MCID: WRD031
MIFTS: 34

Waardenburg Syndrome, Type 3

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

Aliases & Classifications for Waardenburg Syndrome, Type 3

MalaCards integrated aliases for Waardenburg Syndrome, Type 3:

Name: Waardenburg Syndrome, Type 3 57 53 13 40
Klein-Waardenburg Syndrome 57 12 53 59 75 55
Ws3 57 12 53 59 75
Waardenburg Syndrome with Upper Limb Anomalies 57 12 53 75
Waardenburg Syndrome Type 3 12 76 53 59
Waardenburg Syndrome Type Iii 12 59
White Forelock Syndrome with Multiple Congenital Malformations 53
Waardenburg Syndrome with Limb Anomalies 59
White Forelock with Malformations 75
Waardenburg Syndrome, Type Iii 57
Waardenburg Syndrome 3 75
Klein's Syndrome 73

Characteristics:

Orphanet epidemiological data:

59
waardenburg syndrome type 3
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Neonatal; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
autosomal recessive
autosomal dominant

Miscellaneous:
variable severity
both heterozygous and homozygous pax3 mutations have been found


HPO:

32
waardenburg syndrome, type 3:
Onset and clinical course variable expressivity
Inheritance autosomal dominant contiguous gene syndrome autosomal recessive inheritance


Classifications:



Summaries for Waardenburg Syndrome, Type 3

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 896Disease definitionWaardenburg syndrome type 3 (WS3) is a very rare subtype of Waardenburg syndrome (WS; see this term) that is characterized by limb anomalies in association with congenitalhearing loss, minor defects in structures arising from neural crest, resulting in pigmentation anomalies of eyes, hair, and skin.EpidemiologyIncidence is unknown, but WS3 is the rarest form of all Waardenburg syndrome types.Clinical descriptionWS3 is characterized by the association of limb anomalies (predominantly involving upper limbs, with hypoplasia of the musculoskeletal system, flexion contractures, fusion of the carpal bones, syndactylia) with features of Waardenburg syndrome (see this term), which include congenital sensorineural hearing loss, hypopigmentation abnormalities of irides, hair and skin and minor facial dysmorphism in combination with dystopia canthorum.EtiologyWS3 is caused by heterozygous or homozygousmutations in the PAX3 (2q36.1) gene.Diagnostic methodsDiagnosis is made through criteria of the association of WS1 manifestations with limb anomalies. PAX3 gene analysis confirms diagnosis resulting in an abnormality of melanocytes of skin, ears and hair.Antenatal diagnosisAntenatal diagnosis is possible for affected parents.Genetic counselingThe defects are more severe in homozygous than heterozygous forms. Genetic counseling is recommended.Management and treatmentHearing aids to counter hearing loss, effective therapy to improve language, communication, and cognitive skill and limbs physiotherapy are recommended. Associated manifestations are treated as appropriate (e.g. skin and eyes protection from the sun).PrognosisDue to the very few number of cases described so far, information on prognosis and quality of life is limited. Disease progression is variable, with symptoms being more severe in homozygous than in heterozygous forms.Visit the Orphanet disease page for more resources.

MalaCards based summary : Waardenburg Syndrome, Type 3, also known as klein-waardenburg syndrome, is related to white forelock with malformations and waardenburg syndrome, type 2b. An important gene associated with Waardenburg Syndrome, Type 3 is PAX3 (Paired Box 3). Affiliated tissues include skin, eye and bone, and related phenotypes are intellectual disability and hearing impairment

Disease Ontology : 12 A Waardenburg's syndrome characterized by upper limb anomalies, congenital hearing loss, dystopia canthorum and pigmentation anomalies of eyes, hair, and skin that has material basis in heterozygous or homozygous mutation in the PAX3 gene on chromosome 2q36.

OMIM : 57 Waardenburg syndrome type 3 is an auditory-pigmentary syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes; congenital sensorineural hearing loss; presence of 'dystopia canthorum,' the lateral displacement of the ocular inner canthi; and upper limb abnormalities (reviews by Read and Newton, 1997 and Pingault et al., 2010). WS type 3 is also referred to as 'Klein-Waardenburg syndrome' (Gorlin et al., 1976). (148820)

UniProtKB/Swiss-Prot : 75 Waardenburg syndrome 3: WS3 is an autosomal dominant disorder characterized by sensorineural deafness, pigmentary disturbances, dystopia canthorum and limb anomalies such as hypoplasia of the musculoskeletal system, flexion contractures, fusion of the carpal bones, syndactylies.

Wikipedia : 76 Waardenburg syndrome is a rare genetic disorder most often characterized by varying degrees of deafness,... more...

Related Diseases for Waardenburg Syndrome, Type 3

Graphical network of the top 20 diseases related to Waardenburg Syndrome, Type 3:



Diseases related to Waardenburg Syndrome, Type 3

Symptoms & Phenotypes for Waardenburg Syndrome, Type 3

Symptoms via clinical synopsis from OMIM:

57
Skeletal Hands:
clinodactyly
brachydactyly
syndactyly, cutaneous
finger contractures
hypoplasia of the hand muscles

Head And Neck Eyes:
blepharophimosis
synophrys
dystopia canthorum
heterochromia iridis (complete or partial)
hypopigmented iris
more
Skeletal Feet:
syndactyly

Head And Neck Ears:
sensorineural deafness

Skeletal Limbs:
contractures of the upper limb joints
hypoplasia of the bones of the upper limbs and wrists

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

Skin Nails Hair Hair:
white forelock
premature graying of the hair

Head And Neck Face:
prognathism

Head And Neck Nose:
prominent nasal root
hypoplastic alae

Neurologic Central Nervous System:
mental retardation (reported in 1 patient)
spasticity (reported in 1 patient)


Clinical features from OMIM:

148820

Human phenotypes related to Waardenburg Syndrome, Type 3:

59 32 (show all 39)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 59 32 occasional (7.5%) Occasional (29-5%) HP:0001249
2 hearing impairment 59 32 hallmark (90%) Very frequent (99-80%) HP:0000365
3 joint stiffness 59 32 hallmark (90%) Very frequent (99-80%) HP:0001387
4 microcephaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0000252
5 thick eyebrow 59 32 hallmark (90%) Very frequent (99-80%) HP:0000574
6 acrocyanosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0001063
7 atrial septal defect 59 32 occasional (7.5%) Occasional (29-5%) HP:0001631
8 telecanthus 59 32 frequent (33%) Frequent (79-30%) HP:0000506
9 downslanted palpebral fissures 59 32 hallmark (90%) Very frequent (99-80%) HP:0000494
10 atelectasis 59 32 frequent (33%) Frequent (79-30%) HP:0100750
11 blepharophimosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0000581
12 narrow nasal bridge 59 32 hallmark (90%) Very frequent (99-80%) HP:0000446
13 spastic paraplegia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001258
14 tracheomalacia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002779
15 synostosis of carpal bones 59 32 hallmark (90%) Very frequent (99-80%) HP:0005048
16 cutaneous finger syndactyly 59 32 hallmark (90%) Very frequent (99-80%) HP:0010554
17 tented upper lip vermilion 59 32 hallmark (90%) Very frequent (99-80%) HP:0010804
18 white hair 59 32 frequent (33%) Frequent (79-30%) HP:0011364
19 camptodactyly of finger 59 32 occasional (7.5%) Occasional (29-5%) HP:0100490
20 clinodactyly 32 HP:0030084
21 mandibular prognathia 32 HP:0000303
22 wide nasal bridge 32 HP:0000431
23 sensorineural hearing impairment 32 HP:0000407
24 scapular winging 32 HP:0003691
25 hypopigmented skin patches 32 HP:0001053
26 prominent nasal bridge 32 HP:0000426
27 heterochromia iridis 32 HP:0001100
28 premature graying of hair 32 HP:0002216
29 aganglionic megacolon 32 HP:0002251
30 abnormality of the face 59 Very frequent (99-80%)
31 blue irides 32 HP:0000635
32 brachydactyly 32 HP:0001156
33 white forelock 32 HP:0002211
34 abnormality of finger 59 Very frequent (99-80%)
35 abnormality of the upper limb 59 Very frequent (99-80%)
36 synophrys 32 HP:0000664
37 partial albinism 32 HP:0007443
38 carpal synostosis 32 HP:0009702
39 joint contracture of the hand 32 HP:0009473

Drugs & Therapeutics for Waardenburg Syndrome, Type 3

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Pathway Study WS3 - Home Based Metacognitive Therapy for Cardiac Rehabilitation Patients Active, not recruiting NCT03129282 Not Applicable

Search NIH Clinical Center for Waardenburg Syndrome, Type 3

Genetic Tests for Waardenburg Syndrome, Type 3

Anatomical Context for Waardenburg Syndrome, Type 3

MalaCards organs/tissues related to Waardenburg Syndrome, Type 3:

41
Skin, Eye, Bone

Publications for Waardenburg Syndrome, Type 3

Articles related to Waardenburg Syndrome, Type 3:

# Title Authors Year
1
Waardenburg syndrome type 3 (Klein-Waardenburg syndrome) segregating with a heterozygous deletion in the paired box domain of PAX3: a simple variant or a true syndrome? ( 11683776 )
2001
2
Myelomeningocele and Waardenburg syndrome (type 3) in patients with interstitial deletions of 2q35 and the PAX3 gene: possible digenic inheritance of a neural tube defect. ( 9482647 )
1998
3
Mutations in the paired domain of the human PAX3 gene cause Klein- Waardenburg syndrome (WS-III) as well as Waardenburg syndrome type I (WS-I). ( 8447316 )
1993
4
Autosomal dominant inheritance of Klein-Waardenburg syndrome. ( 1536170 )
1992
5
Upper limb involvement in the Klein-Waardenburg syndrome. ( 7091186 )
1982
6
Anal atresia and the Klein-Waardenburg syndrome. ( 7241550 )
1981

Variations for Waardenburg Syndrome, Type 3

UniProtKB/Swiss-Prot genetic disease variations for Waardenburg Syndrome, Type 3:

75
# Symbol AA change Variation ID SNP ID
1 PAX3 p.Asn47His VAR_003791 rs104893653
2 PAX3 p.Ser84Phe VAR_003801 rs104893651
3 PAX3 p.Arg270Cys VAR_013619
4 PAX3 p.Tyr90His VAR_017535 rs104893654

ClinVar genetic disease variations for Waardenburg Syndrome, Type 3:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 PAX3 NM_001127366.2(PAX3): c.251C> T (p.Ser84Phe) single nucleotide variant Pathogenic rs104893651 GRCh37 Chromosome 2, 223161767: 223161767
2 PAX3 NM_001127366.2(PAX3): c.251C> T (p.Ser84Phe) single nucleotide variant Pathogenic rs104893651 GRCh38 Chromosome 2, 222297048: 222297048
3 PAX3 NM_181457.3(PAX3): c.139A> C (p.Asn47His) single nucleotide variant Pathogenic rs104893653 GRCh37 Chromosome 2, 223161879: 223161879
4 PAX3 NM_181457.3(PAX3): c.139A> C (p.Asn47His) single nucleotide variant Pathogenic rs104893653 GRCh38 Chromosome 2, 222297160: 222297160
5 PAX3 PAX3, 13-BP DEL, NT384 deletion Pathogenic
6 PAX3 NM_181457.3(PAX3): c.268T> C (p.Tyr90His) single nucleotide variant Pathogenic rs104893654 GRCh37 Chromosome 2, 223161750: 223161750
7 PAX3 NM_181457.3(PAX3): c.268T> C (p.Tyr90His) single nucleotide variant Pathogenic rs104893654 GRCh38 Chromosome 2, 222297031: 222297031

Expression for Waardenburg Syndrome, Type 3

Search GEO for disease gene expression data for Waardenburg Syndrome, Type 3.

Pathways for Waardenburg Syndrome, Type 3

GO Terms for Waardenburg Syndrome, Type 3

Sources for Waardenburg Syndrome, Type 3

3 CDC
7 CNVD
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10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
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31 HMDB
32 HPO
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34 ICD10 via Orphanet
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45 MESH via Orphanet
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54 NINDS
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57 OMIM
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62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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