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Epidermolysis bullosa simplex

MedGen UID:
86896
Concept ID:
C0079298
Disease or Syndrome
Synonyms: Epidermolysis bullosa simplex with mottled pigmentation (subtype); Epidermolysis bullosa simplex, Dowling-Meara type (subtype); Epidermolysis bullosa simplex, Weber-Cockayne type (subtype)
SNOMED CT: Epidermolysis bullosa simplex (67144006)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
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 individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
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.
 
Related genes: KRT14, KRT5
 
Monarch Initiative: MONDO:0017610
OMIM® Phenotypic series: PS131760
Orphanet: ORPHA304

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 MedlinePlus Genetics
Epidermolysis bullosa simplex is one of a group of genetic conditions called epidermolysis bullosa that cause the skin to be very fragile and to blister easily. Blisters and areas of skin loss (erosions) occur in response to minor injury or friction, such as rubbing or scratching. Epidermolysis bullosa simplex is one of the major forms of epidermolysis bullosa. The signs and symptoms of this condition vary widely among affected individuals. Blistering primarily affects the hands and feet in mild cases, and the blisters usually heal without leaving scars. Severe cases of this condition involve widespread blistering that can lead to infections, dehydration, and other medical problems. Severe cases may be life-threatening in infancy.

Researchers have identified four major types of epidermolysis bullosa simplex.

Although the types differ in severity, their features overlap significantly, and they are caused by mutations in the same genes. Most researchers now consider the major forms of this condition to be part of a single disorder with a range of signs and symptoms.

The mildest form of epidermolysis bullosa simplex, known as the localized type (formerly called the Weber-Cockayne type), is characterized by skin blistering that begins anytime between childhood and adulthood and is usually limited to the hands and feet. Later in life, skin on the palms of the hands and soles of the feet may thicken and harden (hyperkeratosis).

The Dowling-Meara type is the most severe form of epidermolysis bullosa simplex. Extensive, severe blistering can occur anywhere on the body, including the inside of the mouth, and blisters may appear in clusters. Blistering is present from birth and tends to improve with age. Affected individuals also experience abnormal nail growth and hyperkeratosis of the palms and soles.

Another form of epidermolysis bullosa simplex, known as the other generalized type (formerly called the Koebner type), is associated with widespread blisters that appear at birth or in early infancy. The blistering tends to be less severe than in the Dowling-Meara type.

Epidermolysis bullosa simplex with mottled pigmentation is characterized by patches of darker skin on the trunk, arms, and legs that fade in adulthood. This form of the disorder also involves skin blistering from early infancy, hyperkeratosis of the palms and soles, and abnormal nail growth.

Several other variants of epidermolysis bullosa simplex have been proposed, but they appear to be very rare.

In addition to the four major types described above, researchers have identified another skin condition related to epidermolysis bullosa simplex, which they call the Ogna type. It is caused by mutations in a gene that is not associated with the other types of epidermolysis bullosa simplex. It is unclear whether the Ogna type is a subtype of epidermolysis bullosa simplex or represents a separate form of epidermolysis bullosa.  https://medlineplus.gov/genetics/condition/epidermolysis-bullosa-simplex

Professional guidelines

PubMed

Sun X, Zhang J, Yang Q, Lin J
J Dermatol 2024 Apr;51(4):e131-e132. Epub 2023 Nov 10 doi: 10.1111/1346-8138.17037. PMID: 37950437
Krämer S, Lucas J, Gamboa F, Peñarrocha Diago M, Peñarrocha Oltra D, Guzmán-Letelier M, Paul S, Molina G, Sepúlveda L, Araya I, Soto R, Arriagada C, Lucky AW, Mellerio JE, Cornwall R, Alsayer F, Schilke R, Antal MA, Castrillón F, Paredes C, Serrano MC, Clark V
Spec Care Dentist 2020 Nov;40 Suppl 1(Suppl 1):3-81. doi: 10.1111/scd.12511. PMID: 33202040Free PMC Article
Mellado F, Fuentes I, Palisson F, I Vergara J, Kantor A
Cornea 2018 Apr;37(4):442-447. doi: 10.1097/ICO.0000000000001525. PMID: 29384803

Recent clinical studies

Etiology

Sussman M, Zhai L, Morquette A, Huang S, Hsu S
Clin Dermatol 2022 Sep-Oct;40(5):516-528. Epub 2022 Jan 1 doi: 10.1016/j.clindermatol.2021.12.012. PMID: 34979265
Hon KL, Chu S, Leung AKC
Curr Pediatr Rev 2022;18(3):182-190. doi: 10.2174/1573396317666210525161252. PMID: 34036913
Martina E, Diotallevi F, Radi G, Campanati A, Offidani A
Toxins (Basel) 2021 Feb 5;13(2) doi: 10.3390/toxins13020120. PMID: 33562846Free PMC Article
Mariath LM, Santin JT, Schuler-Faccini L, Kiszewski AE
An Bras Dermatol 2020 Sep-Oct;95(5):551-569. Epub 2020 Jul 8 doi: 10.1016/j.abd.2020.05.001. PMID: 32732072Free PMC Article
Irvine AD
Clin Dermatol 2005 Jan-Feb;23(1):6-14. doi: 10.1016/j.clindermatol.2004.09.014. PMID: 15708284

Diagnosis

Hon KL, Chu S, Leung AKC
Curr Pediatr Rev 2022;18(3):182-190. doi: 10.2174/1573396317666210525161252. PMID: 34036913
Mariath LM, Santin JT, Schuler-Faccini L, Kiszewski AE
An Bras Dermatol 2020 Sep-Oct;95(5):551-569. Epub 2020 Jul 8 doi: 10.1016/j.abd.2020.05.001. PMID: 32732072Free PMC Article
Uitto J, Richard G
Clin Dermatol 2005 Jan-Feb;23(1):33-40. doi: 10.1016/j.clindermatol.2004.09.015. PMID: 15708287
Irvine AD
Clin Dermatol 2005 Jan-Feb;23(1):6-14. doi: 10.1016/j.clindermatol.2004.09.014. PMID: 15708284
Haber RM, Rose TH
Arch Dermatol 1986 Aug;122(8):919-23. PMID: 3527073

Therapy

Kern JS, Sprecher E, Fernandez MF, Schauer F, Bodemer C, Cunningham T, Löwe S, Davis C, Sumeray M, Bruckner AL, Murrell DF; EASE investigators
Br J Dermatol 2023 Jan 23;188(1):12-21. doi: 10.1093/bjd/ljac001. PMID: 36689495
Martina E, Diotallevi F, Radi G, Campanati A, Offidani A
Toxins (Basel) 2021 Feb 5;13(2) doi: 10.3390/toxins13020120. PMID: 33562846Free PMC Article
Gonzalez Garcia A, Tutmaher MS, Upadhyayula SR, Sanchez Russo R, Verma S
Muscle Nerve 2019 Dec;60(6):E40-E43. Epub 2019 Oct 23 doi: 10.1002/mus.26703. PMID: 31509265
Wally V, Kitzmueller S, Lagler F, Moder A, Hitzl W, Wolkersdorfer M, Hofbauer P, Felder TK, Dornauer M, Diem A, Eiler N, Bauer JW
Orphanet J Rare Dis 2013 May 7;8:69. doi: 10.1186/1750-1172-8-69. PMID: 23651789Free PMC Article
Lewin AS, Glazer PM, Milstone LM
J Investig Dermatol Symp Proc 2005 Oct;10(1):47-61. doi: 10.1111/j.1087-0024.2005.10207.x. PMID: 16250209

Prognosis

Hon KL, Chu S, Leung AKC
Curr Pediatr Rev 2022;18(3):182-190. doi: 10.2174/1573396317666210525161252. PMID: 34036913
Kocher T, Peking P, Klausegger A, Murauer EM, Hofbauer JP, Wally V, Lettner T, Hainzl S, Ablinger M, Bauer JW, Reichelt J, Koller U
Mol Ther 2017 Nov 1;25(11):2585-2598. Epub 2017 Aug 24 doi: 10.1016/j.ymthe.2017.08.015. PMID: 28888469Free PMC Article
Uitto J, Richard G
Clin Dermatol 2005 Jan-Feb;23(1):33-40. doi: 10.1016/j.clindermatol.2004.09.015. PMID: 15708287
Irvine AD
Clin Dermatol 2005 Jan-Feb;23(1):6-14. doi: 10.1016/j.clindermatol.2004.09.014. PMID: 15708284
Fine JD, Johnson LB, Wright JT
Pediatrician 1991;18(3):175-87. PMID: 1946084

Clinical prediction guides

Hon KL, Chu S, Leung AKC
Curr Pediatr Rev 2022;18(3):182-190. doi: 10.2174/1573396317666210525161252. PMID: 34036913
Kocher T, Peking P, Klausegger A, Murauer EM, Hofbauer JP, Wally V, Lettner T, Hainzl S, Ablinger M, Bauer JW, Reichelt J, Koller U
Mol Ther 2017 Nov 1;25(11):2585-2598. Epub 2017 Aug 24 doi: 10.1016/j.ymthe.2017.08.015. PMID: 28888469Free PMC Article
Risteli M, Ruotsalainen H, Salo AM, Sormunen R, Sipilä L, Baker NL, Lamandé SR, Vimpari-Kauppinen L, Myllylä R
J Biol Chem 2009 Oct 9;284(41):28204-28211. Epub 2009 Aug 20 doi: 10.1074/jbc.M109.038190. PMID: 19696018Free PMC Article
McLean WH, Smith FJ, Cassidy AJ
J Investig Dermatol Symp Proc 2005 Oct;10(1):31-6. doi: 10.1111/j.1087-0024.2005.10205.x. PMID: 16250207
Schröder R, Mundegar RR, Treusch M, Schlegel U, Blümcke I, Owaribe K, Magin TM
Eur J Cell Biol 1997 Oct;74(2):165-71. PMID: 9352221

Recent systematic reviews

Martina E, Diotallevi F, Radi G, Campanati A, Offidani A
Toxins (Basel) 2021 Feb 5;13(2) doi: 10.3390/toxins13020120. PMID: 33562846Free PMC Article
Krämer S, Lucas J, Gamboa F, Peñarrocha Diago M, Peñarrocha Oltra D, Guzmán-Letelier M, Paul S, Molina G, Sepúlveda L, Araya I, Soto R, Arriagada C, Lucky AW, Mellerio JE, Cornwall R, Alsayer F, Schilke R, Antal MA, Castrillón F, Paredes C, Serrano MC, Clark V
Spec Care Dentist 2020 Nov;40 Suppl 1(Suppl 1):3-81. doi: 10.1111/scd.12511. PMID: 33202040Free PMC Article
Xie D, Bilgic-Temel A, Abu Alrub N, Murrell DF
Pediatr Dermatol 2019 Jul;36(4):430-436. Epub 2019 Jun 9 doi: 10.1111/pde.13866. PMID: 31177584

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