Epidermolysis bullosa

Inheritance of epidermolysis bullosa (EB) may be either autosomal dominant or autosomal recessive, depending on the type and subtype of inherited EB present:

• Epidermolysis bullosa simplex (EBS, the most common type of EB) is almost always inherited in an autosomal dominant manner, but rare autosomal recessive forms have been reported.^[1][2]
• Dystrophic epidermolysis bullosa (DEB) can be inherited in an autosomal dominant or autosomal recessive manner, depending on the subtype present. However, dominant DEB is the second most common type of EB.^[1]
• Junctional epidermolysis bullosa is autosomal recessive.^[2]
• Kindler syndrome is autosomal recessive.^[1][2]

A condition is autosomal dominant if having only one changed (mutated) copy of the responsible gene in each cell is enough to cause symptoms of the condition. When a person with an autosomal dominant condition has children, each child has a 50% chance to inherit the mutated copy of the gene. While many people with an autosomal dominant form of EB have a parent with EB, some cases result from a new mutation, occurring for the first time (called a de novo mutation). A person with a de novo mutation still has a 50% chance to pass the mutation on to each of his/her children.

In autosomal recessive inheritance, a person must have a mutation in both copies of the responsible gene in each cell to have EB. Typically, a person with EB inherits one mutated copy of the gene from each parent, who are referred to as carriers. Carriers usually do not have symptoms of the condition. When two carriers of an autosomal recessive condition have children, each child has a 25% chance to be affected, a 50% chance to be an unaffected carrier like each parent, and a 25% chance to not be a carrier and not be affected.

Epidermolysis bullosa acquisita (an acquired form of EB) is a rare autoimmune disorder and is not inherited.

Epidermolysis bullosa (EB) can have either an autosomal dominant or autosomal recessive mode of inheritance in epidermolysis bullosa simplex (EBS) and dystrophic epidermolysis bullosa (DEB). Kindler syndrome and junctional epidermalysis bullosa (with the exception of one report, to our knowledge) are autosomal recessive.^[1][5378] The mode of inheritance in a given family is usually established by analyzing the family history (pedigree analysis).[5378]

EBS in families in which only one child is affected (and the parents are unaffected) could be either autosomal dominant (as the result of a de novo gene mutation) or autosomal recessive. A de novo dominant mutation is the more likely mode of inheritance. The two modes of inheritance can usually be distinguished based on results of immunohistochemistry testing.[5378]

The only accurate method to determine the mode of inheritance in a person with DEB is molecular genetic testing to identify the responsible mutation(s). Symptoms, severity, and other types of lab results alone are not sufficient. Until recently, mutations in the responsible gene were considered 100% penetrant (meaning that all people with mutations would be affected). However in several affected families, a person with a mutation for dominant DEB had no signs of the disease.^[3]

People with questions about the inheritance of their condition and genetic risks to themselves or family members should speak with a genetics professional.

Yes. Differences in severity among affected members of the same family have been reported in EB simplex, dominant dystrophic EB, recessive dystrophic EB, junctional EB, and Kindler syndrome.[5378]^{[3][4][5][6][7]} In some cases, disease severity may be influenced by variations in modifier genes (genes that can alter the expression of another gene) in each affected family member.^[5]

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.