MCID: WRD033
MIFTS: 51

Waardenburg Syndrome, Type 2e

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

Aliases & Classifications for Waardenburg Syndrome, Type 2e

MalaCards integrated aliases for Waardenburg Syndrome, Type 2e:

Name: Waardenburg Syndrome, Type 2e 57
Waardenburg Syndrome Type 2 76 53 59 29 73
Waardenburg Syndrome, Type 2e, with or Without Neurologic Involvement 57 13 40
Waardenburg Syndrome Type 2e 12 29 6
Ws2e 57 12 75
Hypogonadotropic Hypogonadism with Anosmia and Deafness with or Without Hypopigmentation 12 75
Waardenburg Syndrome Type 2e with or Without Neurologic Involvement 12 75
Waardenburg Syndrome, Type Iie 57 73
Waardenburg Syndrome Type Iie 12 75
Hypogonadotropic Hypogonadism with Anosmia and Deafness, with or Without Hypopigmentation 57
Kallmann Syndrome and Deafness with or Without Hypopigmentation 75
Waardenburg Syndrome Type 2e, Without Neurologic Involvement 6
Ws2e with or Without Neurological Involvement 12
Ws2e, with or Without Neurologic Involvement 57
Ws2e with or Without Neurologic Involvement 75
Waardenburg Syndrome Type Ii 59
Waardenburg Syndrome 2e 75
Ws Type 2 53
Ws 2 53
Ws2 59

Characteristics:

Orphanet epidemiological data:

59
waardenburg syndrome type 2
Inheritance: Autosomal dominant; Age of onset: Neonatal; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
variable phenotype
genetic heterogeneity
incomplete penetrance of some features


HPO:

32
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 : 53 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 waardenburg syndrome, type 2a. An important gene associated with Waardenburg Syndrome, Type 2e is SOX10 (SRY-Box 10), and among its related pathways/superpathways are Aldosterone synthesis and secretion and Pathways in cancer. Affiliated tissues include skin, eye and olfactory bulb, and related phenotypes are ptosis 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 : 57 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 : 75 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 : 76 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 31)
# Related Disease Score Top Affiliating Genes
1 waardenburg syndrome, type 4c 32.2 POLR2F SOX10
2 waardenburg syndrome, type 2a 31.7 EDNRB MITF
3 waardenburg's syndrome 26.7 EDNRB KITLG MITF SNAI2 SOX10
4 albinism, ocular, with sensorineural deafness 11.7
5 waardenburg syndrome, type 4b 11.2
6 albinism, oculocutaneous, type ib 11.1
7 waardenburg syndrome, type 2d 11.0
8 waardenburg syndrome, type 2b 10.9
9 waardenburg syndrome, type 2c 10.9
10 peripheral demyelinating neuropathy, central dysmyelination, waardenburg syndrome, and hirschsprung disease 10.3 POLR2F SOX10
11 waardenburg syndrome, type 1 10.0 MITF SOX10
12 malignant spindle cell melanoma 10.0 MITF SOX10
13 breast angiosarcoma 10.0 MITF SOX10
14 tietz albinism-deafness syndrome 10.0 MITF SOX10
15 dyschromatosis symmetrica hereditaria 9.9 MITF SOX10
16 ocular albinism 9.9
17 microphthalmia 9.9
18 albinism 9.9
19 dowling-degos disease 1 9.8 KITLG MITF
20 colonic disease 9.7 EDNRB SOX10
21 mast cell disease 9.7 KITLG MITF
22 intestinal pseudo-obstruction 9.6 EDNRB SOX10
23 megacolon 9.5 EDNRB SOX10
24 neurofibroma 9.5 KITLG MITF SOX10
25 vitiligo-associated multiple autoimmune disease susceptibility 1 9.5 KITLG MITF
26 piebald trait 9.3 KITLG MITF SNAI2
27 waardenburg syndrome type 4 9.1 EDNRB MITF SOX10
28 waardenburg syndrome, type 4a 9.1 EDNRB MITF SOX10
29 melanoma, uveal 8.9 EDNRB MITF
30 hirschsprung disease 1 8.6 EDNRB MITF POLR2F SOX10
31 cochlear disease 8.5 EDNRB MITF 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

Symptoms via clinical synopsis from OMIM:

57
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

Human phenotypes related to Waardenburg Syndrome, Type 2e:

59 32 (show all 30)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ptosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0000508
2 sensorineural hearing impairment 59 32 frequent (33%) Frequent (79-30%) HP:0000407
3 hypopigmented skin patches 59 32 frequent (33%) Frequent (79-30%) HP:0001053
4 telecanthus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000506
5 heterochromia iridis 59 32 frequent (33%) Frequent (79-30%) HP:0001100
6 premature graying of hair 59 32 hallmark (90%) Very frequent (99-80%) HP:0002216
7 aganglionic megacolon 59 32 occasional (7.5%) Occasional (29-5%) HP:0002251
8 abnormality of the kidney 59 32 occasional (7.5%) Occasional (29-5%) HP:0000077
9 white forelock 59 32 frequent (33%) Frequent (79-30%) HP:0002211
10 abnormality of the pulmonary artery 59 32 occasional (7.5%) Occasional (29-5%) HP:0004414
11 pectus excavatum 32 HP:0000767
12 nystagmus 32 HP:0000639
13 intellectual disability 32 HP:0001249
14 hearing impairment 59 Very frequent (99-80%)
15 global developmental delay 32 HP:0001263
16 hypertonia 32 HP:0001276
17 hypopigmentation of hair 59 Very frequent (99-80%)
18 blue irides 32 HP:0000635
19 hypoplasia of the iris 32 HP:0007676
20 hypopigmentation of the fundus 32 HP:0007894
21 aplasia of the semicircular canal 32 HP:0011381
22 white eyebrow 32 HP:0002226
23 white eyelashes 32 HP:0002227
24 ocular albinism 32 occasional (7.5%) HP:0001107
25 anosmia 32 occasional (7.5%) HP:0000458
26 cafe-au-lait spot 32 HP:0000957
27 muscular hypotonia of the trunk 32 HP:0008936
28 cerebral hypomyelination 32 HP:0006808
29 hypoplasia of the semicircular canal 32 HP:0011382
30 dilated vestibule of the inner ear 32 HP:0011379

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

46
# 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 SOX10 EDNRB KITLG MITF SNAI2
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 29 SOX10
2 Waardenburg Syndrome Type 2 29

Anatomical Context for Waardenburg Syndrome, Type 2e

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

41
Skin, Eye, Olfactory Bulb, Brain, Kidney, Bone

Publications for Waardenburg Syndrome, Type 2e

Articles related to Waardenburg Syndrome, Type 2e:

(show all 21)
# Title Authors Year
1
Allelic Mutations of KITLG, Encoding KIT Ligand, Cause Asymmetric and Unilateral Hearing Loss and Waardenburg Syndrome Type 2. ( 26522471 )
2015
2
Hearing dysfunction in heterozygous Mitf(Mi-wh) /+ mice, a model for Waardenburg syndrome type 2 and Tietz syndrome. ( 23020089 )
2013
3
Screening of MITF and SOX10 regulatory regions in Waardenburg syndrome type 2. ( 22848661 )
2012
4
Functional analysis of MITF gene mutations associated with Waardenburg syndrome type 2. ( 23098757 )
2012
5
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
6
[Mutation screening of MITF gene in patients with Waardenburg syndrome type 2]. ( 18424413 )
2008
7
Deletions at the SOX10 gene locus cause Waardenburg syndrome types 2 and 4. ( 17999358 )
2007
8
Waardenburg syndrome type 2 in an African patient. ( 16394488 )
2005
9
[Clinical features of a Chinese pedigree with Waardenburg syndrome type 2]. ( 16324295 )
2005
10
Three cases of Waardenburg syndrome type 2 in a Korean family. ( 15635834 )
2004
11
Clinical findings in Japanese patients with Waardenburg syndrome type 2. ( 12586183 )
2003
12
Waardenburg syndrome type 2 in a Turkish family: implications for the importance of the pattern of fundus pigmentation. ( 11702731 )
2001
13
Ser298 of MITF, a mutation site in Waardenburg syndrome type 2, is a phosphorylation site with functional significance. ( 10587587 )
2000
14
Mutation at the anophthalmic white locus in Syrian hamsters: haploinsufficiency in the Mitf gene mimics human Waardenburg syndrome type 2. ( 9499424 )
1998
15
A PAX3 polymorphism (T315K) in a family exhibiting Waardenburg syndrome type 2. ( 9584079 )
1998
16
Apparent digenic inheritance of Waardenburg syndrome type 2 (WS2) and autosomal recessive ocular albinism (AROA). ( 9158138 )
1997
17
Ectopic expression of MITF, a gene for Waardenburg syndrome type 2, converts fibroblasts to cells with melanocyte characteristics. ( 8782819 )
1996
18
A novel mutation in the MITF gene causes Waardenburg syndrome type 2. ( 8880147 )
1996
19
A gene for Waardenburg syndrome type 2 maps close to the human homologue of the microphthalmia gene at chromosome 3p12-p14.1. ( 7951321 )
1994
20
Waardenburg syndrome type 2 caused by mutations in the human microphthalmia (MITF) gene. ( 7874167 )
1994
21
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:

75
# 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 16)
# 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 GRCh37 Chromosome 22, 38379321: 38379573
4 SOX10 NM_006941.3(SOX10): c.219_428+43del deletion Pathogenic 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.113delG (p.Gly38Alafs) deletion Pathogenic rs397515387 GRCh37 Chromosome 22, 38379679: 38379679
12 SOX10 NM_006941.3(SOX10): c.113delG (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

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 transcription elongation from RNA polymerase II promoter GO:0006368 9.32 POLR2F SOX10
2 neural crest cell migration GO:0001755 9.26 EDNRB KITLG
3 negative regulation of apoptotic process GO:0043066 9.26 EDNRB KITLG MITF SNAI2
4 melanocyte differentiation GO:0030318 9.16 EDNRB MITF
5 pigmentation GO:0043473 8.8 EDNRB MITF SNAI2

Molecular functions related to Waardenburg Syndrome, Type 2e 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 8.96 MITF SNAI2
2 chromatin binding GO:0003682 8.8 MITF SNAI2 SOX10

Sources for Waardenburg Syndrome, Type 2e

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 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 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
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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