Epidermolysis bullosa (EB) is almost always caused by a genetic mutation that makes the skin extremely fragile. In rare conditions, it’s not inherited but is caused by the immune system.
Genetic causes of EB include the presence of a defective (or mutated) gene that is inherited from one or both parents, or it occurs as a spontaneous mutation, making the child the first in the family to have the disease.
Non-genetic reasons for EB a type that results from the immune system attacking the body’s healthy tissue by mistake.
In the majority of cases, patients inherit the defective gene causing EB from one or both parents. Different types of EB are caused by mutations in different genes that are involved in the formation of skin layers – the epidermis (outer layer), the dermis (underlying layer), and the basement membrane zone (the area where the dermis and epidermis meet).
An individual’s DNA contains coding sequences called genes, which provide the information necessary to make proteins in different parts of the body, including the skin. Every gene exists as a pair, each inherited from one parent.
The faulty genes causing EB can be inherited in two ways – autosomal recessive and autosomal dominant.
Autosomal recessive inheritance
In this case, both copies of the gene are defective. Therefore, autosomal recessive EB develops if an individual inherits a defective copy of a gene from their mother and the second defective copy from their father. The parents are said to be carriers — they each carry one defective copy of the gene, but its effect is compensated or masked by the other normal copy, so they do not exhibit symptoms of the skin disorder themselves. When both parents are carriers, there is a 25 percent chance of their child developing the condition.
Junctional EB, caused by defects in the genes that promote the formation of anchoring fibrils (fibers that attach the epidermis to the basement membrane) or hemidesmosomes (a structure found on the basal surface of skin cells), is inherited in an autosomal recessive manner.
Autosomal dominant inheritance
In this case, a defect (mutation) in one of the copies of a gene is enough for EB to develop. Thus, autosomal dominant EB develops if an individual inherits the defective gene from just one parent. Since the defective copy of the gene dominates the effect of the normal copy, the parent carrying the faulty gene also has the condition. In autosomal dominant inheritance, there is a 50 percent chance that a child will develop EB.
Epidermolysis bullosa simplex (EBS), caused by defects in the gene coding for keratin (a protein in the outer skin layer), is usually inherited as an autosomal dominant disease.
Dystrophic EB, caused by defects in the gene coding for type VII collagen protein (a major structural component of the anchoring fibrils), can be inherited in both recessive and dominant ways.
EB can also be caused by mutations in a gene that occur during the formation of the egg or sperm cells in a parent. In such a case, neither parent is a carrier of a faulty gene, but the child still develops the disease. Since the spontaneous mutation in one of the alleles dominates the normal allele, the defective allele is inherited by the patient’s children in an autosomal dominant manner.
In this case, the body produces antibodies (proteins that act against foreign substances) against its own molecules causing autoimmune disorders. Epidermolysis bullosa acquisita (EBA) is a rare autoimmune disorder in which the body develops antibodies against its own anchoring fibrils.
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