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Junctional epidermolysis bullosa-pyloric atresia syndrome
Junctional epidermolysis bullosa with pyloric atresia is a severe subtype of junctional epidermolysis bullosa (JEB, see this term) characterized by generalized blistering at birth and congenital atresia of the pylorus and rarely of other portions of the gastrointestinal tract.
Prevalence is unknown. More than 100 cases have been reported worldwide.
Skin manifestations include severe blistering, atrophic scarring, and nail dystrophy. Congenital absence of skin (aplasia cutis congenita) is present in approximately 20% of cases, and ear anomalies are also relatively common. The manifestations of pyloric atresia include vomiting, abdomen distension, and an absence of stools. Patients present oral cavity involvement and enamel hypoplasia. Other extracutaneous manifestations include involvement of the respiratory, gastrointestinal and genitourinary tracts. In particular, genitourinary malformations and acquired genitourinary abnormalities (polypoid bladder wall lesions, hemorrhagic cystitis, urethral strictures) are relatively frequent and characteristic. Growth delay and anemia, secondary to the extensive cutaneous and mucosal lesions, are common. Polyhydramnios, secondary to pyloric atresia, is usually present in pregnancies with an affected fetus. Some patients with an identical presentation have been found to have intraepidermal rather than intra-lamina lucida blister formation, necessitating their inclusion under the rarer subtypes of EB simplex rather than under junctional EB.
The condition is caused by mutations in either of the genes encoding the two subunits of alpha6-beta4 integrin, ITGA6 (2q31.1) and ITGB4 (17q11-qter).
Diagnosis in neonates is suspected based on clinical findings of skin fragility and gastric outlet obstruction. In addition to the finding of a cleavage plane located within the lamina lucida of the cutaneous basement membrane zone by immunofluorescence antigen mapping and/or transmission electron microscopy, a negative or highly reduced immunofluorescence staining for integrin alpha6beta4 is typical of JEB-PA. Genetic testing is possible but is not necessary to confirm the diagnosis.
For pregnancies at risk, genetic testing for prenatal diagnosis is required if the disease-causing mutations have been identified in the family.
The condition follows an autosomal recessive pattern of inheritance.
Management and treatment
Pyloric atresia must be corrected surgically.
JEB-PA leads in most cases to early death. Prognosis depends predominantly on the prompt surgical correction of pyloric atresia. Among patients in whom this is successful, a minority show mild skin involvement or a gradual improvement of blistering lesions and survive until adulthood.
- Summary information
- Russian (2012, pdf)
- Emergency guidelines
- Français (2012, pdf)
- Anesthesia guidelines
- English (2011, pdf)
- Review article
- English (2010)
- Clinical genetics review
- English (2017)