A severe case of Aicardi syndrome with triple X

Aicardi syndrome is characterized by the combination of partial or total agenesis of the corpus callosum, chorioretinal lacunae and infantile spasms. Genetically, patients exhibit alterations in the Xp22.1–22.3 locus, resulting in lethality of males and development of Aicardi syndrome in females.

We report a severe case of Aicardi syndrome in a girl with complete

triple X chromosome anomaly showing drug resistent infantile spasms, various brain malformations including agenesis of the corpus callosum, stenogyria, polymicrogyria, heterotopia, multiple cysts and malformations of the cerebellum, the hypothalamus, limbic system and the brainstem. Signs of significant myelinization were absent. EEG findings include multifocal epileptic activity with hypsarrhythmia. A haemangioma on the left upper lid, left-sided ptosis and supranuclear facial nerve palsy were also found. Midline defects consisted in vertebral anomalies and a muscular ventricular septal defect. Clinically, there was almost complete absence of development of cognitive and motor functions at the age of 7 months.

Chromosome analysis showed a complete 47, XXX constellation excluding a mosaic type pattern. Detailed analysis using microsatellite markers revealed 3 different X-chormosomes, two of maternal and one of paternal origin. Sequencing of the ARX locus as a candidate gene for Aicardi syndrome did not show any significant pathologic findings. However an already described polymorphism was found in this position.

We suggest that the non-mosaic triple X-anomaly escapes the mechanism of random or skewed inactivation by lyonization. This results in the ubiquitous presence of at least one dominant mutant gene leading to an aggravation of symptomes of Aicardi syndrome and extremely poor prognosis.