MCID: WRD024
MIFTS: 35

Waardenburg Syndrome, Type 4c

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

Aliases & Classifications for Waardenburg Syndrome, Type 4c

MalaCards integrated aliases for Waardenburg Syndrome, Type 4c:

Name: Waardenburg Syndrome, Type 4c 57 13 40 73
Waardenburg Syndrome Type 4c 12 29 6
Ws4c 57 12 75
Waardenburg Syndrome with Hirschsprung Disease Type 4c 12 75
Waardenburg Syndrome Type Ivc 12 75
Waardenburg Syndrome with Hirschsprung Disease, Type 4c 57
Hirschsprung Disease with Pigmentary Anomaly 75
Waardenburg Syndrome, Type Ivc 57
Waardenburg Syndrome, Type 4a 73
Waardenburg-Shah Syndrome 75
Shah-Waardenburg Syndrome 75
Waardenburg Syndrome 4c 75

Characteristics:

OMIM:

57
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:

32
waardenburg syndrome, type 4c:
Inheritance heterogeneous autosomal dominant inheritance


Classifications:



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)

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 syndrome, type 4a. An important gene associated with Waardenburg Syndrome, Type 4c is SOX10 (SRY-Box 10). Affiliated tissues include eye, skin and olfactory bulb, and related phenotypes are cryptorchidism and hypogonadism

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 : 75 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

Symptoms via clinical synopsis from OMIM:

57
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

Human phenotypes related to Waardenburg Syndrome, Type 4c:

32 (show all 13)
# Description HPO Frequency HPO Source Accession
1 cryptorchidism 32 HP:0000028
2 hypogonadism 32 HP:0000135
3 sensorineural hearing impairment 32 HP:0000407
4 anosmia 32 occasional (7.5%) HP:0000458
5 blue irides 32 HP:0000635
6 hypopigmented skin patches 32 HP:0001053
7 heterochromia iridis 32 HP:0001100
8 white forelock 32 HP:0002211
9 premature graying of hair 32 HP:0002216
10 white eyebrow 32 HP:0002226
11 white eyelashes 32 HP:0002227
12 aganglionic megacolon 32 HP:0002251
13 lacrimal gland hypoplasia 32 occasional (7.5%) HP:0007732

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

26 (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 29 SOX10

Anatomical Context for Waardenburg Syndrome, Type 4c

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

41
Eye, Skin, Olfactory Bulb, Bone

Publications for Waardenburg Syndrome, Type 4c

Articles related to Waardenburg Syndrome, Type 4c:

# Title Authors Year
1
Clinical variability of Waardenburg-Shah syndrome in patients with proximal 13q deletion syndrome including the endothelin-B receptor locus. ( 19764031 )
2009
2
Long segment Hirschsprung's disease in the Waardenburg-Shah syndrome. ( 12811477 )
2003
3
Novel mutations of SOX10 suggest a dominant negative role in Waardenburg-Shah syndrome. ( 11546831 )
2001
4
Direct regulation of the Microphthalmia promoter by Sox10 links Waardenburg-Shah syndrome (WS4)-associated hypopigmentation and deafness to WS2. ( 10973953 )
2000

Variations for Waardenburg Syndrome, Type 4c

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

75
# 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 all 18)
# Gene Variation Type Significance SNP ID Assembly Location
1 SOX10 NM_006941.3(SOX10): c.565G> T (p.Glu189Ter) single nucleotide variant Pathogenic rs74315514 GRCh38 Chromosome 22, 37977999: 37977999
2 SOX10 NM_006941.3(SOX10): c.565G> T (p.Glu189Ter) single nucleotide variant Pathogenic rs74315514 GRCh37 Chromosome 22, 38374006: 38374006
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

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 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
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44 MeSH
45 MESH via Orphanet
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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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