MCID: EPD001
MIFTS: 52

Epidermodysplasia Verruciformis

Categories: Genetic diseases, Rare diseases, Skin diseases, Blood diseases

Aliases & Classifications for Epidermodysplasia Verruciformis

MalaCards integrated aliases for Epidermodysplasia Verruciformis:

Name: Epidermodysplasia Verruciformis 53 12 72 49 55 71 36 28 13 51 41 14 69
Lutz-Lewandowsky Epidermodysplasia Verruciformis 49 55
Lewandowsky-Lutz Syndrome 49 55
Ev 53 71

Characteristics:

Orphanet epidemiological data:

55
epidermodysplasia verruciformis
Inheritance: Autosomal recessive; Age of onset: All ages; Age of death: normal life expectancy;

OMIM:

53
Inheritance:
? autosomal recessive predisposition to viral etiology


Classifications:



External Ids:

OMIM 53 226400
Disease Ontology 12 DOID:13777
MeSH 41 D004819
SNOMED-CT 64 19138001
Orphanet 55 ORPHA302
MESH via Orphanet 42 D004819
UMLS via Orphanet 70 C0014522
ICD10 via Orphanet 33 B07
MedGen 39 C0014522
KEGG 36 H00842
UMLS 69 C0014522

Summaries for Epidermodysplasia Verruciformis

NIH Rare Diseases : 49 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 302Disease definitionEpidermodysplasia verruciformis (EV) is a rare inherited genodermatosis characterized by chronic infection with human papillomavirus (HPV) leading to polymorphous cutaneous lesions and high risk of developing non melanoma skin cancer.EpidemiologyThe exact prevalence of EV is unknown; more than 200 cases have been reported in the literature so far.Clinical descriptionThe disease usually manifests during infancy (7.5% of cases), childhood (61.5% of cases) or puberty (22% of cases) with a progressive development of hyperpigmented or hypopigmented flat wart-like papules, irregular reddish brown plaques, seborrheic keratosis-like lesions and pityriasis versicolor-like macules on the trunk, neck, face, dorsal hands and feet (sun-exposed skin). Various HPV subtypes (HPV5 and HPV8 are found in 80% of cases) can be detected in the cutaneous lesions. Thirty to 60% of patients develop non-melanoma skin cancers, especially squamous cell carcinomas (SCC), during the fourth or fifth decades of life, mainly on sun-exposed areas. Black-skinned patients have a much lower incidence of skin cancer. Most SCC remain local; metastases are uncommon.EtiologyEV can be caused by loss-of-function mutations in either of the 2 adjacent genesEVER1/TMC6 or EVER2/TMC8 (17q25.3) coding for membrane proteins that form a complex with the Zinc transporter protein ZnT-1 in the endoplasmic reticulum (ER) membrane of keratinocytes. The mutations in these genes lead to susceptibility to infection with specific HPV subtypes belonging to the beta genus, including HPV5, 8, 9, 12, 14, 15, 17, 19-25, 36-38, 47 and 49, which are ubiquitous and harmless to healthy individuals.Diagnostic methodsDiagnosis is based on clinical and histological findings. Skin biopsy shows verruca plana-like lesions with mild hyperkeratosis, hypergranulosis and acanthosis of the epidermis. Keratinocytes of the upper epidermal layers are enlarged with perinuclear vacuolization and a typical blue-gray pallor. HPVs can be detected in keratinocytes using in situ hybridization or immunohistochemistry with anti-HPV antibodies.Differential diagnosisDifferential diagnosis includes squamous cell carcinoma, acrokeratosis verruciformis (see these terms), tinea versicolor, and generalized verrucosis of other origin. In addition, an acquired epidermodysplasia verruciformis-like syndrome has been described in patients with impaired cell-mediated immunity, mainly HIV-infected subjects.Genetic counselingIn most cases, transmission is autosomal recessive but sex-linked and autosomal dominant inheritance patterns have also been reported.Management and treatmentAlthough permanent cure of EV cannot be achieved by any therapy at present, described treatment modalities include cryotherapy, topical imiquimod and 5-fluorouracil, systemic retinoids, interferon alpha, and 5-aminolevulinic acid photodynamic therapy. Surgical excision is the treatment of choice for SCC. Preventive measures, in particular sun exposure avoidance and photoprotection, are crucial for proper management.PrognosisPrognosis is favorable since skin tumors appear progressively and metastases are uncommon.Visit the Orphanet disease page for more resources. Last updated: 2/4/2010

MalaCards based summary : Epidermodysplasia Verruciformis, also known as lutz-lewandowsky epidermodysplasia verruciformis, is related to molluscum contagiosum and acanthoma, and has symptoms including lesions on the body, hypopigmented skin patches and telangiectasia of the skin. An important gene associated with Epidermodysplasia Verruciformis is TMC8 (Transmembrane Channel Like 8), and among its related pathways/superpathways is Keratinization. The drugs Glycolic acid and Ethanol have been mentioned in the context of this disorder. Affiliated tissues include skin, skin and t cells.

OMIM : 53 Epidermodysplasia verruciformis (EV) is a rare genodermatosis associated with a high risk of skin cancer (Ramoz et al., 2000). EV results from an abnormal susceptibility to specific related human papillomavirus (HPV) genotypes and to the oncogenic potential of some of them, mainly HPV5. Infection with EV-associated HPV leads to the early development of disseminated flat wart-like and pityriasis versicolor-like lesions. Patients are unable to reject their lesions, and cutaneous Bowen carcinomas in situ and invasive squamous cell carcinomas develop in about half of them, mainly on sun-exposed areas. (226400)

UniProtKB/Swiss-Prot : 71 Epidermodysplasia verruciformis: Rare autosomal recessive genodermatosis associated with a high risk of skin carcinoma that results from an abnormal susceptibility to infection by specific human papillomaviruses. Infection leads to persistent wart-like or macular lesions.

Disease Ontology : 12 An autosomal recessive disease that results_in skin squamous cell carcinoma located in skin, associated with a high risk of carcinoma. It is characterized by abnormal susceptibility to human papillomaviruses of the skin and has symptom lesions on the body.

Wikipedia : 72 Epidermodysplasia verruciformis (EV), also known as treeman syndrome, is an extremely rare autosomal... more...

Related Diseases for Epidermodysplasia Verruciformis

Diseases related to Epidermodysplasia Verruciformis via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 108)
# Related Disease Score Top Affiliating Genes
1 molluscum contagiosum 30.3 CORO1A FLG
2 acanthoma 30.0 KRT1 KRT10
3 keratosis 29.9 FLG KRT1 KRT10
4 papilloma 29.6 FLG KRT1 KRT10 KRT14
5 keratoacanthoma 29.4 FLG KRT10
6 ichthyosis 29.1 FLG KRT1 KRT10
7 psoriasis 28.6 FLG KRT1 KRT10 KRT14 TNF
8 epidermodysplasia verruciformis, x-linked 12.2
9 t-cell immunodeficiency with epidermodysplasia verruciformis 12.2
10 squamous cell carcinoma 10.6
11 pityriasis versicolor 10.5 TMC6 TMC8
12 superficial mycosis 10.5 TMC6 TMC8
13 lymphoma 10.4
14 bowen's disease 10.3
15 basal cell carcinoma, infundibulocystic 10.3 KRT10 KRT14
16 large cell acanthoma 10.3 KRT10 KRT14
17 mucositis 10.3
18 epidermolysis bullosa simplex with mottled pigmentation 10.3 KRT10 KRT14
19 breast squamous cell carcinoma 10.3 KRT10 KRT14
20 systemic lupus erythematosus 10.2
21 melanoma 10.2
22 merkel cell carcinoma 10.2
23 pustulosis of palm and sole 10.2
24 lupus erythematosus 10.2
25 epidermolysis bullosa simplex, dowling-meara type 10.2 KRT10 KRT14
26 leprosy 3 10.2
27 breast metaplastic carcinoma 10.2 KRT10 KRT14
28 intraneural perineurioma 10.1 KRT10 KRT14
29 lichen sclerosus 10.1 ECM1 TNF
30 discoid lupus erythematosus 10.1 FLG KRT10
31 combined immunodeficiency, x-linked 10.1
32 b-cell expansion with nfkb and t-cell anergy 10.1
33 common variable immunodeficiency 10.1
34 hepatitis 10.1
35 hepatitis b 10.1
36 leukemia 10.1
37 tuberculoid leprosy 10.1
38 cervicitis 10.1
39 rhabdomyosarcoma 10.1
40 pinguecula 10.1 KRT10 KRT14
41 ichthyosis, x-linked 10.1 FLG KRT10
42 sweat gland disease 10.1 KRT14 TNF
43 erythroderma, ichthyosiform, congenital reticular 10.0 KRT1 KRT10
44 asthma 10.0
45 epidermolytic acanthoma 10.0 KRT1 KRT10
46 irritant dermatitis 9.9 FLG TNF
47 ichthyosis, cyclic, with epidermolytic hyperkeratosis 9.9 KRT1 KRT10
48 acrokeratosis verruciformis 9.9
49 hepatocellular carcinoma 9.9
50 neurofibromatosis, type iv, of riccardi 9.9

Graphical network of the top 20 diseases related to Epidermodysplasia Verruciformis:



Diseases related to Epidermodysplasia Verruciformis

Symptoms & Phenotypes for Epidermodysplasia Verruciformis

Symptoms via clinical synopsis from OMIM:

53
Skin:
basal cell carcinoma
epidermodysplasia verruciformis
verrucae planae

Lab:
epidermal cell vacuolization


Clinical features from OMIM:

226400

Symptoms:

12
  • lesions on the body

Human phenotypes related to Epidermodysplasia Verruciformis:

55 31 (show all 13)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypopigmented skin patches 55 31 frequent (33%) Frequent (79-30%) HP:0001053
2 telangiectasia of the skin 55 31 occasional (7.5%) Occasional (29-5%) HP:0100585
3 multiple cafe-au-lait spots 55 31 frequent (33%) Frequent (79-30%) HP:0007565
4 seborrheic dermatitis 55 31 hallmark (90%) Very frequent (99-80%) HP:0001051
5 papule 55 31 hallmark (90%) Very frequent (99-80%) HP:0200034
6 recurrent skin infections 55 31 hallmark (90%) Very frequent (99-80%) HP:0001581
7 verrucae 55 31 hallmark (90%) Very frequent (99-80%) HP:0200043
8 squamous cell carcinoma 55 31 occasional (7.5%) Occasional (29-5%) HP:0002860
9 pustule 55 31 hallmark (90%) Very frequent (99-80%) HP:0200039
10 skin plaque 55 31 hallmark (90%) Very frequent (99-80%) HP:0200035
11 abnormality of metabolism/homeostasis 31 HP:0001939
12 abnormality of the immune system 55 Very frequent (99-80%)
13 basal cell carcinoma 31 HP:0002671

Drugs & Therapeutics for Epidermodysplasia Verruciformis

Drugs for Epidermodysplasia Verruciformis (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 8)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Glycolic acid Approved, Investigational 79-14-1 757
2
Ethanol Approved 64-17-5 702
3 Dermatologic Agents
4 Keratolytic Agents
5 Anti-Infective Agents
6 Anti-Infective Agents, Local
7 Central Nervous System Depressants
8 Pharmaceutical Solutions

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Acquired Epidermodysplasia Verruciformis (EV) Syndrome in HIV-infected Pediatric Patients Completed NCT01289171 Glycolic acid
2 Evaluation of the Effectiveness of an Alcohol Based Hand Gel for the Reduction of Warts on the Hands Completed NCT00973856

Search NIH Clinical Center for Epidermodysplasia Verruciformis

Cochrane evidence based reviews: epidermodysplasia verruciformis

Genetic Tests for Epidermodysplasia Verruciformis

Genetic tests related to Epidermodysplasia Verruciformis:

# Genetic test Affiliating Genes
1 Epidermodysplasia Verruciformis 28 TMC6 TMC8

Anatomical Context for Epidermodysplasia Verruciformis

The Foundational Model of Anatomy Ontology organs/tissues related to Epidermodysplasia Verruciformis:

18
Skin

MalaCards organs/tissues related to Epidermodysplasia Verruciformis:

38
Skin, T Cells, Brain, Testes, Eye, Myeloid, B Cells

Publications for Epidermodysplasia Verruciformis

Articles related to Epidermodysplasia Verruciformis:

(show top 50) (show all 405)
# Title Authors Year
1
Epidermodysplasia verruciformis in an adult patient with a germline Interleukin-2 inducible T-Cell Kinase mutation and lymphoma: the case of inherited versus acquired. ( 29237091 )
2017
2
A novel homozygous DOCK8 mutation associated with unusual coexistence of gross molluscum contagiosum and epidermodysplasia verruciformis in a DOCK8 deficiency patient. ( 28670845 )
2017
3
Perianal Epidermodysplasia Verruciformis Associated With Human Papillomavirus 5 After a Renal Transplant. ( 28504981 )
2017
4
Eccrine Syringofibroadenoma in Association With Acquired Epidermodysplasia Verruciformis. ( 28346303 )
2017
5
Epidermodysplasia Verruciformis-like HPV infection of the Vulva in Immunosuppressed Women. ( 28700430 )
2017
6
Novel TMC8 splice site mutation in epidermodysplasia verruciformis and review of HPV infections in patients with the disease. ( 28646613 )
2017
7
Acquired Epidermodysplasia Verruciformis and Its Relationship to Immunosuppressive Therapy: Report of a Case and Review of the Literature. ( 28697224 )
2017
8
Case of diffuse panbronchiolitis developed in a patient with epidermodysplasia verruciformis. ( 28836693 )
2017
9
Acquired epidermodysplasia verruciformis occurring in a renal transplant recipient. ( 28632809 )
2017
10
Combined immunodeficiency with EBV positive B cell lymphoma and epidermodysplasia verruciformis due to a novel homozygous mutation in RASGRP1. ( 28822832 )
2017
11
Re-evaluation of epidermodysplasia verruciformis: Reconciling more than 90A years of debate. ( 28196644 )
2017
12
Benign and malignant hybrid adnexal tumors in a patient with epidermodysplasia verruciformis. ( 28796338 )
2017
13
Comparative study of p16 protein expression in squamous cell carcinomas from patients with epidermodysplasia verruciformis and patients without the disease. ( 28439661 )
2017
14
A case of acquired epidermodysplasia verruciformis in a renal transplant recipient clearing with multimodal treatment including HPV (Gardasil) vaccination. ( 28718200 )
2017
15
Epidermodysplasia verruciformis: three case reports and a brief review. ( 28941263 )
2017
16
Epidermodysplasia verruciformis as a manifestation of ARTEMIS deficiency in a young adult. ( 27568080 )
2016
17
Epidermodysplasia verruciformis-related human papillomavirus 76 was isolated from plantar warts of a healthy individual. ( 26775884 )
2016
18
Acrokeratosis Verruciformis of Hopf Clinically Mimicking Epidermodysplasia Verruciformis. ( 27057054 )
2016
19
Expanding genetics and phenotypic spectrum of epidermodysplasia verruciformis. ( 27996151 )
2016
20
Acquired epidermodysplasia verruciformis associated with human papillomavirus type 47 in a HIV-infected patient. ( 26778636 )
2016
21
Identification of the LCK mutation in an atypical epidermodysplasia verruciformis family with T cell defects and virus-induced squamous cell carcinoma. ( 27087313 )
2016
22
Epidermodysplasia verruciformis and the risk for malignancy. ( 27874888 )
2016
23
Sebaceous cell carcinoma developing in epidermodysplasia verruciformis. ( 27279310 )
2016
24
Treatment of Imiquimod Resistant Epidermodysplasia Verruciformis With Ingenol Mebutate. ( 26954321 )
2016
25
Sebaceous cell carcinoma developing in epidermodysplasia verruciformis. ( 26858060 )
2016
26
The EVER genes - the genetic etiology of carcinogenesis in epidermodysplasia verruciformis and a possible role in non-epidermodysplasia verruciformis patients. ( 27279814 )
2016
27
Acquired Epidermodysplasia Verruciformis Associated with Human Papilloma Virus Type 14 in a Small Bowel Transplanted Child--A Case Report. ( 26646304 )
2016
28
Acquired epidermodysplasia verruciformis in an HIV-positive patient. ( 26516132 )
2015
29
Acquired epidermodysplasia verruciformis, a new opportunistic infection related to bendamustine. ( 25677268 )
2015
30
Bilateral recurrent ocular surface squamous cell cancer associated with epidermodysplasia verruciformis. ( 25636630 )
2015
31
Epidermodysplasia verruciformis: successful treatment with squaric acid dibutylester. ( 26367749 )
2015
32
Cornoid Lamella-Like Structures in HIV-Associated Epidermodysplasia Verruciformis: A Unique Histopathologic Finding. ( 26588337 )
2015
33
Remission of an epidermodysplasia verruciformis-like eruption in an HIV-positive man long after immune restoration. ( 26243233 )
2015
34
Adult T-cell Lymphoma Complicated with Epidermodysplasia Verruciformis-like Eruptions. ( 26724886 )
2015
35
Possible association between actinic keratosis and the rs7208422 (c.917Aa89T, p.N306l) polymorphism of the EVER2 gene in patients without epidermodysplasia verruciformis. ( 25495765 )
2015
36
Genetic variations in the epidermodysplasia verruciformis (EVER/TMC) genes, cutaneous human papillomavirus infection and squamous cell carcinoma of the skin. ( 26126409 )
2015
37
Deleterious Effect of Radiation Therapy on Epidermodysplasia Verruciformis Patients. ( 26156649 )
2015
38
Efficacy of oral zinc therapy in epidermodysplasia verruciformis with squamous cell carcinoma. ( 24616858 )
2014
39
The transmembrane channel-like protein family and human papillomaviruses: Insights into epidermodysplasia verruciformis and progression to squamous cell carcinoma. ( 24800179 )
2014
40
Human immunodeficiency virus (HIV)-associated epidermodysplasia verruciformis eradicated after interferon-I+ and ribavirin treatment. ( 24527965 )
2014
41
Two sisters reveal autosomal recessive inheritance of epidermodysplasia verruciformis: a case report. ( 25048734 )
2014
42
Acquired epidermodysplasia verruciformis in a renal transplant recipient--case report. ( 24626660 )
2014
43
Palliative effect of capecitabine and cetuximab for refractory metastatic squamous cell carcinoma of the perineum in epidermodysplasia verruciformis. ( 24720087 )
2014
44
Characterization of skin lesions induced by skin-tropic I+- and I^-papillomaviruses in a patient with epidermodysplasia verruciformis. ( 24902472 )
2014
45
Acquired epidermodysplasia verruciformis in an HIV-infected patient. ( 24581031 )
2014
46
Expression of the epidermodysplasia verruciformis-associated genes EVER1 and EVER2 is activated by exogenous DNA and inhibited by LMP1 oncoprotein from Epstein-Barr virus. ( 25378492 )
2014
47
Epidermodysplasia Verruciformis-like Skin Eruption in an HIV-positive Patient. ( 25589883 )
2014
48
Brazilian waxing and human papillomavirus: a case of acquired epidermodysplasia verruciformis. ( 25183723 )
2014
49
Compound heterozygous CORO1A mutations in siblings with a mucocutaneous-immunodeficiency syndrome of epidermodysplasia verruciformis-HPV, molluscum contagiosum and granulomatous tuberculoid leprosy. ( 25073507 )
2014
50
Spontaneous regression of Merkel cell carcinoma developed in a patient with epidermodysplasia verruciformis. ( 24985741 )
2014

Variations for Epidermodysplasia Verruciformis

ClinVar genetic disease variations for Epidermodysplasia Verruciformis:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 TMC8 TMC8, 1-BP DEL, 754T deletion Pathogenic
2 TMC8 NM_152468.4(TMC8): c.1084G> T (p.Glu362Ter) single nucleotide variant Pathogenic rs121908330 GRCh37 Chromosome 17, 76131047: 76131047
3 TMC6 NM_007267.7(TMC6): c.280C> T (p.Arg94Ter) single nucleotide variant Pathogenic rs121908327 GRCh37 Chromosome 17, 76121957: 76121957
4 TMC6 NM_007267.7(TMC6): c.1726G> T (p.Glu576Ter) single nucleotide variant Pathogenic rs121908328 GRCh37 Chromosome 17, 76115463: 76115463
5 TMC6 NM_007267.7(TMC6): c.744C> A (p.Tyr248Ter) single nucleotide variant Pathogenic rs121908329 GRCh37 Chromosome 17, 76120752: 76120752
6 TMC6 NM_007267.7(TMC6): c.892-2A> T single nucleotide variant Pathogenic rs769471844 GRCh37 Chromosome 17, 76120262: 76120262
7 TMC8 NC_000017.11: g.(?_78137697)_(78137834_?)del deletion Pathogenic GRCh38 Chromosome 17, 78137697: 78137834

Expression for Epidermodysplasia Verruciformis

Search GEO for disease gene expression data for Epidermodysplasia Verruciformis.

Pathways for Epidermodysplasia Verruciformis

Pathways related to Epidermodysplasia Verruciformis according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.38 FLG KRT1 KRT10 KRT14

GO Terms for Epidermodysplasia Verruciformis

Cellular components related to Epidermodysplasia Verruciformis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular exosome GO:0070062 9.76 CORO1A ECM1 KRT1 KRT10 KRT14 LCK
2 immunological synapse GO:0001772 9.32 CORO1A LCK
3 phagocytic cup GO:0001891 9.26 CORO1A TNF
4 cornified envelope GO:0001533 9.13 FLG KRT1 KRT10
5 intermediate filament GO:0005882 8.92 FLG KRT1 KRT10 KRT14

Biological processes related to Epidermodysplasia Verruciformis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 keratinization GO:0031424 9.5 KRT1 KRT10 KRT14
2 positive regulation of T cell activation GO:0050870 9.26 CORO1A LCK
3 establishment of skin barrier GO:0061436 9.16 FLG KRT1
4 peptide cross-linking GO:0018149 9.13 FLG KRT1 KRT10
5 cornification GO:0070268 8.92 FLG KRT1 KRT10 KRT14

Molecular functions related to Epidermodysplasia Verruciformis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein C-terminus binding GO:0008022 9.33 CORO1A ECM1 LCK
2 phosphatidylinositol 3-kinase binding GO:0043548 8.96 CORO1A LCK
3 structural constituent of epidermis GO:0030280 8.8 FLG KRT1 KRT10

Sources for Epidermodysplasia Verruciformis

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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