Junctional Epidermolysis Bullosa (ITGB4)
Junctional epidermolysis bullosa (ITGB4-related) is an autosomal recessive disease that is caused by pathogenic variants in the ITGB4 gene. This disease can be divided into two forms, known as the non-Herlitz type and epidermolysis bullosa with pyloric atresia (EB-PA). EB-PA is more severe and is typically lethal in infancy. Clinical features of both types include fragile skin and mucous membranes that are prone to blistering. In the EB-PA type, blisters may be present at birth and can lead to frequent infections, electrolyte imbalances, and blood loss. Blisters also occur in the mouth, airway, eyes, and bladder. Recurrent cycles of blistering and healing lead to narrowing of the airway, which may be fatal. Infants are typically born with a blockage of the lower part of the stomach that causes vomiting, distended abdomen, and absence of stool. Pyloric atresia is life-threatening and must be repaired with surgery soon after birth. In the non-Herlitz type, blistering is milder and may be localized to certain parts of the body. Some patients do not experience blistering after the newborn period. Some patients may also have abnormalities of the nails and hair. Life expectancy is reduced to the first year of life for infants with EB-PA, but is usually normal in patients with the non-Herlitz type. Pathogenic variants in the gene ITGB4 can also cause an autosomal dominant condition called epidermolysis bullosa of hands and feet, characterized by localized pattern of blistering primarily on the hands and feet. No clear genotype-phenotype correlation has been established.
For information about carrier frequency and residual risk, please see the residual risk table.