearing impairment 56 Very frequent (99-80%)
35 hypopigmentation of the fundus 32 HP:0007894
36 myelomeningocele 32 occasional (7.5%) HP:0002475
37 oral cleft 32 HP:0000202
38 abnormality of the eye 56 Very frequent (99-80%)
39 malformation of the heart and great vessels 56 Occasional (29-5%)
40 hypopigmentation of hair 56 Very frequent (99-80%)
41 abnormality of the hair 56 Frequent (79-30%)
42 abnormality of cardiovascular system morphology 32 occasional (7.5%) HP:0030680
43 partial albinism 32 HP:0007443
44 aplasia of the vagina 32 HP:0003250

MGI Mouse Phenotypes related to Waardenburg Syndrome, Type 1:

44
id 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)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Warfarin Approved 81-81-2 6691 54678486
2
Ephedrine Approved 299-42-3 9294
3
Histamine Approved, Investigational 75614-87-8, 51-45-6 774
4
Imipramine Approved 50-49-7 3696
5
Loratadine Approved 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:


id 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:

id Genetic test Affiliating Genes
1 Waardenburg Syndrome Type 1 29
2 Waardenburg Syndrome Type I 24 PAX3

Anatomical Context for Waardenburg Syndrome, Type 1

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

39
Eye, Skin, Testes, Bone, Heart

Publications for Waardenburg Syndrome, Type 1

Articles related to Waardenburg Syndrome, Type 1:

(show all 11)
id Title Authors Year
1
A novel missense mutation of the paired box 3 gene in a Turkish family with Waardenburg syndrome type 1. ( 23378733 )
2013
2
PAX3 mutations and clinical characteristics in Chinese patients with Waardenburg syndrome type 1. ( 20664692 )
2010
3
Waardenburg syndrome type 1. ( 16638435 )
2006
4
[Clinical and molecular genetic investigation of Waardenburg syndrome type 1]. ( 12666593 )
2003
5
Three novel PAX3 mutations observed in patients with Waardenburg syndrome type 1. ( 9067759 )
1997
6
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
7
Analysis of locus heterogeneity in Waardenburg syndrome types 1 and 2 using highly informative microsatellite markers. ( 7590754 )
1995
8
A single base pair substitution within the paired box of PAX3 in an individual with Waardenburg syndrome type 1 (WS1). ( 7833953 )
1994
9
Mutations in the PAX3 gene causing Waardenburg syndrome type 1 and type 2. ( 8490648 )
1993
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
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 21)
id 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

ClinVar genetic disease variations for Waardenburg Syndrome, Type 1:

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

id Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription, DNA-templated GO:0045893 9.43 MITF PAX3 SOX10
2 regulation of transcription from RNA polymerase II promoter GO:0006357 9.33 MITF PAX3 SOX10
3 neural crest cell migration GO:0001755 8.96 EDN3 SOX10
4 melanocyte differentiation GO:0030318 8.8 EDN3 MITF SOX10

Sources for Waardenburg Syndrome, Type 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
Content
Loading form....