WS4C
MCID: WRD024
MIFTS: 42

Waardenburg Syndrome, Type 4c (WS4C)

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

Aliases & Classifications for Waardenburg Syndrome, Type 4c

MalaCards integrated aliases for Waardenburg Syndrome, Type 4c:

Name: Waardenburg Syndrome, Type 4c 57 13 70
Waardenburg Syndrome Type 4c 12 29 6 15
Ws4c 57 12 72
Waardenburg Syndrome with Hirschsprung Disease Type 4c 12 72
Waardenburg Syndrome Type Ivc 12 72
Waardenburg Syndrome with Hirschsprung Disease, Type 4c 57
Hirschsprung Disease with Pigmentary Anomaly 72
Waardenburg Syndrome, Type Ivc 57
Syndrome, Waardenburg, Type 4c 39
Waardenburg Syndrome, Type 4a 70
Waardenburg-Shah Syndrome 72
Shah-Waardenburg Syndrome 72
Waardenburg Syndrome 4c 72

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal dominant

Miscellaneous:
genetic heterogeneity
variable severity, intrafamilial
incomplete penetrance of some features
patients with neurologic manifestations and sox10 mutations have the neurologic variant (pcwh, )


HPO:

31
waardenburg syndrome, type 4c:
Inheritance autosomal dominant inheritance heterogeneous


Classifications:



External Ids:

Disease Ontology 12 DOID:0110955
OMIM® 57 613266
OMIM Phenotypic Series 57 PS193500
MeSH 44 D014849
MedGen 41 C2750452
UMLS 70 C1848519 C2750452

Summaries for Waardenburg Syndrome, Type 4c

OMIM® : 57 Waardenburg syndrome type 4 is an auditory-pigmentary syndrome characterized by pigmentary abnormalities of the eye, deafness, and Hirschsprung disease (review by Read and Newton, 1997). WS type 4C is caused by mutation in the SOX10 gene (602229). WS type 4 is genetically heterogeneous (see WS4A; 277580). For a description of other clinical variants of Waardenburg syndrome, see WS1 (193500), WS2 (193510), and WS3 (148820). (613266) (Updated 20-May-2021)

MalaCards based summary : Waardenburg Syndrome, Type 4c, also known as waardenburg syndrome type 4c, is related to waardenburg syndrome type 4 and peripheral demyelinating neuropathy, central dysmyelination, waardenburg syndrome, and hirschsprung disease. An important gene associated with Waardenburg Syndrome, Type 4c is SOX10 (SRY-Box Transcription Factor 10), and among its related pathways/superpathways are Neural Crest Differentiation and Regulation of retinoblastoma protein. Affiliated tissues include eye, olfactory bulb and bone, and related phenotypes are anosmia and lacrimal gland hypoplasia

Disease Ontology : 12 A Waardenburg's syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes, congenital sensorineural hearing loss, and Hirschsprung disease that has material basis in heterozygous mutation in the SOX10 gene on chromosome 22q13.

UniProtKB/Swiss-Prot : 72 Waardenburg syndrome 4C: A disorder characterized by the association of Waardenburg features (depigmentation and deafness) with the absence of enteric ganglia in the distal part of the intestine (Hirschsprung disease).

Related Diseases for Waardenburg Syndrome, Type 4c

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 4c via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 63)
# Related Disease Score Top Affiliating Genes
1 waardenburg syndrome type 4 31.6 SOX10 POLR2F MITF EDNRB EDN3
2 peripheral demyelinating neuropathy, central dysmyelination, waardenburg syndrome, and hirschsprung disease 31.5 SOX10 POLR2F PAX3 MITF EDNRB EDN3
3 waardenburg syndrome, type 4a 31.4 SOX10 POLR2F PAX3 MITF EDNRB EDN3
4 waardenburg syndrome, type 4b 31.1 SOX10 PAX3 MITF EDNRB EDN3
5 intestinal obstruction 30.1 EDNRB EDN3
6 megacolon 29.9 SOX10 PAX3 EDNRB EDN3
7 sensorineural hearing loss 29.9 SOX10 PAX3 MITF EDN3
8 waardenburg's syndrome 29.3 SOX10 POLR2F PAX3 MITF EDNRB EDN3
9 hirschsprung disease 1 29.3 SOX10 POLR2F PAX3 MITF EDNRB EDN3
10 waardenburg syndrome, type 2e 29.1 SOX10 POLR2F PAX3 MITF EDNRB EDN3
11 branchiootic syndrome 1 10.4
12 catatrichy 10.3
13 hypogonadotropic hypogonadism 10.3
14 hypogonadism 10.3
15 kallmann syndrome 10.3
16 constipation 10.3
17 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.1
18 down syndrome 10.1
19 distal arthrogryposis 10.1
20 cholelithiasis 10.1
21 leukodystrophy 10.1
22 short bowel syndrome 10.1
23 microphthalmia 10.1
24 hydrocephalus 10.1
25 acute chest syndrome 10.1
26 dermatitis 10.1
27 irritant dermatitis 10.1
28 hemoglobinopathy 10.1
29 food allergy 10.1
30 mutism 10.1
31 demyelinating polyneuropathy 10.1
32 peripheral nervous system disease 10.1
33 neuropathy 10.1
34 sickle cell disease 10.1
35 hypotonia 10.1
36 avascular necrosis 10.1
37 congenital amyoplasia 10.1
38 gallbladder melanoma 10.1 SOX10 MITF
39 crest syndrome 10.1 SOX10 EDNRB
40 malignant choroid melanoma 10.1 SOX10 MITF
41 malignant spindle cell melanoma 10.1 SOX10 MITF
42 goldberg-shprintzen syndrome 10.0 EDNRB EDN3
43 mowat-wilson syndrome 10.0 SOX10 EDNRB
44 ocular albinism with congenital sensorineural deafness 10.0 PAX3 MITF
45 large congenital melanocytic nevus 10.0 SOX10 MITF
46 albinism, ocular, with late-onset sensorineural deafness 10.0 PAX3 MITF
47 melanoma in congenital melanocytic nevus 10.0 SOX10 MITF
48 clear cell sarcoma 9.9 SOX10 MITF
49 cochlear disease 9.9 SOX10 EDNRB EDN3
50 intestinal pseudo-obstruction 9.9 SOX10 EDNRB EDN3

Graphical network of the top 20 diseases related to Waardenburg Syndrome, Type 4c:



Diseases related to Waardenburg Syndrome, Type 4c

Symptoms & Phenotypes for Waardenburg Syndrome, Type 4c

Human phenotypes related to Waardenburg Syndrome, Type 4c:

31 (show all 13)
# Description HPO Frequency HPO Source Accession
1 anosmia 31 occasional (7.5%) HP:0000458
2 lacrimal gland hypoplasia 31 occasional (7.5%) HP:0007732
3 sensorineural hearing impairment 31 HP:0000407
4 cryptorchidism 31 HP:0000028
5 blue irides 31 HP:0000635
6 premature graying of hair 31 HP:0002216
7 aganglionic megacolon 31 HP:0002251
8 heterochromia iridis 31 HP:0001100
9 hypopigmented skin patches 31 HP:0001053
10 white forelock 31 HP:0002211
11 white eyebrow 31 HP:0002226
12 white eyelashes 31 HP:0002227
13 hypogonadism 31 HP:0000135

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Genitourinary External Genitalia Male:
cryptorchidism
hypogonadism

Skin Nails Hair Skin:
hypopigmented skin patches

Head And Neck Ears:
deafness, sensorineural
enlarged vestibule
small cochlea
abnormally shaped cochlea
hypoplasia or agenesis of the semicircular canals

Head And Neck Nose:
anosmia (in some patients)

Head And Neck Mouth:
parotid gland hypoplasia (in some patients)

Head And Neck Eyes:
heterochromia iridis
bright blue irides
lacrimal gland hypoplasia (in some patients)

Skin Nails Hair Hair:
white forelock
white eyelashes
white eyebrows
premature graying

Abdomen Gastrointestinal:
hirschsprung disease
decreased myenteric and submucosal ganglia in the bowel

Skeletal Skull:
bilateral temporal bone abnormalities

Neurologic Central Nervous System:
olfactory bulb agenesis (in some patients)

Clinical features from OMIM®:

613266 (Updated 20-May-2021)

MGI Mouse Phenotypes related to Waardenburg Syndrome, Type 4c:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 hearing/vestibular/ear MP:0005377 9.46 EDNRB KRT71 MITF PAX3
2 integument MP:0010771 9.43 EDN3 EDNRB KRT71 MITF PAX3 SOX10
3 pigmentation MP:0001186 9.02 EDN3 EDNRB MITF PAX3 SOX10

Drugs & Therapeutics for Waardenburg Syndrome, Type 4c

Search Clinical Trials , NIH Clinical Center for Waardenburg Syndrome, Type 4c

Genetic Tests for Waardenburg Syndrome, Type 4c

Genetic tests related to Waardenburg Syndrome, Type 4c:

# Genetic test Affiliating Genes
1 Waardenburg Syndrome Type 4c 29 SOX10

Anatomical Context for Waardenburg Syndrome, Type 4c

MalaCards organs/tissues related to Waardenburg Syndrome, Type 4c:

40
Eye, Olfactory Bulb, Bone

Publications for Waardenburg Syndrome, Type 4c

Articles related to Waardenburg Syndrome, Type 4c:

(show all 11)
# Title Authors PMID Year
1
Deletions at the SOX10 gene locus cause Waardenburg syndrome types 2 and 4. 57 6
17999358 2007
2
The Sox10(Dom) mouse: modeling the genetic variation of Waardenburg-Shah (WS4) syndrome. 6 57
10077527 1999
3
SOX10 mutations in patients with Waardenburg-Hirschsprung disease. 57 6
9462749 1998
4
Hearing loss in Waardenburg syndrome: a systematic review. 57
26100139 2016
5
Spectrum of temporal bone abnormalities in patients with Waardenburg syndrome and SOX10 mutations. 57
23237859 2013
6
A de novo missense mutation in the gene encoding the SOX10 transcription factor in a Spanish sporadic case of Waardenburg syndrome type IV. 6
18348274 2008
7
SOX10 mutations in chronic intestinal pseudo-obstruction suggest a complex physiopathological mechanism. 57
12189494 2002
8
Sox10 mutation disrupts neural crest development in Dom Hirschsprung mouse model. 57
9425902 1998
9
Waardenburg syndrome. 57
9279758 1997
10
A novel SOX10 variant in a Japanese girl with Waardenburg syndrome type 4C and Kallmann syndrome. 61
33419966 2020
11
A novel SOX10 variant in a Japanese girl with Waardenburg syndrome type 4C and Kallmann syndrome. 61
33082981 2020

Variations for Waardenburg Syndrome, Type 4c

ClinVar genetic disease variations for Waardenburg Syndrome, Type 4c:

6 (show all 34)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 POLR2F , SOX10 NM_001301130.2(POLR2F):c.294-8155C>A SNV Pathogenic 7393 rs74315514 GRCh37: 22:38374006-38374006
GRCh38: 22:37977999-37977999
2 POLR2F , SOX10 NM_001301130.2(POLR2F):c.294-2618G>C SNV Pathogenic 7394 rs73415876 GRCh37: 22:38379543-38379543
GRCh38: 22:37983536-37983536
3 POLR2F , SOX10 NM_001301130.2(POLR2F):c.294-8073_294-8072insAGGAGC Insertion Pathogenic 7395 rs397515366 GRCh37: 22:38374088-38374089
GRCh38: 22:37978081-37978082
4 POLR2F , SOX10 NM_001301130.2(POLR2F):c.293+6651_293+6652del Microsatellite Pathogenic 7396 rs397515367 GRCh37: 22:38369825-38369826
GRCh38: 22:37973818-37973819
5 POLR2F , SOX10 NM_001301130.2(POLR2F):c.294-8211G>C SNV Pathogenic 7401 rs281797260 GRCh37: 22:38373950-38373950
GRCh38: 22:37977943-37977943
6 POLR2F , SOX10 NM_006941.3(SOX10):c.1129C>T (p.Gln377Ter) SNV Pathogenic 7402 rs74315520 GRCh37: 22:38369774-38369774
GRCh38: 22:37973767-37973767
7 POLR2F , SOX10 NM_006941.4(SOX10):c.698-740_1085delinsCCT Indel Pathogenic 7404 GRCh37: 22:38369818-38370945
GRCh38: 22:37973811-37974938
8 POLR2F , SOX10 NM_001301130.2(POLR2F):c.294-8060G>A SNV Pathogenic 7408 rs121909117 GRCh37: 22:38374101-38374101
GRCh38: 22:37978094-37978094
9 POLR2F , SOX10 NM_006941.3(SOX10):c.127C>T (p.Arg43Ter) SNV Pathogenic 547774 rs1555939523 GRCh37: 22:38379665-38379665
GRCh38: 22:37983658-37983658
10 POLR2F , SOX10 NM_006941.3(SOX10):c.1090C>T (p.Gln364Ter) SNV Pathogenic 547785 rs1555937400 GRCh37: 22:38369813-38369813
GRCh38: 22:37973806-37973806
11 overlap with 12 genes GRCh38/hg38 22q13.1(chr22:37805546-37983784)x1 copy number loss Pathogenic 545010 GRCh37: 22:38201553-38379791
GRCh38: 22:37805546-37983784
12 POLR2F , SOX10 NM_006941.4(SOX10):c.89C>A (p.Ser30Ter) SNV Pathogenic 871833 GRCh37: 22:38379703-38379703
GRCh38: 22:37983696-37983696
13 POLR2F , SOX10 NM_006941.4(SOX10):c.570C>A (p.Cys190Ter) SNV Pathogenic 1065048 GRCh37: 22:38374001-38374001
GRCh38: 22:37977994-37977994
14 POLR2F , SOX10 NM_001301130.2(POLR2F):c.293+6519_293+6523del Deletion Pathogenic 518422 rs1569167586 GRCh37: 22:38369694-38369698
GRCh38: 22:37973687-37973691
15 POLR2F , SOX10 NM_006941.4(SOX10):c.979del (p.Ala327fs) Deletion Likely pathogenic 804231 GRCh37: 22:38369924-38369924
GRCh38: 22:37973917-37973917
16 POLR2F , SOX10 NM_006941.4(SOX10):c.404G>A (p.Ser135Asn) SNV Likely pathogenic 816906 rs74315515 GRCh37: 22:38379388-38379388
GRCh38: 22:37983381-37983381
17 POLR2F , SOX10 NM_001301130.2(POLR2F):c.293+6634dup Duplication Likely pathogenic 547786 rs1555937395 GRCh37: 22:38369807-38369808
GRCh38: 22:37973800-37973801
18 POLR2F , SOX10 NM_001301130.2(POLR2F):c.293+6619del Deletion Likely pathogenic 503991 rs1555937390 GRCh37: 22:38369796-38369796
GRCh38: 22:37973789-37973789
19 POLR2F , SOX10 NM_001301130.2(POLR2F):c.294-2507del Deletion Likely pathogenic 422859 rs1064796049 GRCh37: 22:38379651-38379651
GRCh38: 22:37983644-37983644
20 POLR2F , SOX10 NM_001301130.2(POLR2F):c.294-2644_294-2640del Deletion Likely pathogenic 133303 rs483353057 GRCh37: 22:38379517-38379521
GRCh38: 22:37983510-37983514
21 POLR2F , SOX10 NM_001301130.2(POLR2F):c.294-2642_294-2623dup Duplication Likely pathogenic 547775 rs1555939476 GRCh37: 22:38379517-38379518
GRCh38: 22:37983510-37983511
22 POLR2F , SOX10 NM_001301130.2(POLR2F):c.294-2669_294-2667delinsCC Indel Likely pathogenic 547776 rs1555939460 GRCh37: 22:38379492-38379494
GRCh38: 22:37983485-37983487
23 POLR2F , SOX10 NM_006941.3(SOX10):c.301A>T (p.Lys101Ter) SNV Likely pathogenic 547777 rs1555939459 GRCh37: 22:38379491-38379491
GRCh38: 22:37983484-37983484
24 POLR2F , SOX10 NM_006941.3(SOX10):c.364C>G (p.Leu122Val) SNV Likely pathogenic 547779 rs1555939426 GRCh37: 22:38379428-38379428
GRCh38: 22:37983421-37983421
25 POLR2F , SOX10 NM_001301130.2(POLR2F):c.294-2747dup Duplication Likely pathogenic 547780 rs1555939421 GRCh37: 22:38379411-38379412
GRCh38: 22:37983404-37983405
26 POLR2F , SOX10 NM_006941.3(SOX10):c.426G>C (p.Trp142Cys) SNV Likely pathogenic 547781 rs1555939403 GRCh37: 22:38379366-38379366
GRCh38: 22:37983359-37983359
27 POLR2F , SOX10 NM_006941.3(SOX10):c.452G>C (p.Arg151Pro) SNV Likely pathogenic 547782 rs1373797370 GRCh37: 22:38374119-38374119
GRCh38: 22:37978112-37978112
28 POLR2F , SOX10 NM_006941.3(SOX10):c.586G>T (p.Glu196Ter) SNV Likely pathogenic 547783 rs763210407 GRCh37: 22:38373985-38373985
GRCh38: 22:37977978-37977978
29 POLR2F , SOX10 NM_001301130.2(POLR2F):c.293+6792dup Duplication Likely pathogenic 547784 rs1555937463 GRCh37: 22:38369968-38369969
GRCh38: 22:37973961-37973962
30 POLR2F , SOX10 NM_006941.3(SOX10):c.334A>G (p.Met112Val) SNV Uncertain significance 547778 rs1555939439 GRCh37: 22:38379458-38379458
GRCh38: 22:37983451-37983451
31 POLR2F , SOX10 NM_006941.4(SOX10):c.211T>G (p.Cys71Gly) SNV Uncertain significance 229266 rs200683397 GRCh37: 22:38379581-38379581
GRCh38: 22:37983574-37983574
32 POLR2F , SOX10 NM_006941.4(SOX10):c.718A>C (p.Thr240Pro) SNV Uncertain significance 931522 GRCh37: 22:38370185-38370185
GRCh38: 22:37974178-37974178
33 POLR2F , SOX10 NM_006941.3(SOX10):c.334A>G (p.Met112Val) SNV Uncertain significance 547778 rs1555939439 GRCh37: 22:38379458-38379458
GRCh38: 22:37983451-37983451
34 POLR2F , SOX10 NM_006941.4(SOX10):c.1081G>A (p.Ala361Thr) SNV Likely benign 982663 GRCh37: 22:38369822-38369822
GRCh38: 22:37973815-37973815

UniProtKB/Swiss-Prot genetic disease variations for Waardenburg Syndrome, Type 4c:

72
# Symbol AA change Variation ID SNP ID
1 SOX10 p.Arg106Trp VAR_066747
2 SOX10 p.Leu145Pro VAR_066750
3 SOX10 p.Ala157Val VAR_066752 rs121909117

Expression for Waardenburg Syndrome, Type 4c

Search GEO for disease gene expression data for Waardenburg Syndrome, Type 4c.

Pathways for Waardenburg Syndrome, Type 4c

Pathways related to Waardenburg Syndrome, Type 4c according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.14 SOX10 PAX3 MITF
2 11 PAX3 MITF
3 10.88 EDNRB EDN3
4 10.41 SOX10 PAX3 MITF

GO Terms for Waardenburg Syndrome, Type 4c

Biological processes related to Waardenburg Syndrome, Type 4c according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transcription elongation from RNA polymerase II promoter GO:0006368 9.43 SOX10 POLR2F
2 pigmentation GO:0043473 9.4 MITF EDNRB
3 peripheral nervous system development GO:0007422 9.37 SOX10 EDNRB
4 vasoconstriction GO:0042310 9.32 EDNRB EDN3
5 enteric nervous system development GO:0048484 9.26 SOX10 EDNRB
6 vein smooth muscle contraction GO:0014826 9.16 EDNRB EDN3
7 neural crest cell migration GO:0001755 9.13 SOX10 EDNRB EDN3
8 melanocyte differentiation GO:0030318 8.92 SOX10 MITF EDNRB EDN3

Sources for Waardenburg Syndrome, Type 4c

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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