In a nation-wide survey of Aicardi syndrome, defined as the onset of epilepsy in the first six months of life, agenesis of the corpus callosum (partial or total) and lacunar chorioretinopathy, 18 patients, all girls, born between 1975 and 2002 were identified in Sweden. Fifteen were definite cases and three were regarded as probable, since they only fulfilled two of three inclusion criteria in addition to other cerebral malformations and/or chorioretinal changes. Calculations based on this survey and population-based studies on epilepsy in retarded children yielded a prevalence rate in the range of 2 - 15 : 100 000 girls. All but one had an ordinary birth weight, length and head circumference for gestational age. One was born preterm, one post term. The age at diagnosis varied from three days to 12 years and decreased during the period reflecting the increased awareness of the syndrome. Eleven came to medical attention because of seizures. Six had myoclonic, four generalized tonic-clonic and eight tonic, clonic or complex partial seizures. One had hypsarrhythmia, five multifocal epileptiform activity, three bilateral independent bursts, two burst-suppression pattern, six other types of spikes and one slowing of background activity. Asymmetrical EEG abnormalities indicating independent hemispheric dysfunction were detected in 13/18 (72 %). Complete absence of the corpus callosum was found in 13/18 (72 %), although not identical with the previous group, a partial defect in 3/18 (17 %), and a thinning in 2/18 (11 %). Of 15 children with definite Aicardi syndrome, 13 had binocular and two monocular lacunae. In one of the latter two, subtle monocular lacunae were found on fundus photographs, but had been missed on repeated clinical examinations. Of three children with probable Aicardi syndrome typical lacunae were reported in one and other kinds of depigmentation in the other two. Most of the children had anomalous optic discs. Neuroimaging in infancy or early childhood combined with ophthalmological examination and ocular fundus photography will facilitate an early diagnosis of Aicardi syndrome. Seizure type and EEG abnormalities may be non-specific at onset.

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Aicardi syndrome has been defined by the triad of agenesis of the corpus callosum, early seizure onset and lacunar chorioretinopathy. In a nation-wide survey a total of 18 Swedish cases were found. Fourteen girls were re-examined by one of the authors at the ages of 1-27 years. One was seizure free following epilepsy surgery operation, 13 were drug resistant. Two were on ketogenic diet. Most of the girls had multifocal EEG discharges. All except one were severely disabled with severe mental retardation and total dependency on helpers for activities of daily life. Communication, nutrition, and motor function were severely affected areas. Visual function was difficult to evaluate because of mental retardation and lack of co-operation and varied from severely impaired to normal. In one case the appearance of the ocular fundus was documented to have changed with time. One girl was exceptional and seizure free with mild mental retardation. An update by March 2006 showed that 12/18 patients were still alive, at a median age of 13.5 years (range: 3-31 years). Six had died between the ages of 3-10 years. They had all suffered from intractable epilepsy and belonged to the most disabled group. Surprisingly two had died from malignant brain tumours.

An eight-year-old girl with Aicardi syndrome (AIC) developed signs of increased intracranial pressure. A clinical and radiological investigation revealed a tumor in the posterior fossa, which was resected. The histopathological diagnosis was large-cell medulloblastoma. Eight months later, she died of a local recurrence, despite treatment with chemotherapy and radiotherapy according to a PNET protocol. In addition to the growth of a large-cell medulloblastoma at the location of the primary tumor and the meningeal spread of the tumor, the autopsy revealed major cortical and subcortical malformations of the brain. Various benign (e.g., plexus papillomas) and malignant tumors (angiosarcoma, embryonic carcinoma, and hepatoblastoma) have been reported in connection with Aicardi syndrome. A genetic analysis of AIC suggests that the mutation is localized on the distal part of the short arm of the X chromosome, an area that may be of importance for tumor development. This is the first report of a primary malignant brain tumor -- large-cell medulloblastoma -- in a patient with Aicardi syndrome.