Article: Incontinentia pigmenti

What is incontinentia pigmenti?

Incontinentia pigmenti is a condition affecting the skin that occurs mainly in females. The disorder is characterized by blistering and wart-like growths followed by changes in skin pigmentation. The condition may also affect the teeth, hair, eyes, and central nervous system.

How common is incontinentia pigmenti?

Incontinentia pigmenti is an uncommon disorder. Between 700 and 1,000 affected individuals have been reported in the scientific literature.

What genes are related to incontinentia pigmenti?

Mutations in the IKBKG gene cause incontinentia pigmenti.

The protein made by the IKBKG gene helps regulate another protein called nuclear factor-kappa-B, which helps protect cells from undergoing programmed cell death (apoptosis) in response to certain signals. In about 80 percent of patients, mutations in the IKBKG gene lead to an abnormally shortened, nonfunctional version of the IKBKG protein. Other patients with incontinentia pigmenti have mutations that cause loss of the IKBKG protein. Without this protein, nuclear factor-kappa-B is not regulated properly, and cells are more likely to undergo apoptosis. Researchers believe that this abnormal cell death leads to the signs and symptoms of incontinentia pigmenti.

How do people inherit incontinentia pigmenti?

This condition is inherited in an X-linked dominant pattern. A condition is considered X-linked if the gene that causes the disorder is located on the X chromosome (one of the two sex chromosomes). The inheritance is dominant if one copy of the altered gene is sufficient to cause the condition. In most cases, males experience more severe symptoms of the disorder than females. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

In some cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.

Research suggests that incontinentia pigmenti occurs mainly in females because males with mutations in the IKBKG gene usually die before birth. Males with these mutations have no functional IKBKG protein. In females with incontinentia pigmenti, only some cells produce normal protein from the IKBKG gene. A lack of functional IKBKG protein in a proportion of cells leads to the signs and symptoms of incontinentia pigmenti in affected females.