K-EBS
MCID: EPD029
MIFTS: 42

Epidermolysis Bullosa Simplex, Generalized (K-EBS)

Categories: Genetic diseases, Rare diseases, Skin diseases

Aliases & Classifications for Epidermolysis Bullosa Simplex, Generalized

MalaCards integrated aliases for Epidermolysis Bullosa Simplex, Generalized:

Name: Epidermolysis Bullosa Simplex, Generalized 57 53
Epidermolysis Bullosa Simplex, Koebner Type 57 53 59 75 29 13 6 40
Ebs, Generalized 57 53
Generalized Epidermolysis Bullosa Simplex, Non-Dowling-Meara Type 59
Epidermolysis Bullosa Simplex, Generalized Non-Dowling-Meara 53
Epidermolysis Bullosa Simplex, Generalized Intermediate 59
Epidermolysis Bullosa Simplex, Köbner Type 59
Generalized Ebs, Non-Dowling-Meara Type 59
Epidermolysis Bullosa Simplex Kobner 73
Epidermolysis Bullosa Simplex 2 75
Ebs, Generalized Intermediate 59
Generalized Ebs 53
Ebs Generalized 75
Ebs-K 53
K-Ebs 75
Ebs2 75

Characteristics:

Orphanet epidemiological data:

59
epidermolysis bullosa simplex, generalized intermediate
Inheritance: Autosomal dominant,Not applicable; Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
onset at birth or in early infancy
disease exacerbation during summer due to heat
improvement with age
blistering becomes confined to the palms and soles with age


HPO:

32
epidermolysis bullosa simplex, generalized:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 59  
Rare skin diseases


External Ids:

OMIM 57 131900
Orphanet 59 ORPHA79399
MESH via Orphanet 45 C535961
ICD10 via Orphanet 34 Q81.0
UMLS via Orphanet 74 C0079299
MedGen 42 C0079299
MeSH 44 D016110
UMLS 73 C0079299

Summaries for Epidermolysis Bullosa Simplex, Generalized

OMIM : 57 Epidermolysis bullosa simplex (EBS) is a clinically and genetically heterogeneous skin disorder characterized by recurrent blistering of the skin following minor physical trauma as a result of cytolysis within basal epidermal cells. Most forms show autosomal dominant inheritance. The 3 main types include the generalized Koebner form, the more severe generalized Dowling-Meara form (131760), and the localized, mild Weber-Cockayne form (131800) (Fine et al., 2008). All 3 forms can be caused by mutation in the KRT5 or the KRT14 gene. See 601001 for a rare autosomal recessive form caused by mutation in the KRT14 gene. Davison (1965) referred to generalized distribution of bullous vesicles as epidermolysis simplex bullosa. The condition in which bullae were limited to the hands and feet was referred to as the Cockayne type of epidermolysis bullosa (131800). On the basis of an extensive study in Norway and review of the literature, Gedde-Dahl (1971) arrived at a classification of epidermolysis bullosa. EB simplex in this classification encompassed disorders characterized by bulla formation within the epidermis, basal cell vacuolization, and dissolution of tonofibrils on electron microscopy. The generalized Koebner form and the localized Weber-Cockayne type were believed to be allelic. Gedde-Dahl (1981) recognized at least 16 varieties of epidermolysis bullosa and suggested that dominant EB simplex can be clinically and genetically divided into at least 4 types: the generalized Koebner type, the localized Weber-Cockayne type, the mild Ogna type with fragile skin (131950), and a form with mottled pigmentation (131960). Fine et al. (1991) provided a revised classification of the subtypes of inherited epidermolysis bullosa based on clinical and laboratory criteria. (131900)

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

NIH Rare Diseases : 53 Epidermolysis bullosa simplex, generalized is a form of epidermolysis bullosa, a group of genetic conditions that cause the skin to be fragile and blister easily. This disorder usually presents at birth or during infancy and results in widespread blisters over the body's surface. Though it is not a common feature of this type, scarring may occur. There may also be mild involvement of mucous membranes, fingernails and toenails, and localized thickening of the skin on the soles of the feet and the palms of the hands that increases with age. All four major types of epidermolysis bullosa simplex, including the genralized type, are caused by mutations in the KRT5 and KRT14 genes. This condition is usually inherited in an autosomal dominant fashion.

UniProtKB/Swiss-Prot : 75 Epidermolysis bullosa simplex, Koebner type: A form of intraepidermal epidermolysis bullosa characterized by generalized skin blistering. The phenotype is not fundamentally distinct from the Dowling-Meara type, although it is less severe.

Related Diseases for Epidermolysis Bullosa Simplex, Generalized

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

(show all 41)
# Related Disease Score Top Affiliating Genes
1 epidermolysis bullosa simplex, dowling-meara type 32.4 KRT5 KRT14
2 epidermolysis bullosa simplex, localized 31.4 KRT5 KRT14
3 epidermolysis bullosa simplex 30.5 KRT5 KRT14 KLHL24
4 epidermolysis bullosa 30.5 KRT5 KRT14 KLHL24
5 epidermolysis bullosa simplex, generalized, with scarring and hair loss 12.8
6 epidermolysis bullosa simplex, ogna type 11.3
7 neuromuscular disease 10.1
8 skin disease 9.9 KRT5 KRT14
9 benign breast adenomyoepithelioma 9.9 KRT5 KRT14
10 breast adenomyoepithelioma 9.9 KRT5 KRT14
11 lichen planopilaris 9.9 KRT5 KRT14
12 epidermolysis bullosa simplex, autosomal recessive 1 9.9 KRT5 KRT14
13 large cell acanthoma 9.9 KRT5 KRT14
14 apocrine sweat gland neoplasm 9.9 KRT5 KRT14
15 breast squamous cell carcinoma 9.9 KRT5 KRT14
16 epidermolysis bullosa simplex with mottled pigmentation 9.9 KRT5 KRT14
17 odontoma 9.9 KRT5 KRT14
18 cervical clear cell adenocarcinoma 9.9 KRT5 KRT14
19 breast myoepithelial neoplasm 9.9 KRT5 KRT14
20 lipoadenoma 9.9 KRT5 KRT14
21 thoracic benign neoplasm 9.9 KRT5 KRT14
22 breast benign neoplasm 9.9 KRT5 KRT14
23 pregnancy adenoma 9.9 KRT5 KRT14
24 lipid-rich carcinoma 9.9 KRT5 KRT14
25 sweat gland disease 9.9 KRT5 KRT14
26 intraneural perineurioma 9.9 KRT5 KRT14
27 tonsil cancer 9.9 KRT5 KRT14
28 pre-malignant neoplasm 9.9 KRT5 KRT14
29 oropharynx cancer 9.9 KRT5 KRT14
30 in situ carcinoma 9.9 KRT5 KRT14
31 spindle cell carcinoma 9.9 KRT5 KRT14
32 skin benign neoplasm 9.9 KRT5 KRT14
33 primary cutaneous amyloidosis 9.9 KRT5 KRT14
34 sweat gland cancer 9.9 KRT5 KRT14
35 dowling-degos disease 9.8 KRT5 KRT14
36 ductal carcinoma in situ 9.8 KRT5 KRT14
37 papilloma 9.8 KRT5 KRT14
38 adenoid cystic carcinoma 9.8 KRT5 KRT14
39 basal cell carcinoma 9.8 KRT5 KRT14
40 vesiculobullous skin disease 9.7 KRT5 KRT14 KLHL24
41 cervical cancer 9.7 KRT5 KRT14

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



Diseases related to Epidermolysis Bullosa Simplex, Generalized

Symptoms & Phenotypes for Epidermolysis Bullosa Simplex, Generalized

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Mouth:
oral blistering

Skin Nails Hair Skin Electron Microscopy:
cleavage within basal keratinocytes
no clumping of keratin filaments in basal epidermal cells

Skin Nails Hair Skin:
hyperkeratosis of the palms and soles
blistering, generalized, recurrent (occurs after mild physical trauma)
milia (less common)
lack of scarring

Skin Nails Hair Nails:
dystrophic nails (less common)


Clinical features from OMIM:

131900

Human phenotypes related to Epidermolysis Bullosa Simplex, Generalized:

59 32 (show all 19)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ptosis 59 32 frequent (33%) Frequent (79-30%) HP:0000508
2 hyperhidrosis 59 32 frequent (33%) Frequent (79-30%) HP:0000975
3 failure to thrive 59 32 occasional (7.5%) Occasional (29-5%) HP:0001508
4 respiratory insufficiency 59 32 occasional (7.5%) Occasional (29-5%) HP:0002093
5 abnormality of the nail 59 32 frequent (33%) Frequent (79-30%) HP:0001597
6 generalized hyperkeratosis 59 32 frequent (33%) Frequent (79-30%) HP:0005595
7 palmoplantar keratoderma 59 32 frequent (33%) Frequent (79-30%) HP:0000982
8 abnormal blistering of the skin 59 32 hallmark (90%) Very frequent (99-80%) HP:0008066
9 ophthalmoparesis 59 32 frequent (33%) Frequent (79-30%) HP:0000597
10 abnormality of dental enamel 59 32 frequent (33%) Frequent (79-30%) HP:0000682
11 subcutaneous hemorrhage 59 32 hallmark (90%) Very frequent (99-80%) HP:0001933
12 fatigable weakness 59 32 occasional (7.5%) Occasional (29-5%) HP:0003473
13 abnormal pattern of respiration 59 32 frequent (33%) Frequent (79-30%) HP:0002793
14 oral leukoplakia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002745
15 milia 59 32 occasional (7.5%) Frequent (79-30%) HP:0001056
16 muscle weakness 59 Very frequent (99-80%)
17 nail dystrophy 32 occasional (7.5%) HP:0008404
18 nail dysplasia 32 occasional (7.5%) HP:0002164
19 palmoplantar hyperkeratosis 32 HP:0000972

Drugs & Therapeutics for Epidermolysis Bullosa Simplex, Generalized

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

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

Genetic Tests for Epidermolysis Bullosa Simplex, Generalized

Genetic tests related to Epidermolysis Bullosa Simplex, Generalized:

# Genetic test Affiliating Genes
1 Epidermolysis Bullosa Simplex, Koebner Type 29 KRT14 KRT5

Anatomical Context for Epidermolysis Bullosa Simplex, Generalized

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

41
Skin, Breast, Tonsil

Publications for Epidermolysis Bullosa Simplex, Generalized

Articles related to Epidermolysis Bullosa Simplex, Generalized:

# Title Authors Year
1
Epidermolysis bullosa simplex generalized severe induces a Th17 response and is improved by Apremilast treatment. ( 29932457 )
2018
2
Epidermolysis bullosa simplex-generalized severe type due to keratin 5 p.Glu477Lys mutation: Genotype-phenotype correlation and in silico modeling analysis. ( 30515866 )
2018
3
A Sporadic Neonatal Case of Epidermolysis Bullosa Simplex Generalized Intermediate with KRT5 and KRT14 Gene Mutations. ( 26929861 )
2016
4
The first familial cases of epidermolysis bullosa simplex, generalized severe with p.Asn176Ser in KRT5 revealing the clinical chronology. ( 27868258 )
2016
5
Kaposi varicelliform eruption in a patient with epidermolysis bullosa simplex generalized severe. ( 27284571 )
2016
6
In-frame Exon Skipping in KRT5 due to Novel Intronic Deletion Causes Epidermolysis Bullosa Simplex, Generalized Severe. ( 27136972 )
2016
7
Oral erythromycin therapy in epidermolysis bullosa simplex generalized severe. ( 25601422 )
2015
8
Exome sequencing reveals a novel mutation, p.L325H, in the KRT5 gene associated with autosomal dominant Epidermolysis Bullosa Simplex Koebner type in a large family from western India. ( 27081501 )
2014
9
Missense mutation at the helix termination region in the 2B domain of keratin 14 in a Japanese family with epidermolysis bullosa simplex, generalized, other. ( 21413954 )
2011
10
Autosomal recessive epidermolysis bullosa simplex. Generalized phenotypic features suggestive of junctional or dystrophic epidermolysis bullosa, and association with neuromuscular diseases. ( 2662909 )
1989

Variations for Epidermolysis Bullosa Simplex, Generalized

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

75 (show all 20)
# Symbol AA change Variation ID SNP ID
1 KRT14 p.Met272Arg VAR_003841 rs61371557
2 KRT14 p.Leu384Pro VAR_003843 rs59629244
3 KRT14 p.Tyr415His VAR_003844 rs58380626
4 KRT14 p.Leu122Phe VAR_010442 rs59110575
5 KRT14 p.Leu143Pro VAR_010446 rs61326242
6 KRT14 p.Ala247Asp VAR_010447 rs147611635
7 KRT14 p.Met119Val VAR_023719 rs61263401
8 KRT14 p.Val133Leu VAR_023723 rs61027685
9 KRT14 p.Ala413Thr VAR_023725 rs59780231
10 KRT14 p.Met272Thr VAR_027719 rs61371557
11 KRT14 p.Arg134Pro VAR_031635 rs61540016
12 KRT5 p.Leu463Pro VAR_003876 rs57599352
13 KRT5 p.Lys173Asn VAR_010455 rs58163069
14 KRT5 p.Val323Ala VAR_010460 rs59840738
15 KRT5 p.Leu325Pro VAR_010461 rs58107458
16 KRT5 p.Val186Leu VAR_013829 rs121912475
17 KRT5 p.Val143Asp VAR_031640 rs59851104
18 KRT5 p.Val186Met VAR_031642 rs121912475
19 KRT5 p.Gln191Pro VAR_031643 rs57751134
20 KRT5 p.Gly517Asp VAR_031645 rs58608695

ClinVar genetic disease variations for Epidermolysis Bullosa Simplex, Generalized:

6 (show all 22)
# Gene Variation Type Significance SNP ID Assembly Location
1 KRT14 NM_000526.4(KRT14): c.1151T> C (p.Leu384Pro) single nucleotide variant Pathogenic rs59629244 GRCh37 Chromosome 17, 39739610: 39739610
2 KRT14 NM_000526.4(KRT14): c.1151T> C (p.Leu384Pro) single nucleotide variant Pathogenic rs59629244 GRCh38 Chromosome 17, 41583358: 41583358
3 KRT14 NM_000526.4(KRT14): c.815T> G (p.Met272Arg) single nucleotide variant Pathogenic rs61371557 GRCh37 Chromosome 17, 39740124: 39740124
4 KRT14 NM_000526.4(KRT14): c.815T> G (p.Met272Arg) single nucleotide variant Pathogenic rs61371557 GRCh38 Chromosome 17, 41583872: 41583872
5 KRT5 NM_000424.3(KRT5): c.1388T> C (p.Leu463Pro) single nucleotide variant Pathogenic rs57599352 GRCh37 Chromosome 12, 52910472: 52910472
6 KRT5 NM_000424.3(KRT5): c.1388T> C (p.Leu463Pro) single nucleotide variant Pathogenic rs57599352 GRCh38 Chromosome 12, 52516688: 52516688
7 KRT5 NM_000424.3(KRT5): c.519G> C (p.Lys173Asn) single nucleotide variant Pathogenic rs58163069 GRCh37 Chromosome 12, 52913562: 52913562
8 KRT5 NM_000424.3(KRT5): c.519G> C (p.Lys173Asn) single nucleotide variant Pathogenic rs58163069 GRCh38 Chromosome 12, 52519778: 52519778
9 KRT5 NM_000424.3(KRT5): c.20T> C (p.Val7Ala) single nucleotide variant Pathogenic rs121912474 GRCh37 Chromosome 12, 52914061: 52914061
10 KRT5 NM_000424.3(KRT5): c.20T> C (p.Val7Ala) single nucleotide variant Pathogenic rs121912474 GRCh38 Chromosome 12, 52520277: 52520277
11 KRT5 NM_000424.3(KRT5): c.556G> T (p.Val186Leu) single nucleotide variant Pathogenic rs121912475 GRCh37 Chromosome 12, 52912944: 52912944
12 KRT5 NM_000424.3(KRT5): c.556G> T (p.Val186Leu) single nucleotide variant Pathogenic rs121912475 GRCh38 Chromosome 12, 52519160: 52519160
13 KLHL24 NM_017644.3(KLHL24): c.3G> A (p.Met1Ile) single nucleotide variant Pathogenic rs886037957 GRCh37 Chromosome 3, 183368147: 183368147
14 KLHL24 NM_017644.3(KLHL24): c.3G> A (p.Met1Ile) single nucleotide variant Pathogenic rs886037957 GRCh38 Chromosome 3, 183650359: 183650359
15 KLHL24 NM_017644.3(KLHL24): c.3G> T (p.Met1Ile) single nucleotide variant Pathogenic rs886037957 GRCh37 Chromosome 3, 183368147: 183368147
16 KLHL24 NM_017644.3(KLHL24): c.3G> T (p.Met1Ile) single nucleotide variant Pathogenic rs886037957 GRCh38 Chromosome 3, 183650359: 183650359
17 KLHL24 NM_017644.3(KLHL24): c.1A> G (p.Met1Val) single nucleotide variant Pathogenic rs886037956 GRCh37 Chromosome 3, 183368145: 183368145
18 KLHL24 NM_017644.3(KLHL24): c.1A> G (p.Met1Val) single nucleotide variant Pathogenic rs886037956 GRCh38 Chromosome 3, 183650357: 183650357
19 KLHL24 NM_017644.3(KLHL24): c.2T> C (p.Met1Thr) single nucleotide variant Pathogenic rs1057515580 GRCh37 Chromosome 3, 183368146: 183368146
20 KLHL24 NM_017644.3(KLHL24): c.2T> C (p.Met1Thr) single nucleotide variant Pathogenic rs1057515580 GRCh38 Chromosome 3, 183650358: 183650358
21 KRT5 NM_000424.3(KRT5): c.1394T> G (p.Val465Gly) single nucleotide variant Likely pathogenic GRCh38 Chromosome 12, 52516682: 52516682
22 KRT5 NM_000424.3(KRT5): c.1394T> G (p.Val465Gly) single nucleotide variant Likely pathogenic GRCh37 Chromosome 12, 52910466: 52910466

Expression for Epidermolysis Bullosa Simplex, Generalized

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

Pathways for Epidermolysis Bullosa Simplex, Generalized

Pathways related to Epidermolysis Bullosa Simplex, Generalized 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, Generalized

Cellular components related to Epidermolysis Bullosa Simplex, Generalized 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, Generalized 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 8.62 KRT14 KRT5

Molecular functions related to Epidermolysis Bullosa Simplex, Generalized 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, Generalized

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