Full Report

Format

Full Report
Summary (Text)
Summary (XML)

Send to:

Choose Destination

File
Clipboard
Collections

Erythrokeratodermia variabilis et progressiva 3(EKVP3)

MedGen UID:: 1380593
•Concept ID:: C4479619
•: Disease or Syndrome

Synonym:	EKVP3

Gene (location): Gene(s) directly associated with this condition or phenotype.	GJA1 (6q22.31)

Monarch Initiative:	MONDO:0033013
OMIM®:	617525

Definition

Erythrokeratodermia variabilis et progressiva is a rare skin disease. Patients with EKVP3 have normal skin at birth but develop hyperpigmentation and scaling at sites of friction in childhood, with progression to near-confluent corrugated hyperkeratosis, palmoplantar keratoderma, and transient figurate erythema (summary by Boyden et al., 2015). For a discussion of genetic heterogeneity of EKVP, see EKVP1 (133200). [from OMIM]

Clinical features

From HPO

Palmoplantar keratoderma

MedGen UID:: 1635750
•Concept ID:: C4551675
•: Disease or Syndrome

Abnormal thickening of the skin of the palms of the hands and the soles of the feet.

See: Feature record | Search on this feature

Erythema

MedGen UID:: 11999
•Concept ID:: C0041834
•: Disease or Syndrome

Redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin.

See: Feature record | Search on this feature

Epidermal acanthosis

MedGen UID:: 65136
•Concept ID:: C0221270
•: Finding

Diffuse hypertrophy or thickening of the stratum spinosum of the epidermis (prickle cell layer of the skin).

See: Feature record | Search on this feature

Leukonychia

MedGen UID:: 68698
•Concept ID:: C0240182
•: Finding

White discoloration of the nails.

See: Feature record | Search on this feature

Hyperkeratosis

MedGen UID:: 209030
•Concept ID:: C0870082
•: Disease or Syndrome

Hyperkeratosis is thickening of the outer layer of the skin, the stratum corneum, which is composed of large, polyhedral, plate-like envelopes filled with keratin which are the dead cells that have migrated up from the stratum granulosum.

See: Feature record | Search on this feature

Orthokeratosis

MedGen UID:: 375169
•Concept ID:: C1843359
•: Finding

Formation of an anuclear keratin layer

See: Feature record | Search on this feature

Hypergranulosis

MedGen UID:: 481177
•Concept ID:: C3279547
•: Finding

Hypergranulosis is an increased thickness of the stratum granulosum.

See: Feature record | Search on this feature

Show all Hide all

Abnormality of limbs
- Palmoplantar keratoderma
Abnormality of the integument

Professional guidelines

PubMed

Genetic heterogeneity in erythrokeratodermia variabilis: novel mutations in the connexin gene GJB4 (Cx30.3) and genotype-phenotype correlations.

Richard G, Brown N, Rouan F, Van der Schroeff JG, Bijlsma E, Eichenfield LF, Sybert VP, Greer KE, Hogan P, Campanelli C, Compton JG, Bale SJ, DiGiovanna JJ, Uitto J
J Invest Dermatol 2003 Apr;120(4):601-9. doi: 10.1046/j.1523-1747.2003.12080.x. PMID: 12648223

See all (1)

Recent clinical studies

Etiology

Erythrokeratodermia Variabilis-like Phenotype in Patients Carrying ABCA12 Mutations.

Hotz A, Fölster-Holst R, Oji V, Bourrat E, Frank J, Marrakchi S, Ennouri M, Wankner L, Komlosi K, Alter S, Fischer J
Genes (Basel) 2024 Feb 24;15(3) doi: 10.3390/genes15030288. PMID: 38540347 Free PMC Article

The Role of Desmoglein 1 in Gap Junction Turnover Revealed through the Study of SAM Syndrome.

Cohen-Barak E, Godsel LM, Koetsier JL, Hegazy M, Kushnir-Grinbaum D, Hammad H, Danial-Farran N, Harmon R, Khayat M, Bochner R, Peled A, Rozenblat M, Krausz J, Sarig O, Johnson JL, Ziv M, Shalev SA, Sprecher E, Green KJ
J Invest Dermatol 2020 Mar;140(3):556-567.e9. Epub 2019 Aug 26 doi: 10.1016/j.jid.2019.08.433. PMID: 31465738 Free PMC Article

Familial erythrokeratodermia variabilis with pustular lesions: a new variant?

Zhang L, Huo W, Gao XH, Ma L, Xiu Y, Zheng S, Hong Y, Chen HD
Acta Derm Venereol 2010 May;90(3):274-8. doi: 10.2340/00015555-0821. PMID: 20526545

Genetic linkage between erythrokeratodermia variabilis and Rh locus.

van der Schroeff JG, Nijenhuis LE, Meera Khan P, Bernini LF, Schreuder GM, van Loghem E, Volkers WS, Went LN
Hum Genet 1984;68(2):165-8. doi: 10.1007/BF00279308. PMID: 6437964

Erythrokeratodermia variabilis.

Maekawa Y, Yasaka S
J Dermatol 1977 Aug;4(4):147-50. doi: 10.1111/j.1346-8138.1977.tb01028.x. PMID: 15461342

See all (8)

Diagnosis

Erythrokeratodermia Variabilis-like Phenotype in Patients Carrying ABCA12 Mutations.

Annular Epidermolytic Ichthyosis Mimicking Greither Disease: A Case Report and Literature Review.

Almuqarrab FJ, Alakloby OM, Alqahtani JM, Hennies HC
Am J Case Rep 2022 Feb 24;23:e935393. doi: 10.12659/AJCR.935393. PMID: 35202349 Free PMC Article

Recessive mosaicism in ABCA12 causes blaschkoid congenital ichthyosiform erythroderma.

van Leersum FS, Seyger MMB, Theunissen TEJ, Bongers EMHF, Steijlen PM, van Geel M
Br J Dermatol 2020 Jan;182(1):208-211. Epub 2019 Jul 28 doi: 10.1111/bjd.18216. PMID: 31206590

Pathogenic Cx31 is un/misfolded to cause skin abnormality via a Fos/JunB-mediated mechanism.

Tang C, Chen X, Chi J, Yang D, Liu S, Liu M, Pan Q, Fan J, Wang D, Zhang Z
Hum Mol Genet 2015 Nov 1;24(21):6054-65. Epub 2015 Aug 6 doi: 10.1093/hmg/ddv317. PMID: 26251042

Molecular genetics of hearing impairment due to mutations in gap junction genes encoding beta connexins.

Rabionet R, Gasparini P, Estivill X
Hum Mutat 2000 Sep;16(3):190-202. doi: 10.1002/1098-1004(200009)16:3<190::AID-HUMU2>3.0.CO;2-I. PMID: 10980526

See all (11)

Therapy

Erythrokeratodermia variabilis et progressiva.

Ishida-Yamamoto A
J Dermatol 2016 Mar;43(3):280-5. doi: 10.1111/1346-8138.13220. PMID: 26945536

Familial erythrokeratodermia variabilis with pustular lesions: a new variant?

Zhang L, Huo W, Gao XH, Ma L, Xiu Y, Zheng S, Hong Y, Chen HD
Acta Derm Venereol 2010 May;90(3):274-8. doi: 10.2340/00015555-0821. PMID: 20526545

Erythrokeratodermia variabilis with adult onset: report of a sporadic case unresponsive to systemic retinoids.

Erbagci Z, Tuncel AA, Deniz H
J Dermatolog Treat 2006;17(3):187-9. doi: 10.1080/09546630600696377. PMID: 16854764

A new, recurrent mutation of GJB3 (Cx31) in erythrokeratodermia variabilis.

Morley SM, White MI, Rogers M, Wasserman D, Ratajczak P, McLean WH, Richard G
Br J Dermatol 2005 Jun;152(6):1143-8. doi: 10.1111/j.1365-2133.2005.06610.x. PMID: 15948974

Is the use of Ro 10-9359 (Tigason) in children justified?

van der Rhee HJ, van Gelderen HH, Polano MK
Acta Derm Venereol 1980;60(3):274-5. PMID: 6158237

See all (6)

Prognosis

The Role of Desmoglein 1 in Gap Junction Turnover Revealed through the Study of SAM Syndrome.

Sphingolipid dysregulation due to lack of functional KDSR impairs proplatelet formation causing thrombocytopenia.

Bariana TK, Labarque V, Heremans J, Thys C, De Reys M, Greene D, Jenkins B, Grassi L, Seyres D, Burden F, Whitehorn D, Shamardina O, Papadia S, Gomez K, BioResource N, Van Geet C, Koulman A, Ouwehand WH, Ghevaert C, Frontini M, Turro E, Freson K
Haematologica 2019 May;104(5):1036-1045. Epub 2018 Nov 22 doi: 10.3324/haematol.2018.204784. PMID: 30467204 Free PMC Article

Erythrokeratodermia variabilis: report of two cases and a novel missense variant in GJB4 encoding connexin 30.3.

Kokotas H, Papagiannaki K, Grigoriadou M, Petersen MB, Katsarou A
Eur J Dermatol 2012 Mar-Apr;22(2):182-6. doi: 10.1684/ejd.2011.1617. PMID: 22266302

Familial erythrokeratodermia variabilis with pustular lesions: a new variant?

Zhang L, Huo W, Gao XH, Ma L, Xiu Y, Zheng S, Hong Y, Chen HD
Acta Derm Venereol 2010 May;90(3):274-8. doi: 10.2340/00015555-0821. PMID: 20526545

Genetic heterogeneity in erythrokeratodermia variabilis: novel mutations in the connexin gene GJB4 (Cx30.3) and genotype-phenotype correlations.

See all (8)

Clinical prediction guides

Expanding the clinical phenotype associated with NIPAL4 mutation: Study of a Tunisian consanguineous family with erythrokeratodermia variabilis-Like Autosomal Recessive Congenital Ichthyosis.

Charfeddine C, Laroussi N, Mkaouar R, Jouini R, Khayat O, Redissi A, Mosbah A, Dallali H, Chedly Debbiche A, Zaouak A, Fenniche S, Abdelhak S, Hammami-Ghorbel H
PLoS One 2021;16(10):e0258777. Epub 2021 Oct 20 doi: 10.1371/journal.pone.0258777. PMID: 34669720 Free PMC Article

Clinical variability of the GJB4:c.35G > A gene variant: a study of a large Brazilian erythrokeratodermia pedigree.

de Oliveira RTG, Christofolini DM, Criado PR, Lacaz Martins E, Kelsell D, Machado Filho CDS
Int J Dermatol 2020 Jun;59(6):722-725. Epub 2020 Apr 20 doi: 10.1111/ijd.14894. PMID: 32311086

Sphingolipid dysregulation due to lack of functional KDSR impairs proplatelet formation causing thrombocytopenia.

An atypical form of erythrokeratodermia variabilis maps to chromosome 7q22.

Saba TG, Montpetit A, Verner A, Rioux P, Hudson TJ, Drouin R, Drouin CA
Hum Genet 2005 Feb;116(3):167-71. Epub 2004 Nov 25 doi: 10.1007/s00439-004-1193-8. PMID: 15668823

Genetic heterogeneity in erythrokeratodermia variabilis: novel mutations in the connexin gene GJB4 (Cx30.3) and genotype-phenotype correlations.

See all (8)

MedGen

National Center for Biotechnology Information

Send to:

Erythrokeratodermia variabilis et progressiva 3(EKVP3)

Definition

Clinical features

Professional guidelines

PubMed

Recent clinical studies

Etiology

Diagnosis

Therapy

Prognosis

Clinical prediction guides

Supplemental Content

Table of contents

Genetic Testing Registry

Clinical resources

Practice guidelines

Molecular resources

Consumer resources

Reviews

Related information

Recent activity