WS4C
MCID: WRD024
MIFTS: 37

Waardenburg Syndrome, Type 4c (WS4C)

Categories: Ear diseases, Eye diseases, Fetal 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 58 13 41 74
Waardenburg Syndrome Type 4c 12 30 6
Ws4c 58 12 76
Waardenburg Syndrome with Hirschsprung Disease Type 4c 12 76
Waardenburg Syndrome Type Ivc 12 76
Waardenburg Syndrome with Hirschsprung Disease, Type 4c 58
Hirschsprung Disease with Pigmentary Anomaly 76
Waardenburg Syndrome, Type Ivc 58
Waardenburg Syndrome, Type 4a 74
Waardenburg-Shah Syndrome 76
Shah-Waardenburg Syndrome 76
Waardenburg Syndrome 4c 76

Characteristics:

OMIM:

58
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:

33
waardenburg syndrome, type 4c:
Inheritance heterogeneous autosomal dominant inheritance


Classifications:



Summaries for Waardenburg Syndrome, Type 4c

OMIM : 58 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)

MalaCards based summary : Waardenburg Syndrome, Type 4c, also known as waardenburg syndrome type 4c, is related to peripheral demyelinating neuropathy, central dysmyelination, waardenburg syndrome, and hirschsprung disease and waardenburg's syndrome. An important gene associated with Waardenburg Syndrome, Type 4c is SOX10 (SRY-Box 10). Affiliated tissues include eye, skin 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 : 76 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

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:

33 (show all 13)
# Description HPO Frequency HPO Source Accession
1 anosmia 33 occasional (7.5%) HP:0000458
2 lacrimal gland hypoplasia 33 occasional (7.5%) HP:0007732
3 sensorineural hearing impairment 33 HP:0000407
4 cryptorchidism 33 HP:0000028
5 hypopigmented skin patches 33 HP:0001053
6 hypogonadism 33 HP:0000135
7 heterochromia iridis 33 HP:0001100
8 premature graying of hair 33 HP:0002216
9 aganglionic megacolon 33 HP:0002251
10 blue irides 33 HP:0000635
11 white forelock 33 HP:0002211
12 white eyebrow 33 HP:0002226
13 white eyelashes 33 HP:0002227

Symptoms via clinical synopsis from OMIM:

58
Genitourinary External Genitalia Male:
cryptorchidism
hypogonadism

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

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)

Skin Nails Hair Skin:
hypopigmented skin patches

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

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

27 (show all 14)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-103 9.7 SOX10
2 Increased shRNA abundance (Z-score > 2) GR00366-A-115 9.7 SOX10
3 Increased shRNA abundance (Z-score > 2) GR00366-A-177 9.7 POLR2F SOX10
4 Increased shRNA abundance (Z-score > 2) GR00366-A-32 9.7 SOX10
5 Increased shRNA abundance (Z-score > 2) GR00366-A-43 9.7 POLR2F
6 Increased shRNA abundance (Z-score > 2) GR00366-A-49 9.7 SOX10
7 Increased shRNA abundance (Z-score > 2) GR00366-A-7 9.7 SOX10
8 Increased shRNA abundance (Z-score > 2) GR00366-A-70 9.7 SOX10
9 Increased shRNA abundance (Z-score > 2) GR00366-A-81 9.7 SOX10
10 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.7 SOX10
11 Decreased viability GR00240-S-1 9.46 POLR2F SOX10
12 Decreased viability GR00402-S-2 9.46 POLR2F SOX10
13 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-1 9.23 POLR2F SOX10
14 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-2 9.23 POLR2F 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 30 SOX10

Anatomical Context for Waardenburg Syndrome, Type 4c

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

42
Eye, Skin, Bone, Olfactory Bulb

Publications for Waardenburg Syndrome, Type 4c

Articles related to Waardenburg Syndrome, Type 4c:

# Title Authors Year
1
The additional genetic diagnosis of homozygous sickle cell disease in a patient with Waardenburg-Shah syndrome: a case report. ( 30636638 )
2019
2
A recalcitrant case of Jacquet erosive diaper dermatitis after surgery for Hirschsprung disease in a boy with Waardenburg-Shah syndrome. ( 30142718 )
2018
3
Clinical variability of Waardenburg-Shah syndrome in patients with proximal 13q deletion syndrome including the endothelin-B receptor locus. ( 19764031 )
2009
4
Long segment Hirschsprung's disease in the Waardenburg-Shah syndrome. ( 12811477 )
2003
5
Novel mutations of SOX10 suggest a dominant negative role in Waardenburg-Shah syndrome. ( 11546831 )
2001
6
Direct regulation of the Microphthalmia promoter by Sox10 links Waardenburg-Shah syndrome (WS4)-associated hypopigmentation and deafness to WS2. ( 10973953 )
2000
7
Near-total intestinal aganglionosis in the Waardenburg-Shah syndrome. ( 10626872 )
1999

Variations for Waardenburg Syndrome, Type 4c

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

76
# 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

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

6 (show top 50) (show all 54)
# Gene Variation Type Significance SNP ID Assembly Location
1 SOX10 NM_006941.3(SOX10): c.565G> T (p.Glu189Ter) single nucleotide variant Pathogenic rs74315514 GRCh37 Chromosome 22, 38374006: 38374006
2 SOX10 NM_006941.3(SOX10): c.565G> T (p.Glu189Ter) single nucleotide variant Pathogenic rs74315514 GRCh38 Chromosome 22, 37977999: 37977999
3 SOX10 NM_006941.3(SOX10): c.249C> G (p.Tyr83Ter) single nucleotide variant Pathogenic rs73415876 GRCh37 Chromosome 22, 38379543: 38379543
4 SOX10 NM_006941.3(SOX10): c.249C> G (p.Tyr83Ter) single nucleotide variant Pathogenic rs73415876 GRCh38 Chromosome 22, 37983536: 37983536
5 SOX10 NM_006941.3(SOX10): c.482_483insGCTCCT (p.Arg161_Met162insLeuLeu) insertion Pathogenic rs397515366 GRCh37 Chromosome 22, 38374088: 38374089
6 SOX10 NM_006941.3(SOX10): c.482_483insGCTCCT (p.Arg161_Met162insLeuLeu) insertion Pathogenic rs397515366 GRCh38 Chromosome 22, 37978081: 37978082
7 SOX10 NM_006941.3(SOX10): c.1077_1078delGA (p.Glu359Aspfs) deletion Pathogenic rs397515367 GRCh37 Chromosome 22, 38369825: 38369826
8 SOX10 NM_006941.3(SOX10): c.1077_1078delGA (p.Glu359Aspfs) deletion Pathogenic rs397515367 GRCh38 Chromosome 22, 37973818: 37973819
9 SOX10 NM_006941.3(SOX10): c.621C> G (p.Tyr207Ter) single nucleotide variant Pathogenic rs281797260 GRCh37 Chromosome 22, 38373950: 38373950
10 SOX10 NM_006941.3(SOX10): c.621C> G (p.Tyr207Ter) single nucleotide variant Pathogenic rs281797260 GRCh38 Chromosome 22, 37977943: 37977943
11 SOX10 NM_006941.3(SOX10): c.1129C> T (p.Gln377Ter) single nucleotide variant Pathogenic rs74315520 GRCh37 Chromosome 22, 38369774: 38369774
12 SOX10 NM_006941.3(SOX10): c.1129C> T (p.Gln377Ter) single nucleotide variant Pathogenic rs74315520 GRCh38 Chromosome 22, 37973767: 37973767
13 SOX10 NM_006941.3(SOX10): c.698-740_1085del1128insCCT indel Pathogenic GRCh37 Chromosome 22, 38369818: 38370945
14 SOX10 NM_006941.3(SOX10): c.698-740_1085del1128insCCT indel Pathogenic GRCh38 Chromosome 22, 37973811: 37974938
15 SOX10 NM_006941.3(SOX10): c.470C> T (p.Ala157Val) single nucleotide variant Pathogenic rs121909117 GRCh37 Chromosome 22, 38374101: 38374101
16 SOX10 NM_006941.3(SOX10): c.470C> T (p.Ala157Val) single nucleotide variant Pathogenic rs121909117 GRCh38 Chromosome 22, 37978094: 37978094
17 SOX10 NM_006941.3(SOX10): c.271_275delCCCGT (p.Pro91Alafs) deletion Likely pathogenic rs483353057 GRCh37 Chromosome 22, 38379517: 38379521
18 SOX10 NM_006941.3(SOX10): c.271_275delCCCGT (p.Pro91Alafs) deletion Likely pathogenic rs483353057 GRCh38 Chromosome 22, 37983510: 37983514
19 SOX10 NM_006941.3(SOX10): c.211T> G (p.Cys71Gly) single nucleotide variant Uncertain significance rs200683397 GRCh37 Chromosome 22, 38379581: 38379581
20 SOX10 NM_006941.3(SOX10): c.211T> G (p.Cys71Gly) single nucleotide variant Uncertain significance rs200683397 GRCh38 Chromosome 22, 37983574: 37983574
21 SOX10 NM_006941.3(SOX10): c.141delG (p.Pro48Glnfs) deletion Pathogenic/Likely pathogenic rs1064796049 GRCh38 Chromosome 22, 37983644: 37983644
22 SOX10 NM_006941.3(SOX10): c.141delG (p.Pro48Glnfs) deletion Pathogenic/Likely pathogenic rs1064796049 GRCh37 Chromosome 22, 38379651: 38379651
23 SOX10 NM_006941.3(SOX10): c.1107delC (p.Tyr369Terfs) deletion Pathogenic/Likely pathogenic rs1555937390 GRCh38 Chromosome 22, 37973789: 37973789
24 SOX10 NM_006941.3(SOX10): c.1107delC (p.Tyr369Terfs) deletion Pathogenic/Likely pathogenic rs1555937390 GRCh37 Chromosome 22, 38369796: 38369796
25 SOX10 NM_006941.3(SOX10): c.1205_1209del (p.Tyr402Terfs) deletion Pathogenic GRCh37 Chromosome 22, 38369694: 38369698
26 SOX10 NM_006941.3(SOX10): c.1205_1209del (p.Tyr402Terfs) deletion Pathogenic GRCh38 Chromosome 22, 37973687: 37973691
27 subset of 12 genes:SOX10 GRCh38/hg38 22q13.1(chr22: 37805546-37983784)x1 copy number loss Pathogenic GRCh37 Chromosome 22, 38201553: 38379791
28 subset of 12 genes:SOX10 GRCh38/hg38 22q13.1(chr22: 37805546-37983784)x1 copy number loss Pathogenic GRCh38 Chromosome 22, 37805546: 37983784
29 SOX10 NM_006941.3(SOX10): c.1095dup (p.Pro366Alafs) duplication Likely pathogenic rs1555937395 GRCh37 Chromosome 22, 38369808: 38369808
30 SOX10 NM_006941.3(SOX10): c.1095dup (p.Pro366Alafs) duplication Likely pathogenic rs1555937395 GRCh38 Chromosome 22, 37973801: 37973801
31 SOX10 NM_006941.3(SOX10): c.1090C> T (p.Gln364Ter) single nucleotide variant Pathogenic rs1555937400 GRCh38 Chromosome 22, 37973806: 37973806
32 SOX10 NM_006941.3(SOX10): c.1090C> T (p.Gln364Ter) single nucleotide variant Pathogenic rs1555937400 GRCh37 Chromosome 22, 38369813: 38369813
33 SOX10 NM_006941.3(SOX10): c.934dup (p.Ser312Lysfs) duplication Likely pathogenic rs1555937463 GRCh37 Chromosome 22, 38369969: 38369969
34 SOX10 NM_006941.3(SOX10): c.934dup (p.Ser312Lysfs) duplication Likely pathogenic rs1555937463 GRCh38 Chromosome 22, 37973962: 37973962
35 SOX10 NM_006941.3(SOX10): c.586G> T (p.Glu196Ter) single nucleotide variant Likely pathogenic rs763210407 GRCh38 Chromosome 22, 37977978: 37977978
36 SOX10 NM_006941.3(SOX10): c.586G> T (p.Glu196Ter) single nucleotide variant Likely pathogenic rs763210407 GRCh37 Chromosome 22, 38373985: 38373985
37 SOX10 NM_006941.3(SOX10): c.452G> C (p.Arg151Pro) single nucleotide variant Likely pathogenic rs1373797370 GRCh37 Chromosome 22, 38374119: 38374119
38 SOX10 NM_006941.3(SOX10): c.452G> C (p.Arg151Pro) single nucleotide variant Likely pathogenic rs1373797370 GRCh38 Chromosome 22, 37978112: 37978112
39 SOX10 NM_006941.3(SOX10): c.426G> C (p.Trp142Cys) single nucleotide variant Likely pathogenic rs1555939403 GRCh37 Chromosome 22, 38379366: 38379366
40 SOX10 NM_006941.3(SOX10): c.426G> C (p.Trp142Cys) single nucleotide variant Likely pathogenic rs1555939403 GRCh38 Chromosome 22, 37983359: 37983359
41 SOX10 NM_006941.3(SOX10): c.380dup (p.His128Alafs) duplication Likely pathogenic rs1555939421 GRCh37 Chromosome 22, 38379412: 38379412
42 SOX10 NM_006941.3(SOX10): c.380dup (p.His128Alafs) duplication Likely pathogenic rs1555939421 GRCh38 Chromosome 22, 37983405: 37983405
43 SOX10 NM_006941.3(SOX10): c.364C> G (p.Leu122Val) single nucleotide variant Likely pathogenic rs1555939426 GRCh37 Chromosome 22, 38379428: 38379428
44 SOX10 NM_006941.3(SOX10): c.364C> G (p.Leu122Val) single nucleotide variant Likely pathogenic rs1555939426 GRCh38 Chromosome 22, 37983421: 37983421
45 SOX10 NM_006941.3(SOX10): c.334A> G (p.Met112Val) single nucleotide variant Uncertain significance rs1555939439 GRCh37 Chromosome 22, 38379458: 38379458
46 SOX10 NM_006941.3(SOX10): c.334A> G (p.Met112Val) single nucleotide variant Uncertain significance rs1555939439 GRCh38 Chromosome 22, 37983451: 37983451
47 SOX10 NM_006941.3(SOX10): c.301A> T (p.Lys101Ter) single nucleotide variant Likely pathogenic rs1555939459 GRCh37 Chromosome 22, 38379491: 38379491
48 SOX10 NM_006941.3(SOX10): c.301A> T (p.Lys101Ter) single nucleotide variant Likely pathogenic rs1555939459 GRCh38 Chromosome 22, 37983484: 37983484
49 SOX10 NM_006941.3(SOX10): c.298_300delAGCinsGG (p.Ser100Glyfs) indel Likely pathogenic rs1555939460 GRCh37 Chromosome 22, 38379492: 38379494
50 SOX10 NM_006941.3(SOX10): c.298_300delAGCinsGG (p.Ser100Glyfs) indel Likely pathogenic rs1555939460 GRCh38 Chromosome 22, 37983485: 37983487

Expression for Waardenburg Syndrome, Type 4c

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

Pathways for Waardenburg Syndrome, Type 4c

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 8.62 POLR2F SOX10

Sources for Waardenburg Syndrome, Type 4c

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
73 Tocris
74 UMLS
75 UMLS via Orphanet
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