Clinical, cytogenetic, and pedigree findings in 18 cases of Aicardi syndrome

Eighteen girls with Aicardi syndrome were identified through a survey of neurologists, geneticists, and ophthalmologists. All had infantile seizures, developmental delay, agenesis of the corpus callosum (complete: 72%, partial: 28%), and characteristic chorioretinal lacunar lesions. Costovertebral defects including hemivertebrae, scoliosis, and absent or malformed ribs were present in 39%, cortical heterotopias were present in 50%, and microphthalmia was identified in a third. Cytogenetic investigation was carried out in all families. An unbalanced X;3 translocation, 46,X,der(X)t(X;3)(p22.3;p23)mat, was discovered in a girl with chorioretinal lacunar lesions characteristic of Aicardi syndrome, developmental delay, and infantile seizures. However, this child had a normal appearing corpus callosum on CT and magnetic resonance imaging scans and therefore did not meet the criteria for inclusion in the study. Chromosomes of all other patients and parents were normal. Findings at birth, age of seizure onset, treatment, and prognosis are discussed. The pedigree data from these 18 families demonstrated an unaffected male:female sib ratio of 1:1.7 and a 14% spontaneous abortion rate. The findings of this study support the contention that Aicardi syndrome is an X-linked dominant disorder with early embryonic lethality in hemizygous males and that all cases represent new mutations.