Atopic dermatitis is a common disorder that affects 10 to 20 percent of children and 5 to 10 percent of adults.

The genetics of atopic dermatitis are not completely understood. Studies suggest that several genes can be involved in development of the condition. In very rare cases, atopic dermatitis is caused by inherited mutations in a single gene. One such gene is the CARD11 gene. The protein produced from this gene turns on signaling pathways involved in the development and function of immune system cells called lymphocytes. Mutations in the CARD11 gene lead to production of an altered CARD11 protein that does not function normally. These changes impair pathway signaling, and as a result, certain lymphocytes called T cells do not develop or function properly. The number of these cells is normal, but their response to foreign invaders such as bacteria and fungi is diminished. The T cell abnormalities lead to a weakened immune system and recurrent infections, which are common in people with CARD11-associated atopic dermatitis.

It is not clear how the immune dysfunction caused by CARD11 gene mutations leads to skin rashes and allergic disorders in affected individuals. Atopic dermatitis is not initially caused by an allergic reaction, although sometimes substances that can cause allergic reactions (allergens) are thought to contribute to flare-ups of the rashes.

In contrast to rare cases caused by CARD11 gene mutations, most cases of atopic dermatitis are thought to occur due to a combination of genetic and environmental factors (such as living with a pet). Several common genetic variations may be involved, each contributing only a small amount to the risk of developing atopic dermatitis. The strongest of these associations is with the FLG gene, which is altered in 20 to 30 percent of people with atopic dermatitis compared with 8 to 10 percent of the general population without atopic dermatitis.

The FLG gene provides instructions for making a protein called profilaggrin, which is important for the structure of the outermost layer of skin. Proteins derived from profilaggrin help create a strong barrier to keep in water and keep out foreign substances, including toxins, bacteria, and allergens. These proteins also are part of the skin's "natural moisturizing factor," which helps maintain hydration of the outermost layer of skin.

Variations in the FLG gene lead to production of an abnormally short profilaggrin protein that cannot be processed to produce the other profilaggrin-related proteins. The resulting shortage can impair the barrier function of the skin. Impairment of the skin's barrier function contributes to development of allergic disorders, including atopic dermatitis. Research suggests that without a properly functioning barrier, allergens are able to get into the body through the skin, triggering a reaction. In addition, a lack of natural moisturizing factor allows excess water loss through the skin, which can lead to dry skin.

Variations in many other genes are likely associated with development of atopic dermatitis, although most of these genes have not been identified or definitively linked to the disorder. Researchers suspect these genes are involved in the skin's barrier function or in the function of the immune system. However, not everyone with a mutation in FLG or another risk-associated gene develops atopic dermatitis; exposure to certain environmental factors also contributes to the development of the disorder. Studies suggest that these exposures trigger epigenetic changes to the DNA. Epigenetic changes modify DNA without changing the DNA sequence. They can affect gene activity and regulate the production of proteins, which may influence the development of allergies in susceptible individuals.

Syndromes with atopic dermatitis as one of several features are caused by mutations in other genes.