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Adult junctional epidermolysis bullosa(GABEB)

MedGen UID:
82798
Concept ID:
C0268374
Disease or Syndrome
Synonyms: COL17A1-Related Junctional Epidermolysis Bullosa; Epidermolysis bullosa junctionalis, disentis type; EPIDERMOLYSIS BULLOSA JUNCTIONALIS, NON-HERLITZ TYPE; Epidermolysis bullosa junctionalis, progressive; Epidermolysis bullosa junctionalis, severe nonlethal; Epidermolysis bullosa, generalized atrophic benign; EPIDERMOLYSIS BULLOSA, JUNCTIONAL, NON-HERLITZ TYPE; Epidermolysis bullosa, junctional, non-herlitz type, somatic mosaic revertant; GABEB; LAMA3-Related Junctional Epidermolysis Bullosa; LAMB3-Related Junctional Epidermolysis Bullosa; LAMC2-Related Junctional Epidermolysis Bullosa
Modes of inheritance:
Heterogeneous
MedGen UID:
67020
Concept ID:
C0242960
Organism Attribute
Source: HPO
The presence of apparently similar characters for which the genetic evidence indicates that different genes or different genetic mechanisms are involved in different pedigrees. In clinical settings genetic heterogeneity refers to the presence of a variety of genetic defects which cause the same disease, often due to mutations at different loci on the same gene, a finding common to many human diseases including ALZHEIMER DISEASE; CYSTIC FIBROSIS; LIPOPROTEIN LIPASE DEFICIENCY, FAMILIAL; and POLYCYSTIC KIDNEY DISEASES. (Rieger, et al., Glossary of Genetics: Classical and Molecular, 5th ed; Segen, Dictionary of Modern Medicine, 1992)
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: Junctional epidermolysis bullosa non-Herlitz type (724225008)
 
Genes (locations): COL17A1 (10q25.1); ITGB4 (17q25.1); LAMA3 (18q11.2); LAMB3 (1q32.2); LAMC2 (1q25.3)
OMIM®: 226650
Orphanet: ORPHA89840

Definition

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]

Additional description

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
Camptodactyly of finger
MedGen UID:
98041
Concept ID:
C0409348
Finding
The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers cannot be extended to 180 degrees by either active or passive extension.
Palmar hyperhidrosis
MedGen UID:
346478
Concept ID:
C1856953
Finding
Plantar hyperkeratosis
MedGen UID:
341658
Concept ID:
C1856954
Finding
Hyperkeratosis affecting the sole of the foot.
Camptodactyly of finger
MedGen UID:
98041
Concept ID:
C0409348
Finding
The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers cannot be extended to 180 degrees by either active or passive extension.
Camptodactyly of finger
MedGen UID:
98041
Concept ID:
C0409348
Finding
The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers cannot be extended to 180 degrees by either active or passive extension.
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.
Partial congenital absence of teeth
MedGen UID:
43794
Concept ID:
C0020608
Congenital Abnormality
Tooth agenesis in some form is a common human anomaly that affects approximately 20% of the population. Although tooth agenesis is associated with numerous syndromes, several case reports describe nonsyndromic forms that are either sporadic or familial in nature, as reviewed by Gorlin et al. (1990). The incidence of familial tooth agenesis varies with each class of teeth. Most commonly affected are third molars (wisdom teeth), followed by either upper lateral incisors or lower second premolars; agenesis involving first and second molars is very rare. Also see 114600 and 302400. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). Faulty use of the terms, however, have confounded their use. The term 'partial anodontia' is obsolete (Salinas, 1978). Genetic Heterogeneity of Selective Tooth Agenesis Other forms of selective tooth agenesis include STHAG2 (602639), mapped to chromosome 16q12; STHAG3 (604625), caused by mutation in the PAX9 gene (167416) on chromosome 14q12; STHAG4 (150400), caused by mutation in the WNT10A gene (606268) on chromosome 2q35; STHAG5 (610926), mapped to chromosome 10q11; STHAG7 (616724), caused by mutation in the LRP6 gene (603507) on chromosome 12p13; STHAG8 (617073), caused by mutation in the WNT10B gene (601906) on chromosome 12q13; STHAG9 (617275), caused by mutation in the GREM2 gene (608832) on chromosome 1q43; and STHAGX1 (313500), caused by mutation in the EDA gene (300451) on chromosome Xq13. A type of selective tooth agenesis that was formerly designated STHAG6 has been incorporated into the dental anomalies and short stature syndrome (DASS; 601216). Of 34 unrelated patients with nonsyndromic tooth agenesis, van den Boogaard et al. (2012) found that 56% (19 patients) had mutations in the WNT10A gene (STHAG4), whereas only 3% and 9% had mutations in the MSX1 (STHAG1) and PAX9 (STHAG3) genes, respectively. The authors concluded that WNT10A is a major gene in the etiology of isolated hypodontia. Genotype-Phenotype Correlations Yu et al. (2016) observed that the most frequently missing permanent teeth in WNT10B-associated oligodontia were the lateral incisors (83.3%), whereas premolars were missing only 51.4% of the time, which they noted was a pattern 'clearly different' from the oligodontia patterns resulting from WNT10A mutations. They also stated that the selective pattern in WNT10B mutants was different from that associated with mutations in other genes, such as MSX1, in which second premolars are missing, and PAX9, in which there is agenesis of molars.
Oral mucosal blisters
MedGen UID:
208888
Concept ID:
C0853945
Sign or Symptom
Blisters arising in the mouth.
Camptodactyly of finger
MedGen UID:
98041
Concept ID:
C0409348
Finding
The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers cannot be extended to 180 degrees by either active or passive extension.
Nail dystrophy
MedGen UID:
66368
Concept ID:
C0221260
Disease or Syndrome
Deformity or discoloration of a fingernail or toenail.
Oral mucosal blisters
MedGen UID:
208888
Concept ID:
C0853945
Sign or Symptom
Blisters arising in the mouth.
Nail dysplasia
MedGen UID:
331737
Concept ID:
C1834405
Congenital Abnormality
The presence of developmental dysplasia of the nail.
Palmar hyperhidrosis
MedGen UID:
346478
Concept ID:
C1856953
Finding
Plantar hyperkeratosis
MedGen UID:
341658
Concept ID:
C1856954
Finding
Hyperkeratosis affecting the sole of the foot.
Fragile nails
MedGen UID:
341661
Concept ID:
C1856963
Finding
Nails that easily break.

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
Hon KL, Li JJ, Cheng BL, Luk DC, Murrell DF, Choi PC, Leung AK
J Dermatolog Treat 2015 Apr;26(2):178-82. Epub 2014 May 15 doi: 10.3109/09546634.2014.915002. PMID: 24724596
Yuen WY, Huizinga J, Jonkman MF
J Am Acad Dermatol 2013 Jan;68(1):93-7, 97.e1-2. Epub 2012 May 26 doi: 10.1016/j.jaad.2012.04.012. PMID: 22633040
Yuen WY, Jonkman MF
J Am Acad Dermatol 2011 Oct;65(4):780-789. Epub 2011 May 31 doi: 10.1016/j.jaad.2010.07.006. PMID: 21624701
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

Diagnosis

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
Lucky AW, Dagaonkar N, Lammers K, Husami A, Kissell D, Zhang K
Pediatr Dermatol 2018 Mar;35(2):188-197. Epub 2018 Jan 15 doi: 10.1111/pde.13392. PMID: 29334134
Kiritsi D, Huilaja L, Franzke CW, Kokkonen N, Pazzagli C, Schwieger-Briel A, Larmas M, Bruckner-Tuderman L, Has C, Tasanen K
Acta Derm Venereol 2015 Sep;95(7):849-51. doi: 10.2340/00015555-2073. PMID: 25708563
Lee M, Chen Q, Wang H, Zhang J, Lin Z, Yang Y
Acta Derm Venereol 2015 Jan;95(1):112-3. doi: 10.2340/00015555-1888. PMID: 24807042
Hon KL, Li JJ, Cheng BL, Luk DC, Murrell DF, Choi PC, Leung AK
J Dermatolog Treat 2015 Apr;26(2):178-82. Epub 2014 May 15 doi: 10.3109/09546634.2014.915002. PMID: 24724596

Therapy

Kaipe H, Carlson LM, Erkers T, Nava S, Molldén P, Gustafsson B, Qian H, Li X, Hashimoto T, Sadeghi B, Alheim M, Ringdén O
Stem Cells Dev 2015 Jun 15;24(12):1471-82. Epub 2015 Mar 13 doi: 10.1089/scd.2014.0568. PMID: 25658253Free 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
Fine JD, Johnson LB, Weiner M, Suchindran C
J Pediatr 2008 Feb;152(2):276-80. Epub 2007 Oct 22 doi: 10.1016/j.jpeds.2007.06.039. PMID: 18206702
Mabuchi E, Umegaki N, Murota H, Nakamura T, Tamai K, Katayama I
Br J Dermatol 2007 Sep;157(3):596-8. Epub 2007 Jun 26 doi: 10.1111/j.1365-2133.2007.08046.x. PMID: 17596158
Mavilio F, Pellegrini G, Ferrari S, Di Nunzio F, Di Iorio E, Recchia A, Maruggi G, Ferrari G, Provasi E, Bonini C, Capurro S, Conti A, Magnoni C, Giannetti A, De Luca M
Nat Med 2006 Dec;12(12):1397-402. Epub 2006 Nov 19 doi: 10.1038/nm1504. PMID: 17115047

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
Hon KL, Li JJ, Cheng BL, Luk DC, Murrell DF, Choi PC, Leung AK
J Dermatolog Treat 2015 Apr;26(2):178-82. Epub 2014 May 15 doi: 10.3109/09546634.2014.915002. PMID: 24724596
Yuen WY, Jonkman MF
J Am Acad Dermatol 2011 Oct;65(4):780-789. Epub 2011 May 31 doi: 10.1016/j.jaad.2010.07.006. PMID: 21624701
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
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

Clinical prediction guides

Schwieger-Briel A, Chakkittakandiyil A, Lara-Corrales I, Aujla N, Lane AT, Lucky AW, Bruckner AL, Pope E
Pediatr Dermatol 2015 Jan-Feb;32(1):41-52. Epub 2014 Mar 20 doi: 10.1111/pde.12317. PMID: 24650374
Loh CC, Kim J, Su JC, Daniel BS, Venugopal SS, Rhodes LM, Intong LR, Law MG, Murrell DF
J Am Acad Dermatol 2014 Jan;70(1):89-97.e1-13. doi: 10.1016/j.jaad.2013.09.041. PMID: 24355263
Pasmooij AM, Nijenhuis M, Brander R, Jonkman MF
J Invest Dermatol 2012 May;132(5):1374-83. Epub 2012 Feb 9 doi: 10.1038/jid.2011.477. PMID: 22318390
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
Fassihi H, Ashton GH, Denyer J, Mellerio JE, Mason G, McGrath JA
Clin Exp Dermatol 2005 Mar;30(2):180-2. doi: 10.1111/j.1365-2230.2004.01704.x. PMID: 15725250

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