WS2E
MCID: WRD033
MIFTS: 53

Waardenburg Syndrome, Type 2e (WS2E)

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

Aliases & Classifications for Waardenburg Syndrome, Type 2e

MalaCards integrated aliases for Waardenburg Syndrome, Type 2e:

Name: Waardenburg Syndrome, Type 2e 58
Waardenburg Syndrome Type 2 77 54 60 30 6 74
Waardenburg Syndrome Type 2e 12 30 6 15
Waardenburg Syndrome, Type 2e, with or Without Neurologic Involvement 58 13 41
Ws2e 58 12 76
Hypogonadotropic Hypogonadism with Anosmia and Deafness with or Without Hypopigmentation 12 76
Waardenburg Syndrome Type 2e with or Without Neurologic Involvement 12 76
Waardenburg Syndrome, Type Iie 58 74
Waardenburg Syndrome Type Iie 12 76
Hypogonadotropic Hypogonadism with Anosmia and Deafness, with or Without Hypopigmentation 58
Kallmann Syndrome and Deafness with or Without Hypopigmentation 76
Waardenburg Syndrome Type 2e, Without Neurologic Involvement 6
Ws2e with or Without Neurological Involvement 12
Ws2e, with or Without Neurologic Involvement 58
Ws2e with or Without Neurologic Involvement 76
Waardenburg Syndrome Type Ii 60
Waardenburg Syndrome 2e 76
Ws Type 2 54
Ws 2 54
Ws-2 17
Ws2 60

Characteristics:

Orphanet epidemiological data:

60
waardenburg syndrome type 2
Inheritance: Autosomal dominant; Age of onset: Neonatal; Age of death: normal life expectancy;

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
variable phenotype
genetic heterogeneity
incomplete penetrance of some features


HPO:

33
waardenburg syndrome, type 2e:
Onset and clinical course phenotypic variability
Inheritance heterogeneous autosomal dominant inheritance


Classifications:



Summaries for Waardenburg Syndrome, Type 2e

NIH Rare Diseases : 54 Waardenburg syndrome type 2 (WS2) is a type of Waardenburg syndrome characterized by varying degrees of deafness and pigmentation (coloring) abnormalities of the eyes, hair and/or skin. WS2 differs from type 1 and some other types of WS by the absence of dystopia canthorum (lateral displacement of the inner canthi of the eyes). Sensorineural hearing loss occurs in the majority of people with WS2, and heterochromia iridis (differences in eye coloring) occurs in about half. Progressive hearing loss has also been reported in some people with WS2. WS2 may be caused by changes (mutations) in any of several genes, but in many cases the genetic cause is unknown. While inheritance is usually autosomal dominant, sometimes WS2 is not inherited, occurring for the first time in someone with no family history of the condition. Treatment may include the use of hearing aids and/or cosmetic products or treatments (if desired) for skin hypopigmentation. Waardenburg syndrome type 2 can be further divided into subtypes based on the genetic cause, when the responsible gene can be identified.

MalaCards based summary : Waardenburg Syndrome, Type 2e, also known as waardenburg syndrome type 2, is related to waardenburg syndrome, type 4c and albinism, ocular, with late-onset sensorineural deafness. An important gene associated with Waardenburg Syndrome, Type 2e is SOX10 (SRY-Box 10), and among its related pathways/superpathways are Pathways in cancer and Kit receptor signaling pathway. Affiliated tissues include skin, eye and olfactory bulb, and related phenotypes are premature graying of hair and sensorineural hearing impairment

Disease Ontology : 12 A Waardenburg's syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes, congenital sensorineural hearing loss, and absence of lateral displacement of the inner canthus of each eye that has material basis in heterozygous mutations in the SOX10 gene on chromosome 22q13.

OMIM : 58 Waardenburg syndrome type 2 is an auditory-pigmentary syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes; congenital sensorineural hearing loss; and the absence of 'dystopia canthorum,' the lateral displacement of the inner canthus of each eye, which is seen in some other forms of WS (review by Read and Newton, 1997). Individuals with WS type 2E, which is caused by mutation in the SOX10 gene (602229), may have neurologic abnormalities, including mental impairment, myelination defects, and ataxia. Waardenburg syndrome type 2 is genetically heterogeneous (see WS2A; 193510). For a description of other clinical variants of Waardenburg syndrome, see WS1 (193500), WS3 (148820), and WS4 (277580). (611584)

UniProtKB/Swiss-Prot : 76 Waardenburg syndrome 2E: An autosomal dominant auditory-pigmentary disorder characterized by sensorineural deafness, pigmentary disturbances of the hair, skin and eyes, and absence of dystopia canthorum which is the lateral displacement of the inner canthus of each eye. Individuals with WS2E may have neurologic abnormalities, including mental impairment, myelination defects, and ataxia. Some patients can manifest features of Kallmann syndrome.

Wikipedia : 77 Waardenburg syndrome is a rare genetic disorder most often characterized by varying degrees of deafness,... more...

Related Diseases for Waardenburg Syndrome, Type 2e

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 2e via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 43)
# Related Disease Score Top Affiliating Genes
1 waardenburg syndrome, type 4c 32.2 POLR2F SOX10
2 albinism, ocular, with late-onset sensorineural deafness 31.8 MITF SOX10
3 waardenburg syndrome, type 2a 31.6 EDNRB MITF SNAI2 SOX10
4 waardenburg syndrome, type 4b 31.0 EDNRB MITF SNAI2 SOX10
5 tietz albinism-deafness syndrome 29.9 MITF SOX10
6 waardenburg's syndrome 28.0 EDNRB KITLG MITF POLR2F SNAI2 SOX10
7 albinism, ocular, with sensorineural deafness 11.9
8 albinism, oculocutaneous, type ib 11.2
9 waardenburg syndrome, type 2d 11.2
10 waardenburg syndrome, type 2b 11.0
11 waardenburg syndrome, type 2c 11.0
12 primary orthostatic tremor 10.3
13 rapidly involuting congenital hemangioma 10.2
14 isolated optic neuritis 10.1
15 malignant spindle cell melanoma 10.0 MITF SOX10
16 waardenburg syndrome, type 3 10.0 MITF SOX10
17 intraocular pressure quantitative trait locus 10.0
18 ocular albinism 10.0
19 microphthalmia 10.0
20 albinism 10.0
21 streptococcal group a invasive disease 10.0
22 nodular lymphocyte predominant hodgkin lymphoma 10.0
23 breast angiosarcoma 10.0 MITF SOX10
24 pseudoxanthoma elasticum 10.0
25 albinism-deafness syndrome 10.0
26 dilated cardiomyopathy 10.0
27 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.0
28 intestinal pseudo-obstruction 9.9 EDNRB SOX10
29 spindle cell hemangioma 9.9
30 dyschromatosis symmetrica hereditaria 9.9 MITF SOX10
31 megacolon 9.9 EDNRB SOX10
32 dowling-degos disease 1 9.9 KITLG MITF
33 colonic disease 9.9 EDNRB SOX10
34 vitiligo-associated multiple autoimmune disease susceptibility 1 9.9 KITLG MITF
35 waardenburg syndrome type 4 9.7 EDNRB MITF SOX10
36 waardenburg syndrome, type 4a 9.7 EDNRB MITF SOX10
37 neurofibroma 9.7 KITLG MITF SOX10
38 mastocytosis 9.6 KITLG MITF
39 piebald trait 9.5 KITLG MITF SNAI2
40 hirschsprung disease 1 9.5 EDNRB MITF POLR2F SOX10
41 cochlear disease 9.3 EDNRB MITF SNAI2 SOX10
42 waardenburg syndrome, type 1 9.3 EDNRB MITF SNAI2 SOX10
43 peripheral demyelinating neuropathy, central dysmyelination, waardenburg syndrome, and hirschsprung disease 9.0 EDNRB MITF POLR2F SNAI2 SOX10

Graphical network of the top 20 diseases related to Waardenburg Syndrome, Type 2e:



Diseases related to Waardenburg Syndrome, Type 2e

Symptoms & Phenotypes for Waardenburg Syndrome, Type 2e

Human phenotypes related to Waardenburg Syndrome, Type 2e:

60 33 (show all 31)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 premature graying of hair 60 33 hallmark (90%) Very frequent (99-80%) HP:0002216
2 sensorineural hearing impairment 60 33 frequent (33%) Frequent (79-30%) HP:0000407
3 hypopigmented skin patches 60 33 frequent (33%) Frequent (79-30%) HP:0001053
4 heterochromia iridis 60 33 frequent (33%) Frequent (79-30%) HP:0001100
5 white forelock 60 33 frequent (33%) Frequent (79-30%) HP:0002211
6 ptosis 60 33 occasional (7.5%) Occasional (29-5%) HP:0000508
7 telecanthus 60 33 occasional (7.5%) Occasional (29-5%) HP:0000506
8 aganglionic megacolon 60 33 occasional (7.5%) Occasional (29-5%) HP:0002251
9 abnormality of the kidney 60 33 occasional (7.5%) Occasional (29-5%) HP:0000077
10 abnormality of the pulmonary artery 60 33 occasional (7.5%) Occasional (29-5%) HP:0004414
11 ocular albinism 33 occasional (7.5%) HP:0001107
12 anosmia 33 occasional (7.5%) HP:0000458
13 pectus excavatum 33 HP:0000767
14 nystagmus 33 HP:0000639
15 intellectual disability 33 HP:0001249
16 hearing impairment 60 Very frequent (99-80%)
17 global developmental delay 33 HP:0001263
18 hypertonia 33 HP:0001276
19 hypopigmentation of hair 60 Very frequent (99-80%)
20 blue irides 33 HP:0000635
21 hypoplasia of the iris 33 HP:0007676
22 hypopigmentation of the fundus 33 HP:0007894
23 aplasia of the semicircular canal 33 HP:0011381
24 white eyebrow 33 HP:0002226
25 white eyelashes 33 HP:0002227
26 cafe-au-lait spot 33 HP:0000957
27 muscular hypotonia of the trunk 33 HP:0008936
28 cerebral hypomyelination 33 HP:0006808
29 dilatation 33 HP:0002617
30 hypoplasia of the semicircular canal 33 HP:0011382
31 dilated vestibule of the inner ear 33 HP:0011379

Symptoms via clinical synopsis from OMIM:

58
Chest External Features:
pectus excavatum

Skin Nails Hair Skin:
hypopigmented skin patches
cafe-au-lait spots
freckles

Neurologic Central Nervous System:
mental retardation
delayed psychomotor development
increased muscle tone
axial hypotonia
a subset of patients have neurologic abnormalities
more
Head And Neck Nose:
absence of the olfactory bulbs (reported in 1 patient)
anosmia (in some patients)

Skeletal Skull:
bilateral temporal bone abnormalities

Head And Neck Eyes:
nystagmus
bright blue eyes
retinal hypopigmentation
hypopigmented irides
hypoplastic irides
more
Skin Nails Hair Hair:
white forelock
white eyelashes
white eyebrows
premature graying

Head And Neck Ears:
deafness, sensorineural
small cochlea
abnormally shaped cochlea
absence of the cochlear nerves (reported in 1 patient)
hypoplasia or agenesis of the semicircular canals
more
Head And Neck Teeth:
delayed deciduous tooth eruption (reported in 1 patient)
large central incisors (reported in 1 patient)
irregularly placed dentition (reported in 1 patient)

Clinical features from OMIM:

611584

MGI Mouse Phenotypes related to Waardenburg Syndrome, Type 2e:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 embryo MP:0005380 9.8 EDNRB KITLG MITF SNAI2 SOX10
2 endocrine/exocrine gland MP:0005379 9.77 EDNRB KITLG MITF SNAI2 SOX10
3 craniofacial MP:0005382 9.76 EDNRB KITLG MITF SNAI2
4 digestive/alimentary MP:0005381 9.73 EDNRB KITLG SNAI2 SOX10
5 integument MP:0010771 9.72 EDNRB KITLG MITF SNAI2 SOX10
6 limbs/digits/tail MP:0005371 9.56 EDNRB KITLG MITF SOX10
7 nervous system MP:0003631 9.55 EDNRB KITLG MITF SNAI2 SOX10
8 pigmentation MP:0001186 9.35 EDNRB KITLG MITF SNAI2 SOX10
9 vision/eye MP:0005391 8.92 EDNRB KITLG MITF SNAI2

Drugs & Therapeutics for Waardenburg Syndrome, Type 2e

Search Clinical Trials , NIH Clinical Center for Waardenburg Syndrome, Type 2e

Genetic Tests for Waardenburg Syndrome, Type 2e

Genetic tests related to Waardenburg Syndrome, Type 2e:

# Genetic test Affiliating Genes
1 Waardenburg Syndrome Type 2e 30 SOX10
2 Waardenburg Syndrome Type 2 30

Anatomical Context for Waardenburg Syndrome, Type 2e

MalaCards organs/tissues related to Waardenburg Syndrome, Type 2e:

42
Skin, Eye, Olfactory Bulb, Brain, Kidney, Bone

Publications for Waardenburg Syndrome, Type 2e

Articles related to Waardenburg Syndrome, Type 2e:

(show all 26)
# Title Authors Year
1
Wnt signaling pathway involvement in genotypic and phenotypic variations in Waardenburg syndrome type 2 with MITF mutations. ( 29531335 )
2018
2
Waardenburg syndrome type 2. ( 30449927 )
2018
3
Functional analysis of a nonstop mutation in MITF gene identified in a patient with Waardenburg syndrome type 2. ( 28356565 )
2017
4
Pigmented macules in Waardenburg syndrome type 2 due to KITLG mutation. ( 28504826 )
2017
5
A novel mutation of the MITF gene in a family with Waardenburg syndrome type 2: A case report. ( 27073475 )
2016
6
Allelic Mutations of KITLG, Encoding KIT Ligand, Cause Asymmetric and Unilateral Hearing Loss and Waardenburg Syndrome Type 2. ( 26522471 )
2015
7
Waardenburg syndrome type 2: an orthodontic perspective. ( 26429191 )
2015
8
Hearing dysfunction in heterozygous Mitf(Mi-wh) /+ mice, a model for Waardenburg syndrome type 2 and Tietz syndrome. ( 23020089 )
2013
9
Screening of MITF and SOX10 regulatory regions in Waardenburg syndrome type 2. ( 22848661 )
2012
10
Functional analysis of MITF gene mutations associated with Waardenburg syndrome type 2. ( 23098757 )
2012
11
A 725 kb deletion at 22q13.1 chromosomal region including SOX10 gene in a boy with a neurologic variant of Waardenburg syndrome type 2. ( 22842075 )
2012
12
[Mutation screening of MITF gene in patients with Waardenburg syndrome type 2]. ( 18424413 )
2008
13
Waardenburg syndrome type 2 in an African patient. ( 16394488 )
2005
14
[Clinical features of a Chinese pedigree with Waardenburg syndrome type 2]. ( 16324295 )
2005
15
Three cases of Waardenburg syndrome type 2 in a Korean family. ( 15635834 )
2004
16
Clinical findings in Japanese patients with Waardenburg syndrome type 2. ( 12586183 )
2003
17
Waardenburg syndrome type 2 in a Turkish family: implications for the importance of the pattern of fundus pigmentation. ( 11702731 )
2001
18
Ser298 of MITF, a mutation site in Waardenburg syndrome type 2, is a phosphorylation site with functional significance. ( 10587587 )
2000
19
Mutation at the anophthalmic white locus in Syrian hamsters: haploinsufficiency in the Mitf gene mimics human Waardenburg syndrome type 2. ( 9499424 )
1998
20
A PAX3 polymorphism (T315K) in a family exhibiting Waardenburg syndrome type 2. ( 9584079 )
1998
21
Apparent digenic inheritance of Waardenburg syndrome type 2 (WS2) and autosomal recessive ocular albinism (AROA). ( 9158138 )
1997
22
Ectopic expression of MITF, a gene for Waardenburg syndrome type 2, converts fibroblasts to cells with melanocyte characteristics. ( 8782819 )
1996
23
A novel mutation in the MITF gene causes Waardenburg syndrome type 2. ( 8880147 )
1996
24
A gene for Waardenburg syndrome type 2 maps close to the human homologue of the microphthalmia gene at chromosome 3p12-p14.1. ( 7951321 )
1994
25
Waardenburg syndrome type 2 caused by mutations in the human microphthalmia (MITF) gene. ( 7874167 )
1994
26
Mutations of PAX3 unlikely in Waardenburg syndrome type 2. ( 8220430 )
1993

Variations for Waardenburg Syndrome, Type 2e

UniProtKB/Swiss-Prot genetic disease variations for Waardenburg Syndrome, Type 2e:

76
# Symbol AA change Variation ID SNP ID
1 SOX10 p.Ser135Thr VAR_021386 rs74315515
2 SOX10 p.Met112Ile VAR_066748
3 SOX10 p.Arg161His VAR_066753 rs750566714

ClinVar genetic disease variations for Waardenburg Syndrome, Type 2e:

6 (show all 24)
# Gene Variation Type Significance SNP ID Assembly Location
1 SOX10 NM_006941.3(SOX10): c.404G> C (p.Ser135Thr) single nucleotide variant Pathogenic rs74315515 GRCh37 Chromosome 22, 38379388: 38379388
2 SOX10 NM_006941.3(SOX10): c.404G> C (p.Ser135Thr) single nucleotide variant Pathogenic rs74315515 GRCh38 Chromosome 22, 37983381: 37983381
3 SOX10 NM_006941.3(SOX10): c.219_428+43del deletion Pathogenic rs1555939381 GRCh37 Chromosome 22, 38379321: 38379573
4 SOX10 NM_006941.3(SOX10): c.219_428+43del deletion Pathogenic rs1555939381 GRCh38 Chromosome 22, 37983314: 37983566
5 SOX10 NM_006941.3(SOX10): c.429-1112_697+396del deletion Pathogenic GRCh37 Chromosome 22, 38373478: 38375254
6 SOX10 NM_006941.3(SOX10): c.429-1112_697+396del deletion Pathogenic GRCh38 Chromosome 22, 37977471: 37979247
7 SOX10 NM_006941.3(SOX10): c.506delC (p.Pro169Argfs) deletion Pathogenic rs397515369 GRCh37 Chromosome 22, 38374065: 38374065
8 SOX10 NM_006941.3(SOX10): c.506delC (p.Pro169Argfs) deletion Pathogenic rs397515369 GRCh38 Chromosome 22, 37978058: 37978058
9 SOX10 NM_006941.3(SOX10): c.743_744delAG (p.Glu248Alafs) deletion Pathogenic rs397515386 GRCh37 Chromosome 22, 38370159: 38370160
10 SOX10 NM_006941.3(SOX10): c.743_744delAG (p.Glu248Alafs) deletion Pathogenic rs397515386 GRCh38 Chromosome 22, 37974152: 37974153
11 SOX10 NM_006941.3(SOX10): c.113del (p.Gly38Alafs) deletion Pathogenic rs397515387 GRCh37 Chromosome 22, 38379679: 38379679
12 SOX10 NM_006941.3(SOX10): c.113del (p.Gly38Alafs) deletion Pathogenic rs397515387 GRCh38 Chromosome 22, 37983672: 37983672
13 SOX10 NM_006941.3(SOX10): c.2T> G (p.Met1Arg) single nucleotide variant Pathogenic rs397515457 GRCh37 Chromosome 22, 38379790: 38379790
14 SOX10 NM_006941.3(SOX10): c.2T> G (p.Met1Arg) single nucleotide variant Pathogenic rs397515457 GRCh38 Chromosome 22, 37983783: 37983783
15 SOX10 NM_006941.3(SOX10): c.316C> G (p.Arg106Gly) single nucleotide variant Likely pathogenic rs1057518656 GRCh37 Chromosome 22, 38379476: 38379476
16 SOX10 NM_006941.3(SOX10): c.316C> G (p.Arg106Gly) single nucleotide variant Likely pathogenic rs1057518656 GRCh38 Chromosome 22, 37983469: 37983469
17 SOX10 NM_006941.3(SOX10): c.415G> T (p.Gly139Cys) single nucleotide variant Uncertain significance GRCh38 Chromosome 22, 37983370: 37983370
18 SOX10 NM_006941.3(SOX10): c.415G> T (p.Gly139Cys) single nucleotide variant Uncertain significance GRCh37 Chromosome 22, 38379377: 38379377
19 SOX10 NM_006941.3(SOX10): c.1169C> G (p.Ser390Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 22, 37973727: 37973727
20 SOX10 NM_006941.3(SOX10): c.1169C> G (p.Ser390Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 22, 38369734: 38369734
21 MITF NM_000248.3(MITF): c.33+5G> C single nucleotide variant Likely pathogenic GRCh38 Chromosome 3, 69936760: 69936760
22 MITF NM_000248.3(MITF): c.33+5G> C single nucleotide variant Likely pathogenic GRCh37 Chromosome 3, 69985911: 69985911
23 SOX10 NM_006941.3(SOX10): c.487C> T (p.Gln163Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 22, 37978077: 37978077
24 SOX10 NM_006941.3(SOX10): c.487C> T (p.Gln163Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 22, 38374084: 38374084

Expression for Waardenburg Syndrome, Type 2e

Search GEO for disease gene expression data for Waardenburg Syndrome, Type 2e.

Pathways for Waardenburg Syndrome, Type 2e

GO Terms for Waardenburg Syndrome, Type 2e

Biological processes related to Waardenburg Syndrome, Type 2e according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 negative regulation of canonical Wnt signaling pathway GO:0090090 9.43 SNAI2 SOX10
2 neural crest cell migration GO:0001755 9.43 EDNRB KITLG SOX10
3 transcription elongation from RNA polymerase II promoter GO:0006368 9.4 POLR2F SOX10
4 peripheral nervous system development GO:0007422 9.37 EDNRB SOX10
5 negative regulation of apoptotic process GO:0043066 9.35 EDNRB KITLG MITF SNAI2 SOX10
6 pigmentation GO:0043473 9.33 EDNRB MITF SNAI2
7 enteric nervous system development GO:0048484 9.32 EDNRB SOX10
8 melanocyte differentiation GO:0030318 8.8 EDNRB MITF SOX10

Molecular functions related to Waardenburg Syndrome, Type 2e according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA-binding transcription repressor activity, RNA polymerase II-specific GO:0001227 9.16 MITF SNAI2
2 chromatin binding GO:0003682 9.13 MITF SNAI2 SOX10
3 E-box binding GO:0070888 8.62 MITF SNAI2

Sources for Waardenburg Syndrome, Type 2e

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
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75 UMLS via Orphanet
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