K-EBS
MCID: EPD029
MIFTS: 43

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 56 52
Epidermolysis Bullosa Simplex, Koebner Type 56 52 58 73 29 13 6 39
Epidermolysis Bullosa Simplex Generalized Type 12 15
Ebs, Generalized 56 52
Generalized Epidermolysis Bullosa Simplex, Non-Dowling-Meara Type 58
Epidermolysis Bullosa Simplex, Generalized Non-Dowling-Meara 52
Epidermolysis Bullosa Simplex, Generalized Intermediate 58
Epidermolysis Bullosa Simplex Koebner Type 12
Epidermolysis Bullosa Simplex, Kobner Type 58
Generalized Ebs, Non-Dowling-Meara Type 58
Epidermolysis Bullosa Simplex Kobner 71
Epidermolysis Bullosa Simplex 2 73
Ebs, Generalized Intermediate 58
Generalized Ebs 52
Ebs Generalized 73
Ebs-K 52
K-Ebs 73
Ebs2 73

Characteristics:

Orphanet epidemiological data:

58
epidermolysis bullosa simplex, generalized intermediate
Inheritance: Autosomal dominant,Not applicable; Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;

OMIM:

56
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:

31
epidermolysis bullosa simplex, generalized:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare skin diseases


External Ids:

Disease Ontology 12 DOID:0080511
OMIM 56 131900
MeSH 43 D016110
MESH via Orphanet 44 C535961
ICD10 via Orphanet 33 Q81.0
UMLS via Orphanet 72 C0079299
Orphanet 58 ORPHA79399
MedGen 41 C0079299
UMLS 71 C0079299

Summaries for Epidermolysis Bullosa Simplex, Generalized

OMIM : 56 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 Collagen chain trimerization and Degradation of the extracellular matrix. Affiliated tissues include skin and testes, and related phenotypes are abnormal blistering of the skin and subcutaneous hemorrhage

Disease Ontology : 12 An epidermolysis bullosa simplex that is characterized by widespread blisters that appear at birth or in early infancy.

NIH Rare Diseases : 52 Epidermolysis bullosa simplex (EBS), 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. There are two major subtypes of this condition and 17 minor subtypes. The four most common types of epidermolysis bullosa simplex are EBS localized, EBS generalized intermediate, EBS with mottled pigmentation and EBS generalized severe. These four common types are caused by mutations in the EXPH5 , KRT5 , KRT14 , and TGM5 genes . This condition is usually inherited in an autosomal dominant or autosomal recessive fashion. . These conditions are diagnosed based on the symptoms and by genetic testing . Treatment is focused on managing the symptoms. The symptoms of EBS tend to get better with age. The long-term outlook for people with EBS depends on how well the skin symptoms can be managed.

UniProtKB/Swiss-Prot : 73 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 top 50) (show all 85)
# Related Disease Score Top Affiliating Genes
1 epidermolysis bullosa simplex, dowling-meara type 32.0 PLEC KRT5 KRT14
2 epidermolysis bullosa simplex, localized 31.8 KRT5 KRT14
3 epidermolysis bullosa simplex with muscular dystrophy 29.9 PLEC COL17A1
4 epidermolysis bullosa dystrophica 29.4 PLEC KRT14 COL17A1
5 epidermolysis bullosa simplex 29.2 PLEC KRT5 KRT14 KLHL24 COL17A1
6 epidermolysis bullosa 28.5 PLEC LAMC2 KRT5 KRT14 KLHL24 COL17A1
7 epidermolysis bullosa simplex, generalized, with scarring and hair loss 12.9
8 epidermolysis bullosa simplex, ogna type 11.5
9 diffuse palmoplantar keratoderma 10.2 KRT5 KLHL24
10 aplasia cutis congenita, nonsyndromic 10.2
11 myasthenia gravis 10.2
12 helix syndrome 10.2
13 palmoplantar keratosis 10.2
14 congenital myasthenic syndrome 10.2
15 neuromuscular disease 10.2
16 eczema herpeticum 10.2
17 alopecia 10.2
18 muscular dystrophy 10.2
19 erythrokeratoderma ''en cocardes'' 10.2
20 rare genetic skin disease 10.2
21 inherited epidermolysis bullosa 10.2
22 benign breast adenomyoepithelioma 10.1 KRT5 KRT14
23 breast adenomyoepithelioma 10.1 KRT5 KRT14
24 ceruminous adenocarcinoma 10.1 KRT5 KRT14
25 breast myoepithelial neoplasm 10.1 KRT5 KRT14
26 squamous cell bile duct carcinoma 10.1 KRT5 KRT14
27 breast metaplastic carcinoma 10.1 KRT5 KRT14
28 epidermolysis bullosa simplex, autosomal recessive 1 10.1 KRT5 KRT14
29 odontoma 10.1 KRT5 KRT14
30 micronodular basal cell carcinoma 10.1 KRT5 KRT14
31 breast myoepithelial carcinoma 10.1 KRT5 KRT14
32 lipid-rich carcinoma 10.1 KRT5 KRT14
33 large cell acanthoma 10.1 KRT5 KRT14
34 eccrine acrospiroma 10.1 KRT5 KRT14
35 eccrine sweat gland neoplasm 10.1 KRT5 KRT14
36 eccrine papillary adenocarcinoma 10.1 KRT5 KRT14
37 apocrine sweat gland neoplasm 10.1 KRT5 KRT14
38 clear cell basal cell carcinoma 10.1 KRT5 KRT14
39 intraductal breast benign neoplasm 10.1 KRT5 KRT14
40 breast benign neoplasm 10.1 KRT5 KRT14
41 esophageal adenosquamous carcinoma 10.0 KRT5 KRT14
42 benign peritoneal mesothelioma 10.0 KRT5 KRT14
43 cystic basal cell carcinoma 10.0 KRT5 KRT14
44 reticulate acropigmentation of kitamura 10.0 KRT5 KRT14
45 intraductal papilloma 10.0 KRT5 KRT14
46 borst-jadassohn intraepidermal carcinoma 10.0 KRT5 KRT14
47 sweat gland benign neoplasm 10.0 KRT5 KRT14
48 sebaceous adenocarcinoma 10.0 KRT5 KRT14
49 sweat gland disease 10.0 KRT5 KRT14
50 thoracic benign neoplasm 10.0 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

Human phenotypes related to Epidermolysis Bullosa Simplex, Generalized:

58 31 (show all 20)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormal blistering of the skin 58 31 hallmark (90%) Very frequent (99-80%) HP:0008066
2 subcutaneous hemorrhage 58 31 hallmark (90%) Very frequent (99-80%) HP:0001933
3 oral leukoplakia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002745
4 hyperhidrosis 58 31 frequent (33%) Frequent (79-30%) HP:0000975
5 abnormality of the nail 58 31 frequent (33%) Frequent (79-30%) HP:0001597
6 generalized hyperkeratosis 58 31 frequent (33%) Frequent (79-30%) HP:0005595
7 palmoplantar keratoderma 58 31 frequent (33%) Frequent (79-30%) HP:0000982
8 abnormal pattern of respiration 58 31 frequent (33%) Frequent (79-30%) HP:0002793
9 ptosis 58 31 frequent (33%) Frequent (79-30%) HP:0000508
10 abnormality of dental enamel 58 31 frequent (33%) Frequent (79-30%) HP:0000682
11 ophthalmoparesis 58 31 frequent (33%) Frequent (79-30%) HP:0000597
12 milia 58 31 occasional (7.5%) Frequent (79-30%) HP:0001056
13 failure to thrive 58 31 occasional (7.5%) Occasional (29-5%) HP:0001508
14 respiratory insufficiency 58 31 occasional (7.5%) Occasional (29-5%) HP:0002093
15 fatigable weakness 58 31 occasional (7.5%) Occasional (29-5%) HP:0003473
16 nail dysplasia 31 occasional (7.5%) HP:0002164
17 nail dystrophy 31 occasional (7.5%) HP:0008404
18 muscle weakness 58 Very frequent (99-80%)
19 palmoplantar hyperkeratosis 31 HP:0000972
20 oral mucosal blisters 31 HP:0200097

Symptoms via clinical synopsis from OMIM:

56
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

Drugs & Therapeutics for Epidermolysis Bullosa Simplex, Generalized

Search Clinical Trials , 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:

40
Skin, Testes

Publications for Epidermolysis Bullosa Simplex, Generalized

Articles related to Epidermolysis Bullosa Simplex, Generalized:

(show all 36)
# Title Authors PMID Year
1
Epidermolysis bullosa simplex: a keratin 5 mutation is a fully dominant allele in epidermal cytoskeleton function. 56 6
7534039 1995
2
A mutation (Met-->Arg) in the type I keratin (K14) gene responsible for autosomal dominant epidermolysis bullosa simplex. 6 56
7682883 1993
3
Identification of a leucine-to-proline mutation in the keratin 5 gene in a family with the generalized Köbner type of epidermolysis bullosa simplex. 6 56
7686424 1993
4
Mapping of epidermolysis bullosa simplex mutation to chromosome 12. 56 6
1718160 1991
5
Epidermolysis bullosa simplex: evidence in two families for keratin gene abnormalities. 56 6
1720261 1991
6
The classification of inherited epidermolysis bullosa (EB): Report of the Third International Consensus Meeting on Diagnosis and Classification of EB. 56
18374450 2008
7
Expression of a truncated keratin 5 may contribute to severe palmar--plantar hyperkeratosis in epidermolysis bullosa simplex patients. 56
11407989 2001
8
A novel keratin 5 mutation (K5V186L) in a family with EBS-K: a conservative substitution can lead to development of different disease phenotypes. 6
11407988 2001
9
Epidermolysis Bullosa Simplex 6
20301543 1998
10
A novel mutation in the L12 domain of keratin 5 in the Köbner variant of epidermolysis bullosa simplex. 6
9740251 1998
11
Molecular genetics of epidermolysis bullosa. 56
1375393 1992
12
Mutant keratin expression in transgenic mice causes marked abnormalities resembling a human genetic skin disease. 6
1703046 1991
13
Revised clinical and laboratory criteria for subtypes of inherited epidermolysis bullosa. A consensus report by the Subcommittee on Diagnosis and Classification of the National Epidermolysis Bullosa Registry. 56
1999509 1991
14
Human nidogen gene: identification of multiple RFLP and exclusion as candidate gene in a family with epidermolysis bullosa (EBS2) with evidence for linkage to chromosome 1. 56
1977802 1990
15
Epidermolysis bullosa: evidence for linkage to genetic markers on chromosome 1 in a family with the autosomal dominant simplex form. 56
2365356 1990
16
Epidermolysis bullosa herpetiformis Dowling-Meara in a large family. 56
3372762 1988
17
Gelatinase expression in generalized epidermolysis bullosa simplex fibroblasts. 56
3016106 1986
18
Genetic linkage analysis of epidermolysis bullosa simplex, Köbner type. 56
6507503 1984
19
Generalized dominant epidermolysis bullosa simplex: decreased activity of a gelatinolytic protease in cultured fibroblasts as a phenotypic marker. 56
6315831 1983
20
Epidermolysis bullosa herpetiformis Dowling-Meara. Report of a case and pathomorphogenesis. 56
7084543 1982
21
Heritable fragile sites on human chromosomes. VI. Characterization of the fragile site at 12q13. 56
7194847 1981
22
Epidermolysis bullosa. 56
5859028 1965
23
Epidermolysis bullosa hereditaria simplex. A kindred affected in 4 generations. 56
5845447 1965
24
Advancement in management of epidermolysis bullosa. 52
27386970 2016
25
Hoarse cry in a newborn with epidermolysis bullosa simplex, generalized severe. 61
31957133 2020
26
Known and novel mutations responsible for epidermolysis bullosa simplex cases in a Chinese population. 61
31772641 2019
27
Epidermolysis bullosa simplex generalized severe induces a T helper 17 response and is improved by apremilast treatment. 61
29932457 2019
28
Epidermolysis bullosa simplex-generalized severe type due to keratin 5 p.Glu477Lys mutation: Genotype-phenotype correlation and in silico modeling analysis. 61
30515866 2019
29
The first familial cases of epidermolysis bullosa simplex, generalized severe with p.Asn176Ser in KRT5 revealing the clinical chronology. 61
27868258 2017
30
In-frame Exon Skipping in KRT5 due to Novel Intronic Deletion Causes Epidermolysis Bullosa Simplex, Generalized Severe. 61
27136972 2017
31
Kaposi varicelliform eruption in a patient with epidermolysis bullosa simplex generalized severe. 61
27284571 2016
32
A Sporadic Neonatal Case of Epidermolysis Bullosa Simplex Generalized Intermediate with KRT5 and KRT14 Gene Mutations. 61
26929861 2016
33
Oral erythromycin therapy in epidermolysis bullosa simplex generalized severe. 61
25601422 2015
34
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. 61
27081501 2014
35
Missense mutation at the helix termination region in the 2B domain of keratin 14 in a Japanese family with epidermolysis bullosa simplex, generalized, other. 61
21413954 2011
36
Autosomal recessive epidermolysis bullosa simplex. Generalized phenotypic features suggestive of junctional or dystrophic epidermolysis bullosa, and association with neuromuscular diseases. 61
2662909 1989

Variations for Epidermolysis Bullosa Simplex, Generalized

ClinVar genetic disease variations for Epidermolysis Bullosa Simplex, Generalized:

6 (show all 12) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 KRT14 NM_000526.5(KRT14):c.1151T>C (p.Leu384Pro)SNV Pathogenic 14611 rs59629244 17:39739610-39739610 17:41583358-41583358
2 KRT14 NM_000526.5(KRT14):c.815T>G (p.Met272Arg)SNV Pathogenic 14617 rs61371557 17:39740124-39740124 17:41583872-41583872
3 KRT5 NM_000424.4(KRT5):c.1388T>C (p.Leu463Pro)SNV Pathogenic 14639 rs57599352 12:52910472-52910472 12:52516688-52516688
4 KRT5 NM_000424.4(KRT5):c.980T>C (p.Met327Thr)SNV Pathogenic 14641 rs58072617 12:52911486-52911486 12:52517702-52517702
5 KRT5 NM_000424.4(KRT5):c.519G>C (p.Lys173Asn)SNV Pathogenic 14643 rs58163069 12:52913562-52913562 12:52519778-52519778
6 KRT5 NM_000424.4(KRT5):c.20T>C (p.Val7Ala)SNV Pathogenic 14646 rs121912474 12:52914061-52914061 12:52520277-52520277
7 KRT5 NM_000424.4(KRT5):c.556G>T (p.Val186Leu)SNV Pathogenic 14652 rs121912475 12:52912944-52912944 12:52519160-52519160
8 KLHL24 NM_017644.3(KLHL24):c.3G>A (p.Met1Ile)SNV Pathogenic 264646 rs886037957 3:183368147-183368147 3:183650359-183650359
9 KLHL24 NM_017644.3(KLHL24):c.3G>T (p.Met1Ile)SNV Pathogenic 264647 rs886037957 3:183368147-183368147 3:183650359-183650359
10 KLHL24 NM_017644.3(KLHL24):c.1A>G (p.Met1Val)SNV Pathogenic 264648 rs886037956 3:183368145-183368145 3:183650357-183650357
11 KLHL24 NM_017644.3(KLHL24):c.2T>C (p.Met1Thr)SNV Pathogenic 370042 rs1057515580 3:183368146-183368146 3:183650358-183650358
12 KRT5 NM_000424.4(KRT5):c.1394T>G (p.Val465Gly)SNV Likely pathogenic 438651 rs1555156076 12:52910466-52910466 12:52516682-52516682

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

73 (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

Expression for Epidermolysis Bullosa Simplex, Generalized

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

Pathways for Epidermolysis Bullosa Simplex, Generalized

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 keratin filament GO:0045095 9.26 KRT5 KRT14
2 basement membrane GO:0005604 9.16 LAMC2 COL17A1
3 intermediate filament GO:0005882 9.13 PLEC KRT5 KRT14
4 hemidesmosome GO:0030056 8.62 PLEC COL17A1

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

# Name GO ID Score Top Affiliating Genes
1 epidermis development GO:0008544 9.26 LAMC2 KRT5 KRT14 COL17A1
2 cornification GO:0070268 9.16 KRT5 KRT14
3 hemidesmosome assembly GO:0031581 9.02 PLEC LAMC2 KRT5 KRT14 COL17A1

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 8.8 PLEC KRT5 KRT14

Sources for Epidermolysis Bullosa Simplex, Generalized

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