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Epidermolysis bullosa simplex with mottled pigmentation(EBS2F)

MedGen UID:
140934
Concept ID:
C0432316
Congenital Abnormality
Synonyms: EBS with mottled pigmentation; EBS2F; EPIDERMOLYSIS BULLOSA SIMPLEX 2F, WITH MOTTLED PIGMENTATION; SPECKLED HYPERPIGMENTATION WITH PUNCTATE PALMOPLANTAR KERATOSES AND CHILDHOOD BLISTERING; Speckled hyperpigmentation, palmo-plantar punctate keratoses and childhood blistering
SNOMED CT: Epidermolysis bullosa simplex with mottled pigmentation (254180002); Simple epidermolysis bullosa with mottled pigmentation (254180002)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): KRT5 (12q13.13)
 
Monarch Initiative: MONDO:0007556
OMIM®: 131960
Orphanet: ORPHA79397

Disease characteristics

Excerpted from the GeneReview: Epidermolysis Bullosa Simplex
Epidermolysis bullosa simplex (EBS) is characterized by fragility of the skin (and mucosal epithelia in some instances) that results in non-scarring blisters and erosions caused by minor mechanical trauma. EBS is distinguished from other types of epidermolysis bullosa (EB) or non-EB skin fragility syndromes by the location of the blistering in relation to the dermal-epidermal junction. In EBS, blistering occurs within basal keratinocytes. The severity of blistering ranges from limited to hands and feet to widespread involvement. Additional features can include hyperkeratosis of the palms and soles (keratoderma), nail dystrophy, milia, and hyper- and/or hypopigmentation. Rare EBS subtypes have been associated with additional clinical features including pyloric atresia, muscular dystrophy, cardiomyopathy, and/or nephropathy. [from GeneReviews]
Authors:
Jodi Y So  |  Joyce Teng   view full author information

Additional description

From OMIM
Epidermolysis bullosa simplex-2F with mottled pigmentation (EBS2F) is characterized by generalized skin blistering of intermediate severity beginning at birth, with mottled or reticulate pigmentation developing gradually. Focal keratoses of palms and soles and dystrophic, thickened nails develop over time. Although a single pathologic mutation in the KRT5 gene (P25L; 148040.0009) typically causes this phenotype, EBS patients with mottled pigmentation with other mutations in KRT5 or in other genes have been reported (summary by Has et al., 2020). For a discussion of genetic heterogeneity of the subtypes of EBS, see EBS1A (131760).  http://www.omim.org/entry/131960

Clinical features

From HPO
Punctate palmoplantar hyperkeratosis
MedGen UID:
870406
Concept ID:
C4024851
Disease or Syndrome
A palmoplantar keratosis characterized by keratoses with a "raindrop" pattern on the palmoplantar surface, skin lesions which may involve the whole of the palmoplantar surface, or may be more restricted in their distribution.
Nail dystrophy
MedGen UID:
66368
Concept ID:
C0221260
Disease or Syndrome
Onychodystrophy (nail dystrophy) refers to nail changes apart from changes of the color (nail dyschromia) and involves partial or complete disruption of the various keratinous layers of the nail plate.
Onychogryposis
MedGen UID:
82671
Concept ID:
C0263537
Disease or Syndrome
Nail that appears thick when viewed on end.
Nail dysplasia
MedGen UID:
331737
Concept ID:
C1834405
Congenital Abnormality
The presence of developmental dysplasia of the nail.
Mottled pigmentation of the trunk and proximal extremities
MedGen UID:
342031
Concept ID:
C1851551
Finding
Discrete 2 to 5-mm hyper- and hypopigmented macules
MedGen UID:
342032
Concept ID:
C1851552
Finding
Abnormal blistering of the skin
MedGen UID:
412159
Concept ID:
C2132198
Finding
The presence of one or more bullae on the skin, defined as fluid-filled blisters more than 5 mm in diameter with thin walls.
Hypoplastic fifth toenail
MedGen UID:
868713
Concept ID:
C4023116
Anatomical Abnormality
Underdeveloped nails of the fifth toes.
Intra-epidermal blistering
MedGen UID:
1779880
Concept ID:
C5539821
Finding
A type of blistering in which the lesions are located within the epidermis with loss of cell-cell adhesion of keratinocytes. In simplex EB, cleavage occurs in the basal layer, which is the innermost layer of the epidermis and consists of a single layer of basal germinative cells (mostly epidermal Keratinocytes) that proliferate and thereby produce new cells for other epidermal layers. As the cells move towards the upper layers of the epidermis they mature and eventually form cornified cells. The suprabasal cell layer lies directly above the basal layer and is composed of five to ten layers of cells.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Epidermolysis bullosa simplex with mottled pigmentation in Orphanet.

Recent clinical studies

Etiology

Turcan I, Pasmooij AM, Van den Akker PC, Lemmink H, Sinke RJ, Jonkman MF
JAMA Dermatol 2016 Oct 1;152(10):1137-1141. doi: 10.1001/jamadermatol.2016.2268. PMID: 27384765
Won KH, Lee SH, Lee MH, Rhee DY, Yeo UC, Chang SE
J Cosmet Laser Ther 2016 Nov;18(7):381-386. Epub 2016 Jul 19 doi: 10.1080/14764172.2016.1191645. PMID: 27249461
Irvine AD, McKenna KE, Jenkinson H, Hughes AE
J Invest Dermatol 1997 May;108(5):809-10. doi: 10.1111/1523-1747.ep12292263. PMID: 9129237
Uttam J, Hutton E, Coulombe PA, Anton-Lamprecht I, Yu QC, Gedde-Dahl T Jr, Fine JD, Fuchs E
Proc Natl Acad Sci U S A 1996 Aug 20;93(17):9079-84. doi: 10.1073/pnas.93.17.9079. PMID: 8799157Free PMC Article

Diagnosis

Turcan I, Pasmooij AM, Van den Akker PC, Lemmink H, Sinke RJ, Jonkman MF
JAMA Dermatol 2016 Oct 1;152(10):1137-1141. doi: 10.1001/jamadermatol.2016.2268. PMID: 27384765
Bergant Suhodolčan A, Dragoš V
Acta Dermatovenerol Alp Pannonica Adriat 2014;23(2):33-4. doi: 10.15570/actaapa.2014.8. PMID: 24964947
Echeverría-García B, Vicente A, Hernández Á, Mascaró JM, Colmenero I, Terrón A, Escámez MJ, del Río M, González-Enseñat MA, Torrelo A
Pediatr Dermatol 2013 Nov-Dec;30(6):e125-31. Epub 2012 May 29 doi: 10.1111/j.1525-1470.2012.01748.x. PMID: 22640275
Browning JC, Mohr B
Dermatol Online J 2012 Jan 15;18(1):9. PMID: 22301046
Glàsz-Bóna A, Medvecz M, Virágh Z, Hatvani Z, Blazsek A, Kárpáti S
Eur J Dermatol 2010 Nov-Dec;20(6):698-700. Epub 2010 Oct 5 doi: 10.1684/ejd.2010.1080. PMID: 20923750

Therapy

Won KH, Lee SH, Lee MH, Rhee DY, Yeo UC, Chang SE
J Cosmet Laser Ther 2016 Nov;18(7):381-386. Epub 2016 Jul 19 doi: 10.1080/14764172.2016.1191645. PMID: 27249461

Prognosis

Richardson ES, Lee JB, Hyde PH, Richard G
J Invest Dermatol 2006 Jan;126(1):79-84. doi: 10.1038/sj.jid.5700025. PMID: 16417221

Clinical prediction guides

Won KH, Lee SH, Lee MH, Rhee DY, Yeo UC, Chang SE
J Cosmet Laser Ther 2016 Nov;18(7):381-386. Epub 2016 Jul 19 doi: 10.1080/14764172.2016.1191645. PMID: 27249461
Richardson ES, Lee JB, Hyde PH, Richard G
J Invest Dermatol 2006 Jan;126(1):79-84. doi: 10.1038/sj.jid.5700025. PMID: 16417221
Irvine AD, Rugg EL, Lane EB, Hoare S, Peret C, Hughes AE, Heagerty AH
Br J Dermatol 2001 Jan;144(1):40-5. doi: 10.1046/j.1365-2133.2001.03950.x. PMID: 11167681
Uttam J, Hutton E, Coulombe PA, Anton-Lamprecht I, Yu QC, Gedde-Dahl T Jr, Fine JD, Fuchs E
Proc Natl Acad Sci U S A 1996 Aug 20;93(17):9079-84. doi: 10.1073/pnas.93.17.9079. PMID: 8799157Free PMC Article

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