EB-PA appears to be a rare condition, although its prevalence is unknown. At least 100 affected individuals have been reported worldwide.

EB-PA can be caused by mutations in the ITGA6, ITGB4, and PLEC genes. These genes provide instructions for making proteins with critical roles in the skin and digestive tract.

ITGB4 gene mutations are the most common cause of EB-PA; these mutations are responsible for about 80 percent of all cases. ITGA6 gene mutations cause about 5 percent of cases. The proteins produced from the ITGA6 and ITGB4 genes join to form a protein known as α6β4 integrin. This protein plays an important role in strengthening and stabilizing the skin by helping to attach the top layer of skin (the epidermis) to underlying layers. Mutations in either the ITGA6 gene or the ITGB4 gene lead to the production of a defective or nonfunctional version of α6β4 integrin, or prevent cells from making any of this protein. A shortage of functional α6β4 integrin causes cells in the epidermis to be fragile and easily damaged. Friction or other minor trauma can cause the skin layers to separate, leading to the formation of blisters.

About 15 percent of all cases of EB-PA result from mutations in the PLEC gene. This gene provides instructions for making a protein called plectin. Like α6β4 integrin, plectin helps attach the epidermis to underlying layers of skin. Some PLEC gene mutations prevent the cell from making any functional plectin, while other mutations result in an abnormal form of the protein. When plectin is altered or missing, the skin is less resistant to friction and minor trauma and blisters easily.

Researchers are working to determine how mutations in the ITGA6, ITGB4, and PLEC genes lead to pyloric atresia in people with EB-PA. Studies suggest that these genes are important for the normal development of the digestive tract.