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Junctional epidermolysis bullosa gravis of Herlitz

MedGen UID:
36328
Concept ID:
C0079683
Disease or Syndrome
Synonyms: EPIDERMOLYSIS BULLOSA JUNCTIONALIS, HERLITZ TYPE; Epidermolysis Bullosa Letalis; Epidermolysis bullosa, junctional, Herlitz-Pearson type; EPIDERMOLYSIS BULLOSA, JUNCTIONAL, NON-HERLITZ TYPE; Herlitz-Pearson type epidermolysis bullosa; Herlitz-type junctional epidermolysis bullosa; JEB-HERLITZ TYPE; Junctional Epidermolysis Bullosa; LAMA3-Related Junctional Epidermolysis Bullosa; LAMB3-Related Junctional Epidermolysis Bullosa; LAMC2-Related Junctional Epidermolysis Bullosa
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, 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 recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Epidermolysis bullosa, junctional Herlitz-Pearson type (79855003); Epidermolysis bullosa hereditaria letalis (79855003); Junctional epidermolysis bullosa gravis of Herlitz (400140006); Epidermolysis bullosa letalis (400140006); Junctional epidermolysis bullosa, lethal type, Herlitz (400140006); Herlitz syndrome (400140006); Herlitz's disease (400140006)
 
Genes (locations): LAMA3 (18q11.2); LAMB3 (1q32.2); LAMC2 (1q25.3)
OMIM®: 226700
Orphanet: ORPHA79404

Disease characteristics

Excerpted from the GeneReview: Junctional Epidermolysis Bullosa
Junctional epidermolysis bullosa (JEB) is characterized by fragility of the skin and mucous membranes, manifest by blistering with little or no trauma. Blistering may be severe and granulation tissue can form on the skin around the oral and nasal cavities, fingers and toes, and internally around the upper airway. Blisters generally heal with no significant scarring. Broad classification of JEB includes JEB generalized severe and JEB generalized intermediate. In JEB generalized severe, blisters are present at birth or become apparent in the neonatal period. Congenital malformations of the urinary tract and bladder may also occur. In JEB generalized intermediate, the phenotype may be mild with blistering localized to hands, feet, knees, and elbows with or without renal or ureteral involvement. Some individuals never blister after the newborn period. Additional features shared by JEB and the other major forms of epidermolysis bullosa (EB) include congenital localized absence of skin (aplasia cutis congenita), milia, nail dystrophy, scarring alopecia, hypotrichosis, pseudosyndactyly, and other contractures. [from GeneReviews]
Authors:
Ellen G Pfendner  |  Anne W Lucky   view full author information

Additional descriptions

From OMIM
Junctional epidermolysis bullosa is an autosomal recessive skin disorder in which blisters occur at the level of the lamina lucida in the skin basement membrane. Fine et al. (2000, 2008) proposed classification of the different types of JEB into 'Herlitz' and 'non-Herlitz' types based on severity; the Herlitz type is more severe and often results in early death. Fine et al. (2000, 2008) also eliminated the term 'hemidesmosomal,' which had previously been proposed for some forms of JEB (Uitto et al., 1997). Pulkkinen and Uitto (1999) reviewed the pathophysiology and phenotypic and genetic heterogeneity of the various forms of epidermolysis bullosa.  http://www.omim.org/entry/226700
From GHR
Junctional epidermolysis bullosa (JEB) is a major form of epidermolysis bullosa, a group of genetic conditions that cause the skin to be very fragile and to blister easily. Blisters and areas of skin loss (erosions) form in response to minor injury or friction, such as rubbing or scratching. Researchers classify junctional epidermolysis bullosa into two main types: JEB generalized severe (formerly known as Herlitz JEB) and JEB generalized intermediate (formerly known as non-Herlitz JEB). Although the types differ in severity, their features overlap significantly, and they can be caused by mutations in the same genes.JEB generalized severe is the more serious form of the condition. From birth or early infancy, affected individuals have blistering over large regions of the body. Blistering also affects the mucous membranes, such as the moist lining of the mouth and digestive tract, which can make it difficult to eat and digest food. As a result, many affected children are undernourished and grow slowly. The extensive blistering leads to scarring and the formation of red, bumpy patches called granulation tissue. Granulation tissue bleeds easily and profusely, making affected infants susceptible to serious infections and loss of necessary proteins, minerals, and fluids. Additionally, a buildup of granulation tissue in the airway can lead to a weak, hoarse cry and difficulty breathing.Other complications of JEB generalized severe can include fusion of the fingers and toes, abnormalities of the fingernails and toenails, joint deformities (contractures) that limit movement, hair loss (alopecia), and thinning of the protective outer layer (enamel) of the teeth. Because the signs and symptoms of JEB generalized severe are so serious, infants with this condition usually do not survive beyond the first year of life.The milder form of junctional epidermolysis bullosa is called JEB generalized intermediate. The blistering associated with JEB generalized intermediate may be limited to the hands, feet, knees, and elbows, and it often improves after the newborn period. Other characteristic features of this form of the condition include hair loss, abnormal fingernails and toenails, and irregular tooth enamel. Most affected individuals do not have extensive scarring or granulation tissue formation, so breathing difficulties and other severe complications are rare. JEB generalized intermediate is typically associated with a normal lifespan.  https://ghr.nlm.nih.gov/condition/junctional-epidermolysis-bullosa

Clinical features

From HPO
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Pyloric stenosis
MedGen UID:
18780
Concept ID:
C0034194
Pathologic Function
Narrowing of the pyloric canal with varied etiology. A common form is due to muscle hypertrophy (PYLORIC STENOSIS, HYPERTROPHIC) seen in infants.
Syndactyly
MedGen UID:
52619
Concept ID:
C0039075
Congenital Abnormality
A congenital anomaly of the hand or foot, marked by the webbing between adjacent fingers or toes. Syndactylies are classified as complete or incomplete by the degree of joining. Syndactylies can also be simple or complex. Simple syndactyly indicates joining of only skin or soft tissue; complex syndactyly marks joining of bony elements.
Hypoplasia of dental enamel
MedGen UID:
3730
Concept ID:
C0011351
Disease or Syndrome
A form of amelogenesis imperfecta characterized by incomplete formation of the dental enamel and transmitted as an X-linked or autosomal dominant trait.
Syndactyly
MedGen UID:
52619
Concept ID:
C0039075
Congenital Abnormality
A congenital anomaly of the hand or foot, marked by the webbing between adjacent fingers or toes. Syndactylies are classified as complete or incomplete by the degree of joining. Syndactylies can also be simple or complex. Simple syndactyly indicates joining of only skin or soft tissue; complex syndactyly marks joining of bony elements.
Carious teeth
MedGen UID:
8288
Concept ID:
C0011334
Disease or Syndrome
Caries is a multifactorial bacterial infection affecting the structure of the tooth. This term has been used to describe the presence of more than expected dental caries.
Hypoplasia of dental enamel
MedGen UID:
3730
Concept ID:
C0011351
Disease or Syndrome
A form of amelogenesis imperfecta characterized by incomplete formation of the dental enamel and transmitted as an X-linked or autosomal dominant trait.
Hypoplasia of dental enamel
MedGen UID:
3730
Concept ID:
C0011351
Disease or Syndrome
A form of amelogenesis imperfecta characterized by incomplete formation of the dental enamel and transmitted as an X-linked or autosomal dominant trait.
Atrophic scars
MedGen UID:
57875
Concept ID:
C0162154
Pathologic Function
Atrophic scars
MedGen UID:
57875
Concept ID:
C0162154
Pathologic Function
Nail dystrophy
MedGen UID:
66368
Concept ID:
C0221260
Disease or Syndrome
Deformity or discoloration of a fingernail or toenail.
Milia
MedGen UID:
87528
Concept ID:
C0345996
Anatomical Abnormality
Presence of multiple small cysts containing keratin (skin protein) and presenting as tiny pearly-white bumps just under the surface of the skin.
Nail dysplasia
MedGen UID:
331737
Concept ID:
C1834405
Congenital Abnormality
The presence of developmental dysplasia of the nail.
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.
Congenital localized absence of skin
MedGen UID:
388677
Concept ID:
C2673597
Finding
Junctional split
MedGen UID:
867365
Concept ID:
C4021730
Disease or Syndrome
The formation of bullae (blisters) with cleavage in the lamina lucida layer of the skin.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Junctional epidermolysis bullosa gravis of Herlitz in Orphanet.

Recent clinical studies

Etiology

Wang H, Yang Y, Zhou J, Cao J, He X, Li L, Gao S, Mao B, Tian P, Zhou A
Medicine (Baltimore) 2018 Dec;97(49):e13225. doi: 10.1097/MD.0000000000013225. PMID: 30544381Free PMC Article
Vahidnezhad H, Youssefian L, Saeidian AH, Touati A, Sotoudeh S, Jazayeri A, Guy A, Lovell PA, Liu L, Kariminejad A, McGrath JA, Zeinali S, Uitto J
Hum Mutat 2018 Oct;39(10):1349-1354. Epub 2018 Aug 3 doi: 10.1002/humu.23592. PMID: 30016581
Yenamandra VK, Vellarikkal SK, Kumar M, Chowdhury MR, Jayarajan R, Verma A, Scaria V, Sivasubbu S, Ray SB, Dinda AK, Kabra M, Kaur P, Sharma VK, Sethuraman G
J Dermatol Sci 2017 Apr;86(1):30-36. Epub 2016 Dec 29 doi: 10.1016/j.jdermsci.2016.12.020. PMID: 28087116
Hammersen J, Has C, Naumann-Bartsch N, Stachel D, Kiritsi D, Söder S, Tardieu M, Metzler M, Bruckner-Tuderman L, Schneider H
J Invest Dermatol 2016 Nov;136(11):2150-2157. Epub 2016 Jun 29 doi: 10.1016/j.jid.2016.06.609. PMID: 27375110
Kelly-Mancuso G, Kopelan B, Azizkhan RG, Lucky AW
Pediatr Dermatol 2014 Mar-Apr;31(2):159-62. Epub 2013 May 31 doi: 10.1111/pde.12157. PMID: 23721227

Diagnosis

Hoffmann J, Casetti F, Reimer A, Leppert J, Grüninger G, Has C
Acta Derm Venereol 2019 Apr 1;99(4):460-461. doi: 10.2340/00015555-3133. PMID: 30673110
Vahidnezhad H, Youssefian L, Saeidian AH, Touati A, Sotoudeh S, Jazayeri A, Guy A, Lovell PA, Liu L, Kariminejad A, McGrath JA, Zeinali S, Uitto J
Hum Mutat 2018 Oct;39(10):1349-1354. Epub 2018 Aug 3 doi: 10.1002/humu.23592. PMID: 30016581
Ko L, Griggs CL, Mylonas KS, Masiakos PT, Kroshinsky D
J Pediatr 2018 Feb;193:261-264.e1. Epub 2017 Dec 1 doi: 10.1016/j.jpeds.2017.09.023. PMID: 29198538
Hammersen J, Has C, Naumann-Bartsch N, Stachel D, Kiritsi D, Söder S, Tardieu M, Metzler M, Bruckner-Tuderman L, Schneider H
J Invest Dermatol 2016 Nov;136(11):2150-2157. Epub 2016 Jun 29 doi: 10.1016/j.jid.2016.06.609. PMID: 27375110
Hauschild R, Wollina U, Bruckner-Tuderman L
J Eur Acad Dermatol Venereol 2001 Jan;15(1):73-6. PMID: 11451332

Therapy

Reimer A, Laszig R, Pfeiffer J, Eberwein P, Mittelviefhaus H, Bruckner-Tuderman L, Has C
Acta Derm Venereol 2018 Jul 11;98(7):711-712. doi: 10.2340/00015555-2934. PMID: 29963681
Chiaverini C, Passeron T, Lacour JP
J Am Acad Dermatol 2016 Dec;75(6):e223-e224. doi: 10.1016/j.jaad.2016.08.005. PMID: 27846969
De Rosa L, Carulli S, Cocchiarella F, Quaglino D, Enzo E, Franchini E, Giannetti A, De Santis G, Recchia A, Pellegrini G, De Luca M
Stem Cell Reports 2014 Jan 14;2(1):1-8. Epub 2013 Dec 26 doi: 10.1016/j.stemcr.2013.11.001. PMID: 24511464Free PMC Article
Melo SP, Lisowski L, Bashkirova E, Zhen HH, Chu K, Keene DR, Marinkovich MP, Kay MA, Oro AE
Mol Ther 2014 Apr;22(4):725-33. Epub 2014 Jan 6 doi: 10.1038/mt.2013.290. PMID: 24390279Free PMC Article
Pérez A, Almaani N, Stefanato CM, BhogaL B, Groves RW, Mellerio JE, McGrath JA
Clin Exp Dermatol 2010 Dec;35(8):881-4. doi: 10.1111/j.1365-2230.2010.03828.x. PMID: 20456391

Prognosis

Wang H, Yang Y, Zhou J, Cao J, He X, Li L, Gao S, Mao B, Tian P, Zhou A
Medicine (Baltimore) 2018 Dec;97(49):e13225. doi: 10.1097/MD.0000000000013225. PMID: 30544381Free PMC Article
Vahidnezhad H, Youssefian L, Saeidian AH, Touati A, Sotoudeh S, Jazayeri A, Guy A, Lovell PA, Liu L, Kariminejad A, McGrath JA, Zeinali S, Uitto J
Hum Mutat 2018 Oct;39(10):1349-1354. Epub 2018 Aug 3 doi: 10.1002/humu.23592. PMID: 30016581
Hammersen J, Has C, Naumann-Bartsch N, Stachel D, Kiritsi D, Söder S, Tardieu M, Metzler M, Bruckner-Tuderman L, Schneider H
J Invest Dermatol 2016 Nov;136(11):2150-2157. Epub 2016 Jun 29 doi: 10.1016/j.jid.2016.06.609. PMID: 27375110
Yang CS, Kroshinksy D, Cummings BM
Am J Clin Dermatol 2014 Oct;15(5):445-50. doi: 10.1007/s40257-014-0091-7. PMID: 25117154
Kelly-Mancuso G, Kopelan B, Azizkhan RG, Lucky AW
Pediatr Dermatol 2014 Mar-Apr;31(2):159-62. Epub 2013 May 31 doi: 10.1111/pde.12157. PMID: 23721227

Clinical prediction guides

Vahidnezhad H, Youssefian L, Saeidian AH, Touati A, Sotoudeh S, Jazayeri A, Guy A, Lovell PA, Liu L, Kariminejad A, McGrath JA, Zeinali S, Uitto J
Hum Mutat 2018 Oct;39(10):1349-1354. Epub 2018 Aug 3 doi: 10.1002/humu.23592. PMID: 30016581
Melo SP, Lisowski L, Bashkirova E, Zhen HH, Chu K, Keene DR, Marinkovich MP, Kay MA, Oro AE
Mol Ther 2014 Apr;22(4):725-33. Epub 2014 Jan 6 doi: 10.1038/mt.2013.290. PMID: 24390279Free PMC Article
Kittridge A, Patel R, Novoa R, Tamburro J
Pediatr Dermatol 2014 Jul-Aug;31(4):530-2. Epub 2012 Dec 26 doi: 10.1111/pde.12018. PMID: 23278291
Yuen WY, Duipmans JC, Molenbuur B, Herpertz I, Mandema JM, Jonkman MF
Br J Dermatol 2012 Aug;167(2):374-82. Epub 2012 Jul 5 doi: 10.1111/j.1365-2133.2012.10997.x. PMID: 22512697
Kho YC, Rhodes LM, Robertson SJ, Su J, Varigos G, Robertson I, Hogan P, Orchard D, Murrell DF
Arch Dermatol 2010 Jun;146(6):635-40. doi: 10.1001/archdermatol.2010.109. PMID: 20566927

Recent systematic reviews

Montaudié H, Chiaverini C, Sbidian E, Charlesworth A, Lacour JP
Orphanet J Rare Dis 2016 Aug 20;11(1):117. doi: 10.1186/s13023-016-0489-9. PMID: 27544590Free PMC Article

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