MCID: EPD030
MIFTS: 43

Epidermolysis Bullosa Simplex, Localized

Categories: Genetic diseases, Rare diseases, Skin diseases

Aliases & Classifications for Epidermolysis Bullosa Simplex, Localized

MalaCards integrated aliases for Epidermolysis Bullosa Simplex, Localized:

Name: Epidermolysis Bullosa Simplex, Localized 57 53
Epidermolysis Bullosa Simplex, Weber-Cockayne Type 57 53 59 75
Epidermolysis Bullosa of Hands and Feet 57 53 13
Epidermolysis Bullosa Simplex of Palms and Soles 53 59
Weber-Cockayne Syndrome 53 73
Ebs-Loc 53 59
Weber-Cockayne Type Epidermolysis Bullosa Simplex 53
Localized Epidermolysis Bullosa Simplex 59
Ebs, Acral Form 57
Wc-Ebs 75

Characteristics:

Orphanet epidemiological data:

59
localized epidermolysis bullosa simplex
Inheritance: Autosomal dominant; Age of onset: Childhood; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
disease exacerbation during summer due to heat
onset in early childhood or adolescence
early adult onset has been reported


HPO:

32
epidermolysis bullosa simplex, localized:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 59  
Rare skin diseases


Summaries for Epidermolysis Bullosa Simplex, Localized

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 79400Disease definitionLocalized epidermolysis bullosa simplex, formerly known as EBS, Weber-Cockayne, is a basal subtype of epidermolysis bullosa simplex (EBS, see this term). The disease is characterized by blisters occurring mainly on the palms and soles, exacerbated by warm weather.EpidemiologyReported prevalence ranges from 1/318,000 for localized EBS in the United States to 1/35,000 for localized EBS and non-Dowling-Meara generalized EBS (combined) in Scotland. About two-thirds of EBS patients have the localized basal form.Clinical descriptionOnset is usually in late infancy or early childhood. The usual distribution of blisters in these patients is on the palms and soles, although other skin surfaces may also blister if subjected to significant trauma. Milia and scarring are rare in localized EBS, and dystrophic nails are uncommon. Focal keratoderma of the palms and soles may occur by adulthood in some patients. The only common extracutaneous finding in localized EBS, i.e. localized intraoral erosions or blisters, tends to be asymptomatic, occurs in about one third of patients, and is usually seen only during infancy.EtiologyLocalized EBS is caused by dominant negative mutations within either the KRT5 (12q13.13) or KRT14 (17q12-q21) genes, encoding keratin 5 and keratin 14, respectively.Genetic counselingTransmission is autosomal dominant and sporadic cases are frequent.PrognosisAlthough the disease can be disabling, life-expectancy is normal.Visit the Orphanet disease page for more resources.

MalaCards based summary : Epidermolysis Bullosa Simplex, Localized, also known as epidermolysis bullosa simplex, weber-cockayne type, is related to epidermolysis bullosa simplex and epidermolysis bullosa. An important gene associated with Epidermolysis Bullosa Simplex, Localized is KRT5 (Keratin 5), and among its related pathways/superpathways are Keratinization and Cytoskeleton remodeling Neurofilaments. The drugs Everolimus and Miconazole have been mentioned in the context of this disorder. Affiliated tissues include skin, and related phenotypes are hyperhidrosis and bruising susceptibility

OMIM : 57 Epidermolysis bullosa simplex is a clinically and genetically heterogeneous skin disorder characterized by blistering of the skin following minor physical trauma as a result of cytolysis within the basal epidermal cells. Most forms show autosomal dominant inheritance. The localized form is characterized by localized blistering primarily on the hands and feet (Pfendner et al., 2005). The other 2 main types of EBS include the milder generalized Koebner type (131900) and the more severe Dowling-Meara type (131760). All 3 forms can be caused by mutation in the KRT5 or KRT14 genes (summary by Fine et al., 2008). (131800)

UniProtKB/Swiss-Prot : 75 Epidermolysis bullosa simplex, Weber-Cockayne type: A form of intraepidermal epidermolysis bullosa characterized by blistering limited to palmar and plantar areas of the skin.

Related Diseases for Epidermolysis Bullosa Simplex, Localized

Diseases in the Epidermolysis Bullosa Simplex family:

Epidermolysis Bullosa Simplex, Localized Epidermolysis Bullosa Simplex, Autosomal Recessive 1
Epidermolysis Bullosa Simplex, Autosomal Recessive 2

Diseases related to Epidermolysis Bullosa Simplex, Localized via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 29)
# Related Disease Score Top Affiliating Genes
1 epidermolysis bullosa simplex 28.6 ITGB4 KRT14 KRT5
2 epidermolysis bullosa 28.5 ITGB4 KRT14 KRT5
3 epidermolysis bullosa simplex, ogna type 11.3
4 epidermolysis bullosa simplex, autosomal recessive 1 9.7 KRT14 KRT5
5 benign breast adenomyoepithelioma 9.7 KRT14 KRT5
6 lichen planopilaris 9.6 KRT14 KRT5
7 large cell acanthoma 9.6 KRT14 KRT5
8 apocrine sweat gland neoplasm 9.6 KRT14 KRT5
9 epidermolysis bullosa simplex, generalized 9.6 KRT14 KRT5
10 epidermolysis bullosa simplex with mottled pigmentation 9.6 KRT14 KRT5
11 breast squamous cell carcinoma 9.6 KRT14 KRT5
12 odontoma 9.6 KRT14 KRT5
13 breast adenomyoepithelioma 9.6 KRT14 KRT5
14 breast myoepithelial neoplasm 9.6 KRT14 KRT5
15 cervical clear cell adenocarcinoma 9.5 KRT14 KRT5
16 epidermolysis bullosa simplex, dowling-meara type 9.5 KRT14 KRT5
17 lipoadenoma 9.5 KRT14 KRT5
18 lipid-rich carcinoma 9.5 KRT14 KRT5
19 intraneural perineurioma 9.5 KRT14 KRT5
20 pre-malignant neoplasm 9.4 KRT14 KRT5
21 sweat gland cancer 9.4 KRT14 KRT5
22 skin benign neoplasm 9.4 KRT14 KRT5
23 primary cutaneous amyloidosis 9.3 KRT14 KRT5
24 ichthyosis bullosa of siemens 9.2 KRT14 KRT5
25 ductal carcinoma in situ 9.1 KRT14 KRT5
26 vesiculobullous skin disease 9.1 ITGB4 KRT14 KRT5
27 in situ carcinoma 9.1 ITGB4 KRT14 KRT5
28 skin disease 9.0 ITGB4 KRT14 KRT5
29 papilloma 8.9 KRT14 KRT5

Graphical network of the top 20 diseases related to Epidermolysis Bullosa Simplex, Localized:



Diseases related to Epidermolysis Bullosa Simplex, Localized

Symptoms & Phenotypes for Epidermolysis Bullosa Simplex, Localized

Symptoms via clinical synopsis from OMIM:

57
Skin Nails Hair Skin Electron Microscopy:
cleavage within basal keratinocytes

Skin Nails Hair Skin:
blistering, recurrent, of the palms and soles
atrophic scarring (rare)
milia (rare)
hyperkeratosis, focal, on the palms and soles (in adulthood in some)


Clinical features from OMIM:

131800

Human phenotypes related to Epidermolysis Bullosa Simplex, Localized:

59 32 (show all 10)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hyperhidrosis 59 32 frequent (33%) Frequent (79-30%) HP:0000975
2 bruising susceptibility 59 32 hallmark (90%) Very frequent (99-80%) HP:0000978
3 palmoplantar keratoderma 59 32 occasional (7.5%) Occasional (29-5%) HP:0000982
4 milia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001056
5 atrophic scars 59 32 occasional (7.5%) Occasional (29-5%) HP:0001075
6 nail dystrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0008404
7 oral mucosal blisters 59 32 occasional (7.5%) Occasional (29-5%) HP:0200097
8 abnormal blistering of the skin 59 Very frequent (99-80%)
9 hyperkeratosis 32 occasional (7.5%) HP:0000962
10 palmoplantar blistering 32 HP:0007446

MGI Mouse Phenotypes related to Epidermolysis Bullosa Simplex, Localized:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.33 KRT14 KRT5 ITGB4
2 digestive/alimentary MP:0005381 9.13 ITGB4 KRT14 KRT5
3 integument MP:0010771 8.8 ITGB4 KRT14 KRT5

Drugs & Therapeutics for Epidermolysis Bullosa Simplex, Localized

Drugs for Epidermolysis Bullosa Simplex, Localized (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 8)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Everolimus Approved Phase 2 159351-69-6 6442177
2
Miconazole Approved, Investigational, Vet_approved Phase 2 22916-47-8 4189
3
Sirolimus Approved, Investigational Phase 2 53123-88-9 5284616 6436030 46835353
4 Anti-Bacterial Agents Phase 2
5 Antibiotics, Antitubercular Phase 2
6 Antifungal Agents Phase 2
7 Anti-Infective Agents Phase 2
8 Immunosuppressive Agents Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Using Topical Sirolimus 2% for Patients With Epidermolysis Bullous Simplex (EBS) Study Recruiting NCT03016715 Phase 2 Sirolimus 2%;Vehicle
2 Using Topical Sirolimus 2% for Patients With Epidermolysis Bullous Simplex (EBS) Study Active, not recruiting NCT02960997 Phase 2 Sirolimus, 2%;Vehicle

Search NIH Clinical Center for Epidermolysis Bullosa Simplex, Localized

Genetic Tests for Epidermolysis Bullosa Simplex, Localized

Anatomical Context for Epidermolysis Bullosa Simplex, Localized

MalaCards organs/tissues related to Epidermolysis Bullosa Simplex, Localized:

41
Skin

Publications for Epidermolysis Bullosa Simplex, Localized

Articles related to Epidermolysis Bullosa Simplex, Localized:

# Title Authors Year
1
Localized epidermolysis bullosa simplex (Weber-Cockayne type). ( 22206097 )
2011
2
Treatment of epidermolysis bullosa simplex, Weber-Cockayne type, with botulinum toxin type A. ( 19153338 )
2009
3
A novel autosomal partially dominant mutation designated G476D in the keratin 5 gene causing epidermolysis bullosa simplex Weber-Cockayne type: a family study with a genetic twist. ( 17549391 )
2007
4
Epidermolysis bullosa simplex: localized (Weber-Cockayne type). ( 15690931 )
2004

Variations for Epidermolysis Bullosa Simplex, Localized

UniProtKB/Swiss-Prot genetic disease variations for Epidermolysis Bullosa Simplex, Localized:

75 (show all 39)
# Symbol AA change Variation ID SNP ID
1 KRT14 p.Val270Met VAR_003840 rs58560979
2 KRT14 p.Lys116Asn VAR_010438 rs59271739
3 KRT14 p.Asp273Gly VAR_010448 rs59375065
4 KRT14 p.Ala274Asp VAR_010449 rs58785777
5 KRT14 p.Ile377Asn VAR_010450 rs61536893
6 KRT14 p.Arg388Cys VAR_010451 rs59966597
7 KRT14 p.Glu422Lys VAR_010452 rs58762773
8 KRT14 p.Met119Val VAR_023719 rs61263401
9 KRT14 p.Val133Leu VAR_023723 rs61027685
10 KRT14 p.Leu408Met VAR_023724 rs57200223
11 KRT14 p.Arg211Pro VAR_027718 rs60589227
12 KRT14 p.Arg148Cys VAR_031636 rs58378809
13 KRT14 p.Arg388His VAR_031637 rs58645163
14 KRT14 p.Tyr415Cys VAR_031638 rs59442925
15 KRT5 p.Ile161Ser VAR_003872 rs58058996
16 KRT5 p.Asn193Lys VAR_003873 rs60586163
17 KRT5 p.Met327Thr VAR_003874 rs58072617
18 KRT5 p.Arg331Cys VAR_003875 rs61297109
19 KRT5 p.Pro152Leu VAR_010454 rs60617604
20 KRT5 p.Met327Lys VAR_010462 rs58072617
21 KRT5 p.Asp328His VAR_010463 rs56790237
22 KRT5 p.Asp328Val VAR_010464 rs57142010
23 KRT5 p.Asn329Lys VAR_010465 rs59730172
24 KRT5 p.Lys404Glu VAR_023726 rs60809982
25 KRT5 p.Ala438Asp VAR_023727 rs57845028
26 KRT5 p.Glu167Lys VAR_026536 rs57378129
27 KRT5 p.Asn177Ser VAR_026538 rs61495052
28 KRT5 p.Lys199Thr VAR_026539 rs58766676
29 KRT5 p.Leu311Pro VAR_026540 rs59864957
30 KRT5 p.Val324Asp VAR_026541 rs59335325
31 KRT5 p.Asp328Glu VAR_026542 rs59464425
32 KRT5 p.Asp328Gly VAR_026543 rs57142010
33 KRT5 p.Glu190Lys VAR_027724 rs58976397
34 KRT5 p.Arg331His VAR_027725 rs56729325
35 KRT5 p.Asp158Val VAR_031641 rs61222761
36 KRT5 p.Arg352Ser VAR_031644 rs59112594
37 KRT5 p.Val186Glu VAR_071631 rs267607457
38 KRT5 p.Thr321Pro VAR_071632
39 KRT5 p.Ala428Thr VAR_071633 rs267607458

ClinVar genetic disease variations for Epidermolysis Bullosa Simplex, Localized:

6
(show all 19)
# Gene Variation Type Significance SNP ID Assembly Location
1 KRT14 KRT14, 3-BP DEL, GLU375DEL deletion Pathogenic
2 KRT14 NM_000526.4(KRT14): c.357G> A (p.Met119Ile) single nucleotide variant Pathogenic rs57358989 GRCh37 Chromosome 17, 39742730: 39742730
3 KRT14 NM_000526.4(KRT14): c.357G> A (p.Met119Ile) single nucleotide variant Pathogenic rs57358989 GRCh38 Chromosome 17, 41586478: 41586478
4 KRT5 NM_000424.3(KRT5): c.482T> G (p.Ile161Ser) single nucleotide variant Pathogenic rs58058996 GRCh37 Chromosome 12, 52913599: 52913599
5 KRT5 NM_000424.3(KRT5): c.482T> G (p.Ile161Ser) single nucleotide variant Pathogenic rs58058996 GRCh38 Chromosome 12, 52519815: 52519815
6 KRT5 NM_000424.3(KRT5): c.980T> C (p.Met327Thr) single nucleotide variant Pathogenic rs58072617 GRCh37 Chromosome 12, 52911486: 52911486
7 KRT5 NM_000424.3(KRT5): c.980T> C (p.Met327Thr) single nucleotide variant Pathogenic rs58072617 GRCh38 Chromosome 12, 52517702: 52517702
8 KRT5 NM_000424.3(KRT5): c.987C> A (p.Asn329Lys) single nucleotide variant Pathogenic rs59730172 GRCh37 Chromosome 12, 52911479: 52911479
9 KRT5 NM_000424.3(KRT5): c.987C> A (p.Asn329Lys) single nucleotide variant Pathogenic rs59730172 GRCh38 Chromosome 12, 52517695: 52517695
10 KRT5 NM_000424.3(KRT5): c.579C> G (p.Asn193Lys) single nucleotide variant Pathogenic rs60586163 GRCh37 Chromosome 12, 52912921: 52912921
11 KRT5 NM_000424.3(KRT5): c.579C> G (p.Asn193Lys) single nucleotide variant Pathogenic rs60586163 GRCh38 Chromosome 12, 52519137: 52519137
12 KRT5 KRT5, 1-BP DEL, 1635G deletion Pathogenic
13 KRT5 NM_000424.3(KRT5): c.508G> A (p.Glu170Lys) single nucleotide variant Pathogenic rs59115483 GRCh37 Chromosome 12, 52913573: 52913573
14 KRT5 NM_000424.3(KRT5): c.508G> A (p.Glu170Lys) single nucleotide variant Pathogenic rs59115483 GRCh38 Chromosome 12, 52519789: 52519789
15 ITGB4 ITGB4, 2-BP DEL, 4733CT deletion Pathogenic
16 KRT5 NM_000424.3(KRT5): c.991C> T (p.Arg331Cys) single nucleotide variant Pathogenic rs61297109 GRCh37 Chromosome 12, 52911475: 52911475
17 KRT5 NM_000424.3(KRT5): c.991C> T (p.Arg331Cys) single nucleotide variant Pathogenic rs61297109 GRCh38 Chromosome 12, 52517691: 52517691
18 ITGB4 NM_000213.4(ITGB4): c.5329+2T> C single nucleotide variant Likely pathogenic rs762236241 GRCh37 Chromosome 17, 73753393: 73753393
19 ITGB4 NM_000213.4(ITGB4): c.5329+2T> C single nucleotide variant Likely pathogenic rs762236241 GRCh38 Chromosome 17, 75757312: 75757312

Expression for Epidermolysis Bullosa Simplex, Localized

Search GEO for disease gene expression data for Epidermolysis Bullosa Simplex, Localized.

Pathways for Epidermolysis Bullosa Simplex, Localized

Pathways related to Epidermolysis Bullosa Simplex, Localized according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.61 KRT14 KRT5
2
Show member pathways
10.99 KRT14 KRT5
3 10.54 KRT14 KRT5

GO Terms for Epidermolysis Bullosa Simplex, Localized

Cellular components related to Epidermolysis Bullosa Simplex, Localized according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 intermediate filament GO:0005882 8.96 KRT14 KRT5
2 keratin filament GO:0045095 8.62 KRT14 KRT5

Biological processes related to Epidermolysis Bullosa Simplex, Localized according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 keratinization GO:0031424 9.26 KRT14 KRT5
2 cornification GO:0070268 9.16 KRT14 KRT5
3 epidermis development GO:0008544 8.96 KRT14 KRT5
4 hemidesmosome assembly GO:0031581 8.8 ITGB4 KRT14 KRT5

Molecular functions related to Epidermolysis Bullosa Simplex, Localized according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 structural constituent of cytoskeleton GO:0005200 8.62 KRT14 KRT5

Sources for Epidermolysis Bullosa Simplex, Localized

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
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30 HGMD
31 HMDB
32 HPO
33 ICD10
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44 MeSH
45 MESH via Orphanet
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62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
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74 UMLS via Orphanet
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