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Junctional epidermolysis bullosa with pyloric atresia(JEB5B)

MedGen UID:
1810975
Concept ID:
C5676875
Disease or Syndrome
Synonyms: Aplasia cutis congenita with gastrointestinal atresia; Carmi syndrome; EB-PA-ACC; Epidermolysis bullosa junctionalis with pyloric atresia; Epidermolysis bullosa with pyloric atresia; EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA; Epidermolysis bullosa, junctional, with pyloric atresia and aplasia cutis congenita; ITGA6-Related Epidermolysis Bullosa with Pyloric Atresia; ITGB4-Related Epidermolysis Bullosa with Pyloric Atresia
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).
 
Genes (locations): ITGB4 (17q25.1); PLEC (8q24.3)
 
Monarch Initiative: MONDO:0009183
OMIM®: 226730
Orphanet: ORPHA79403

Definition

Epidermolysis bullosa with pyloric atresia (EB-PA) is characterized by fragility of the skin and mucous membranes, manifested by blistering with little or no trauma; congenital pyloric atresia; and ureteral and renal anomalies (dysplastic/multicystic kidney, hydronephrosis/hydroureter, ureterocele, duplicated renal collecting system, absent bladder). The course of EB-PA is usually severe and often lethal in the neonatal period. Most affected children succumb as neonates; those who survive may have severe blistering with formation of granulation tissue on the skin around the mouth, nose, fingers, and toes, and internally around the trachea. However, some affected individuals have little or no blistering later in life. Additional features shared by EB-PA and the other major forms of EB include congenital localized absence of skin (aplasia cutis congenita) affecting the extremities and/or head, milia, nail dystrophy, scarring alopecia, hypotrichosis, contractures, and dilated cardiomyopathy. [from GeneReviews]

Additional descriptions

From OMIM
Junctional epidermolysis bullosa 5B with pyloric atresia (JEB5B) is an autosomal recessive blistering disease of skin and mucous membranes. Severity of skin involvement ranges from extensive full thickness skin loss (aplasia cutis congenita) to mild epidermolysis bullosa that improves with age. The plane of skin cleavage is through the lamina lucida of the cutaneous basement membrane zone. Pyloric atresia is usually evident within a few days to weeks of life. Atresia may occur at other gastrointestinal sites including the esophagus and duodenum. JEB5B is usually lethal within the first few weeks of life despite surgical correction of pyloric atresia. Milder, non-lethal forms with less skin blistering have been reported (summary by Has et al., 2020). Another form of junctional epidermolysis bullosa with pyloric atresia (JEB6; 619817) is caused by mutations in the integrin-alpha-6 gene (ITGA6; 147556). See also epidermolysis bullosa simplex with pyloric atresia (EBS5C; 612138), which is caused by mutations in the PLEC1 gene (601282). For a discussion of genetic heterogeneity of the subtypes of JEB, see JEB1A (226650). Reviews Has et al. (2020) reviewed the clinical and genetic aspects, genotype-phenotype correlations, disease-modifying factors, and natural history of epidermolysis bullosa. In a study involving 265 cases of junctional or hemidesmosomal EB, Varki et al. (2006) reviewed the clinical and molecular heterogeneity of these subtypes of EB, discussed exceptions to the general rules on genotype-phenotype correlations, and noted unusual phenotypes and genetics observed in patients and families with EB.  http://www.omim.org/entry/226730
From MedlinePlus Genetics
Because the signs and symptoms of EB-PA are so severe, many infants with this condition do not survive beyond the first year of life. In those who survive, the condition may improve with time; some affected individuals have little or no blistering later in life. However, many affected individuals who live past infancy experience severe health problems, including blistering and the formation of red, bumpy patches called granulation tissue. Granulation tissue most often forms on the skin around the mouth, nose, fingers, and toes. It can also build up in the airway, leading to difficulty breathing.

Other complications of EB-PA can include fusion of the skin between the fingers and toes, abnormalities of the fingernails and toenails, joint deformities (contractures) that restrict movement, and hair loss (alopecia). Some affected individuals are also born with malformations of the urinary tract, including the kidneys and bladder.

People with EB-PA are also born with pyloric atresia, which is a blockage (obstruction) of the lower part of the stomach (the pylorus). This obstruction prevents food from emptying out of the stomach into the intestine. Signs of pyloric atresia include vomiting, a swollen (distended) abdomen, and an absence of stool. Pyloric atresia is life-threatening and must be repaired with surgery soon after birth.

Epidermolysis bullosa with pyloric atresia (EB-PA) is a condition that affects the skin and digestive tract. This condition is one of several forms of epidermolysis bullosa, a group of genetic conditions that cause the skin to be fragile and to blister easily. Affected infants are often born with widespread blistering and areas of missing skin. Blisters continue to appear in response to minor injury or friction, such as rubbing or scratching. Most often, blisters occur over the whole body and affect mucous membranes such as the moist lining of the mouth and digestive tract.  https://medlineplus.gov/genetics/condition/epidermolysis-bullosa-with-pyloric-atresia

Clinical features

From HPO
Urethrovesical occlusion
MedGen UID:
392960
Concept ID:
C2673586
Pathologic Function
Blockage of the flow of urine from the bladder into the urethra.
Esophageal atresia
MedGen UID:
4545
Concept ID:
C0014850
Congenital Abnormality
A developmental defect resulting in complete obliteration of the lumen of the esophagus such that the esophagus ends in a blind pouch rather than connecting to the stomach.
Intractable diarrhea
MedGen UID:
148164
Concept ID:
C0743178
Disease or Syndrome
Congenital pyloric atresia
MedGen UID:
870867
Concept ID:
C4025327
Congenital Abnormality
Congenital atresia of the pylorus.
Arthrogryposis multiplex congenita
MedGen UID:
1830310
Concept ID:
C5779613
Disease or Syndrome
Multiple congenital contractures in different body areas.
Elevated maternal serum alpha-fetoprotein
MedGen UID:
152853
Concept ID:
C0740927
Finding
An elevation of alpha-feto protein in the maternal serum.
Enamel hypoplasia
MedGen UID:
3730
Concept ID:
C0011351
Disease or Syndrome
Developmental hypoplasia of the dental enamel.
Ectropion
MedGen UID:
4448
Concept ID:
C0013592
Disease or Syndrome
An outward turning (eversion) or rotation of the eyelid margin.
Atrophic scars
MedGen UID:
57875
Concept ID:
C0162154
Pathologic Function
Scars that form a depression compared to the level of the surrounding skin because of damage to the collagen, fat or other tissues below the skin.
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.
Fragile skin
MedGen UID:
66826
Concept ID:
C0241181
Finding
Skin that splits easily with minimal injury.
Anonychia
MedGen UID:
120563
Concept ID:
C0265998
Congenital Abnormality
Congenital anonychia is defined as the absence of fingernails and toenails. Anonychia and its milder phenotypic variant, hyponychia, usually occur as a feature of genetic syndromes, in association with significant skeletal and limb anomalies. Isolated nonsyndromic congenital anonychia/hyponychia is a rare entity that usually follows autosomal recessive inheritance with variable expression, even within a given family. The nail phenotypes observed range from no nail field to a nail field of reduced size with an absent or rudimentary nail (summary by Bruchle et al., 2008). This form of nail disorder is referred to here as nonsyndromic congenital nail disorder-4 (NDNC4). For a list of other nonsyndromic congenital nail disorders and a discussion of genetic heterogeneity, see NDNC1 (161050).
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.
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.
Axillary pterygium
MedGen UID:
335019
Concept ID:
C1844738
Finding
Presence of a cutaneous membrane (flap) in the armpit.
Aplasia cutis congenita on trunk or limbs
MedGen UID:
400308
Concept ID:
C1863496
Finding
A developmental defect resulting in the congenital absence of skin on the trunk or the limbs.
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.
Lamina lucida cleavage
MedGen UID:
867365
Concept ID:
C4021730
Finding
The formation of bullae (blisters) with cleavage in the lamina lucida layer of the skin.
Hypoplastic dermoepidermal hemidesmosomes
MedGen UID:
1697259
Concept ID:
C5209220
Finding
Underdeveloped hemidesmosomes at the dermoepidermal junction. Hemidesmosomes are the specialized junctional complexes, that contribute to the attachment of epithelial cells to the underlying basement membrane in stratified and other complex epithelia, such as the skin.
Polyhydramnios
MedGen UID:
6936
Concept ID:
C0020224
Pathologic Function
The presence of excess amniotic fluid in the uterus during pregnancy.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVJunctional epidermolysis bullosa with pyloric atresia

Professional guidelines

PubMed

Nakamura H, Natsuga K, Nishie W, McMillan JR, Nakamura H, Sawamura D, Akiyama M, Shimizu H
Int J Dermatol 2011 Apr;50(4):439-42. doi: 10.1111/j.1365-4632.2010.04771.x. PMID: 21413955
D'Alessio M, Zambruno G, Charlesworth A, Lacour JP, Meneguzzi G
J Invest Dermatol 2008 Dec;128(12):2815-9. Epub 2008 Jun 19 doi: 10.1038/jid.2008.143. PMID: 18563182
Nakano A, Pulkkinen L, Murrell D, Rico J, Lucky AW, Garzon M, Stevens CA, Robertson S, Pfendner E, Uitto J
Pediatr Res 2001 May;49(5):618-26. doi: 10.1203/00006450-200105000-00003. PMID: 11328943

Recent clinical studies

Etiology

Mutlu M, Kalay E, Dilber B, Aslan Y, Dilber E, Almaani N, McGrath JA
Turk J Pediatr 2015 Jul-Aug;57(4):385-387. PMID: 27186702
Iacovacci S, Cicuzza S, Odorisio T, Silvestri E, Kayserili H, Zambruno G, Puddu P, D'Alessio M
Exp Dermatol 2003 Oct;12(5):716-20. doi: 10.1034/j.1600-0625.2003.00052.x. PMID: 14705814
McMillan JR, McGrath JA, Tidman MJ, Eady RA
J Invest Dermatol 1998 Feb;110(2):132-7. doi: 10.1046/j.1523-1747.1998.00102.x. PMID: 9457907
Niessen CM, van der Raaij-Helmer MH, Hulsman EH, van der Neut R, Jonkman MF, Sonnenberg A
J Cell Sci 1996 Jul;109 ( Pt 7):1695-706. doi: 10.1242/jcs.109.7.1695. PMID: 8832392
Turco AE, Peissel B, Rossetti S, Selicorni A, Manoukian S, Brusasco A, Tadini G, Galimberti A, Tassis B, Turolla L
Am J Med Genet 1993 Dec 1;47(8):1225-30. doi: 10.1002/ajmg.1320470820. PMID: 8291561

Diagnosis

Wee LWY, Tan EC, Bishnoi P, Ng YZ, Lunny DP, Lim HW, Lee SP, Ong C, Yap TL, Mok YH, Low MY, Chu-Tian Chow C, Derrick L, Common JEA, Birgitte Lane E, Koh MJA
Pediatr Dermatol 2021 Jul;38(4):908-912. Epub 2021 Jun 21 doi: 10.1111/pde.14668. PMID: 34152038
Mutlu M, Kalay E, Dilber B, Aslan Y, Dilber E, Almaani N, McGrath JA
Turk J Pediatr 2015 Jul-Aug;57(4):385-387. PMID: 27186702
Stoevesandt J, Borozdin W, Girschick G, Hamm H, Höcht B, Kohlhase J, Volz A, Wiewrodt B, Wirbelauer J
Klin Padiatr 2012 Jan;224(1):8-11. Epub 2011 Sep 26 doi: 10.1055/s-0031-1285877. PMID: 21969027
Lépinard C, Descamps P, Meneguzzi G, Blanchet-Bardon C, Germain DP, Larget-Piet L, Beringue F, Berchel C, Muller F, Dumez Y
Prenat Diagn 2000 Jan;20(1):70-5. doi: 10.1002/(sici)1097-0223(200001)20:1<70::aid-pd747>3.0.co;2-e. PMID: 10701857
Turco AE, Peissel B, Rossetti S, Selicorni A, Manoukian S, Brusasco A, Tadini G, Galimberti A, Tassis B, Turolla L
Am J Med Genet 1993 Dec 1;47(8):1225-30. doi: 10.1002/ajmg.1320470820. PMID: 8291561

Prognosis

Mutlu M, Kalay E, Dilber B, Aslan Y, Dilber E, Almaani N, McGrath JA
Turk J Pediatr 2015 Jul-Aug;57(4):385-387. PMID: 27186702
Stoevesandt J, Borozdin W, Girschick G, Hamm H, Höcht B, Kohlhase J, Volz A, Wiewrodt B, Wirbelauer J
Klin Padiatr 2012 Jan;224(1):8-11. Epub 2011 Sep 26 doi: 10.1055/s-0031-1285877. PMID: 21969027
Dang N, Klingberg S, Rubin AI, Edwards M, Borelli S, Relic J, Marr P, Tran K, Turner A, Smith N, Murrell DF
Acta Derm Venereol 2008;88(5):438-48. doi: 10.2340/00015555-0484. PMID: 18779879
Micheloni A, De Luca N, Tadini G, Zambruno G, D'Alessio M
Br J Dermatol 2004 Oct;151(4):796-802. doi: 10.1111/j.1365-2133.2004.06206.x. PMID: 15491419
Ha D, Idikio H, Krol A, Lin AN
J Cutan Med Surg 1998 Oct;3(2):102-4. doi: 10.1177/120347549800300210. PMID: 9822785

Clinical prediction guides

Stoevesandt J, Borozdin W, Girschick G, Hamm H, Höcht B, Kohlhase J, Volz A, Wiewrodt B, Wirbelauer J
Klin Padiatr 2012 Jan;224(1):8-11. Epub 2011 Sep 26 doi: 10.1055/s-0031-1285877. PMID: 21969027
Dang N, Klingberg S, Rubin AI, Edwards M, Borelli S, Relic J, Marr P, Tran K, Turner A, Smith N, Murrell DF
Acta Derm Venereol 2008;88(5):438-48. doi: 10.2340/00015555-0484. PMID: 18779879
Iacovacci S, Cicuzza S, Odorisio T, Silvestri E, Kayserili H, Zambruno G, Puddu P, D'Alessio M
Exp Dermatol 2003 Oct;12(5):716-20. doi: 10.1034/j.1600-0625.2003.00052.x. PMID: 14705814
Niessen CM, van der Raaij-Helmer MH, Hulsman EH, van der Neut R, Jonkman MF, Sonnenberg A
J Cell Sci 1996 Jul;109 ( Pt 7):1695-706. doi: 10.1242/jcs.109.7.1695. PMID: 8832392

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