Aicardi Syndrome Genetics

Aicardi syndrome is a rare genetic condition that almost exclusively affects females. The condition is characterized by a partial or complete absence of an important brain structure called the corpus callosum, which connects the two halves of the brain.

As Aicardi syndrome mainly affects females, experts believe the condition arises due to a mutation on the X chromosome. In healthy individuals, 46 chromosomes exist in each cell, two of which are the sex chromosomes (X and Y). Females usually have two X chromosomes, while males usually have one X and one Y chromosome

Aside from determining a person’s sexual characteristics, genes located on the sex chromosomes are also involved in other bodily functions. During the early stages of embryonic development in females, one of the X chromosomes is inactivated in cells of the body that are not the germ cells (sperm or egg cells). This inactivation of one X chromosome means that like males, females only have one active X chromosome in each of their body cells. This inactivation usually happens randomly, with each X chromosome therefore active in around half of all body cells.

However, on some occasions, this inactivation is not random, which is referred to as skewed X-inactivation. This occurs when there is a mutation present in one of the X chromosomes found in each cell. This skewed X-inactivation has been found to occur in females that have Aicardi syndrome, which provides further evidence to support that the theory that this condition arises as a result of an X chromosome mutation. However, the gene in question has not yet been identified and exactly how the mutation leads to symptoms of the disorder is not  known.

Almost all cases of Aicardi syndrome have occurred sporadically, meaning the condition is not inherited through the generations and can occur randomly in people with no family history of the disease. The condition is therefore believed to arise as the result of new mutations.

In females, the mutation present on one X chromosome is enough to cause symptoms of Aicardi syndrome. If the mutation occurs in males with only one X chromosome, it is lethal very early on in embryonic development, meaning that usually only females are born with the condition. In the few cases where males have been affected by Aicardi syndrome, they have carried an extra X chromosome (XXY), a condition know of as Klinefelter's syndrome.