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Epidermolysis bullosa, junctional 6, with pyloric atresia(JEB6)

MedGen UID:
1803348
Concept ID:
C5676957
Disease or Syndrome
Synonyms: EPIDERMOLYSIS BULLOSA, JUNCTIONAL 6, WITH PYLORIC ATRESIA; JEB6
 
Gene (location): ITGA6 (2q31.1)
 
Monarch Initiative: MONDO:0859233
OMIM®: 619817

Disease characteristics

Excerpted from the GeneReview: Epidermolysis Bullosa with Pyloric Atresia
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; renal and/or ureteral anomalies; and protein-losing enteropathy. The course of EB-PA is usually severe and most often lethal in the neonatal period. Those who survive may have severe blistering with formation of granulation tissue on the skin around the mouth, nose, diaper area, 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 epidermolysis bullosa (EB) include congenital localized absence of skin (aplasia cutis congenita) affecting the extremities and/or head, milia, nail dystrophy, scarring alopecia, hypotrichosis, and corneal abnormalities. [from GeneReviews]
Authors:
Anne W Lucky  |  Emily Gorell   view full author information

Additional descriptions

From OMIM
Junctional epidermolysis bullosa-6 with pyloric atresia (JEB6) is an autosomal recessive blistering disease of skin and mucous membranes. Pyloric atresia is usually evident within a few days of life. Full thickness skin loss (aplasia cutis congenita) may also occur. The plane of skin cleavage is through the lamina lucida of the cutaneous basement membrane zone. JEB5B is usually lethal within the first few weeks of life despite surgical correction of pyloric atresia (summary by Has et al., 2020). Another form of junctional epidermolysis bullosa with pyloric atresia (JEB5B; 226730) is caused by mutation in the integrin-beta-4 gene (ITGB4; 147557). See also epidermolysis bullosa simplex with pyloric atresia (EBS5C; 612138), which is caused by mutation 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.  http://www.omim.org/entry/619817
From MedlinePlus Genetics
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.

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.

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.

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.  https://medlineplus.gov/genetics/condition/epidermolysis-bullosa-with-pyloric-atresia

Clinical features

From HPO
Esophageal stenosis
MedGen UID:
5026
Concept ID:
C0014866
Disease or Syndrome
An abnormal narrowing of the lumen of the esophagus.
Congenital pyloric atresia
MedGen UID:
870867
Concept ID:
C4025327
Congenital Abnormality
Congenital atresia of the pylorus.
Microtia
MedGen UID:
57535
Concept ID:
C0152423
Congenital Abnormality
Underdevelopment of the external ear.
Oral mucosal blisters
MedGen UID:
208888
Concept ID:
C0853945
Sign or Symptom
Blisters arising in the mouth.
Aplasia cutis congenita of scalp
MedGen UID:
343411
Concept ID:
C1855698
Congenital Abnormality
A developmental defect resulting in the congenital absence of skin on the scalp.
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.

Professional guidelines

PubMed

Pfendner EG, Nakano A, Pulkkinen L, Christiano AM, Uitto J
Prenat Diagn 2003 Jun;23(6):447-56. doi: 10.1002/pd.619. PMID: 12813757

Recent clinical studies

Etiology

Raboei E, Alabdali A, Owiwi Y, Yousef Y, Alsaggaf A, Bustanji N, Ghallab A, Bakheet K, Altaf A
J Pediatr Surg 2021 Dec;56(12):2392-2398. Epub 2021 Jun 5 doi: 10.1016/j.jpedsurg.2021.05.023. PMID: 34215433
Ashton GH, Sorelli P, Mellerio JE, Keane FM, Eady RA, McGrath JA
Br J Dermatol 2001 Feb;144(2):408-14. doi: 10.1046/j.1365-2133.2001.04038.x. PMID: 11251584
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
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
Brown TA, Gil SG, Sybert VP, Lestringant GG, Tadini G, Caputo R, Carter WG
J Invest Dermatol 1996 Sep;107(3):384-91. doi: 10.1111/1523-1747.ep12363370. PMID: 8751975

Diagnosis

Martinez-Moreno A, Ocampo-Candiani J, Alba-Rojas E
Pediatr Dermatol 2020 Sep;37(5):821-826. Epub 2020 Jul 20 doi: 10.1111/pde.14245. PMID: 32686866
Verma KP, Robertson SJ, Winship IM
Clin Exp Dermatol 2020 Aug;45(6):793-795. Epub 2020 May 2 doi: 10.1111/ced.14223. PMID: 32359087
Mencía Á, García M, García E, Llames S, Charlesworth A, de Lucas R, Vicente A, Trujillo-Tiebas MJ, Coto P, Costa M, Vera Á, López-Pestaña A, Murillas R, Meneguzzi G, Jorcano JL, Conti CJ, Escámez Toledano MJ, del Río Nechaevsky M
Exp Dermatol 2016 Apr;25(4):269-74. Epub 2016 Feb 13 doi: 10.1111/exd.12938. PMID: 26739954
Pfendner EG, Nakano A, Pulkkinen L, Christiano AM, Uitto J
Prenat Diagn 2003 Jun;23(6):447-56. doi: 10.1002/pd.619. PMID: 12813757
Ashton GH, Sorelli P, Mellerio JE, Keane FM, Eady RA, McGrath JA
Br J Dermatol 2001 Feb;144(2):408-14. doi: 10.1046/j.1365-2133.2001.04038.x. PMID: 11251584

Prognosis

Raboei E, Alabdali A, Owiwi Y, Yousef Y, Alsaggaf A, Bustanji N, Ghallab A, Bakheet K, Altaf A
J Pediatr Surg 2021 Dec;56(12):2392-2398. Epub 2021 Jun 5 doi: 10.1016/j.jpedsurg.2021.05.023. PMID: 34215433
Martinez-Moreno A, Ocampo-Candiani J, Alba-Rojas E
Pediatr Dermatol 2020 Sep;37(5):821-826. Epub 2020 Jul 20 doi: 10.1111/pde.14245. PMID: 32686866
Mencía Á, García M, García E, Llames S, Charlesworth A, de Lucas R, Vicente A, Trujillo-Tiebas MJ, Coto P, Costa M, Vera Á, López-Pestaña A, Murillas R, Meneguzzi G, Jorcano JL, Conti CJ, Escámez Toledano MJ, del Río Nechaevsky M
Exp Dermatol 2016 Apr;25(4):269-74. Epub 2016 Feb 13 doi: 10.1111/exd.12938. PMID: 26739954
Allegra M, Gagnoux-Palacios L, Gache Y, Roques S, Lestringant G, Ortonne JP, Meneguzzi G
J Invest Dermatol 2003 Dec;121(6):1336-43. doi: 10.1111/j.1523-1747.2003.12625.x. PMID: 14675179
Ashton GH, Sorelli P, Mellerio JE, Keane FM, Eady RA, McGrath JA
Br J Dermatol 2001 Feb;144(2):408-14. doi: 10.1046/j.1365-2133.2001.04038.x. PMID: 11251584

Clinical prediction guides

Raboei E, Alabdali A, Owiwi Y, Yousef Y, Alsaggaf A, Bustanji N, Ghallab A, Bakheet K, Altaf A
J Pediatr Surg 2021 Dec;56(12):2392-2398. Epub 2021 Jun 5 doi: 10.1016/j.jpedsurg.2021.05.023. PMID: 34215433
Pfendner EG, Nakano A, Pulkkinen L, Christiano AM, Uitto J
Prenat Diagn 2003 Jun;23(6):447-56. doi: 10.1002/pd.619. PMID: 12813757
Pulkkinen L, Kurtz K, Xu Y, Bruckner-Tuderman L, Uitto J
Lab Invest 1997 Jun;76(6):823-33. PMID: 9194858
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
Smith LT
Arch Dermatol 1993 Dec;129(12):1578-84. PMID: 7504435

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