What is Aicardi Syndrome

Aicardi syndrome is a rare neurologic disorder first described by the French neurologist, Dr. Jean Aicardi, in 1965. It occurs almost exclusively in females (46,XX), however, it can also occur in males with Klinfelter Syndrome (47,XXY).  A handful of reports in the literature exist of Aicardi syndrome in a normal male. Some of these reports have been disputed, and it is possible that these cases are caused by mosaic mutations of the Aicardi syndrome gene(s).

What Causes Aicardi Syndrome

The genetic basis or mutation which causes Aicardi syndrome has not been identified despite the efforts of several laboratories worldwide and genetic sequencing of affected children and their parents.  Because Aicardi syndrome occurs only in a single member of a family, and virtually all cases are female, the genetic mutation is thought to be a dominant de novo (i.e., spontaneous) mutation in an X-linked gene with lethality in normal (46,XY) males. There are at least 6 sets of twins that are discordant for Aicardi syndrome, and one known set of monozygotic twins and one pair of non-twin sisters that are both affected. Aicardi syndrome in the non-twin sisters is likely due to chance since there have been no other reports of Aicardi syndrome in two siblings.

Features of Aicardi Syndrome

Aicardi syndrome is classically defined in over 90% of cases by three cardinal features:

In 1999, the diagnostic spectrum of Aicardi syndrome was broadened to include patients with present, but usually abnormal, corpus callosum or absence of infantile spasms or lacunae, if other typical brain abnormalities are present. Specifically, the revised criteria were expanded to include two classic features plus at least two other major or supporting features. Retinal lacunae and seizures are present in all, or almost all, of the cases.  Major and supporting features include:

Major Features

Supporting Features

Involvement of other organ systems besides the brain and eyes are also common but the signs and symptoms are not part of the diagnostic criteria and are not present in all cases. These include:

It is generally accepted that the number and severity of features present in a child with Aicardi syndrome is associated with the individual prognosis.