A 24bp duplication mutation in exon 2 of the ARX gene has been identified in a 72 year old man with X-linked mental retardation, a spastic ataxic gait, and dystonia of hand and facial muscles. MRI examination showed cerebrospinal fluid filled cystic cavities surrounded by gliosis in both cerebral and cerebellar hemispheres.

As the cysts were lying at the outer margins of the brain substance, infarcts were considered as a cause but the largest lesion was too extensive to represent small vessel occlusion. In addition, the lesions were outside the watershed area and there was no surrounding parenchymal retraction.

The patient had no history of acute neurological impairment and no identifiable risk factors for cerebrovascular disease. Other members of his family had various neurological impairments including infantile spasms, epilepsy, spasticity, and cerebellar ataxia. One relative had bilateral cerebral and cerebellar cysts.

The investigators conclude the most likely explanation for the cystic cavities are abnormalities of the developing fetal brain caused by the ARX mutation. The gene is widely expressed in the brain and has been shown to play an important role in neuronal proliferation and interneuronal migration and proliferation in a knockout mouse model.