EB can be inherited as the result of a dominant genetic abnormality (only one parent carries the abnormal gene) or a recessive genetic abnormality (both parents carry the abnormal gene).

EB simplex results from mutations in genes responsible for keratin 5 and 14, which are proteins that give cells of the epidermis its structure. EB simplex is transmitted in an autosomal dominant fashion.

Dystrophic EB is caused by mutations in genes for type VII collagen, the protein contained in the fibers anchoring the epidermis to the deeper layers of the skin. The genetic mutations for junctional EB are found in the genes responsible for producing the protein Laminin-5. Dystrophic EB is an autosomal disorder and will only result if both parents transmit an abnormal gene during conception.

EB simplex, the most common form of EB, is the least serious form of the disease. In most affected individuals, the blisters are mild and do not scar after they heal. Some forms of EB simplex affect just the hands and feet. Other forms of EB simplex can lead to more widespread blistering, as well as hair loss and missing teeth. Recurrent blistering is annoying but not life threatening.

The second, or junctional, form of EB does not lead to scarring. However, skin on the areas prone to blistering, such as elbows and knees, often shrinks. In one variation of junctional EB, called gravis junctional EB of Herlitz, the blistering can be so severe that affected infants may not survive due to massive infection and dehydration.

The third form of EB, dystrophic EB, varies greatly in terms of severity, but more typically affects the arms and legs. In one variation, called Hallopeau-Siemens EB, repeated blistering and scarring of the hands and feet causes the fingers and toes to fuse, leaving them dysfunctional and with a mitten-like appearance.