Alexander disease with periventricular calcification: a novel mutation of the GFAP gene

Alexander disease is a rare neurodegenerative leucoencephalopathy caused by de novo mutations in the GFAP gene. Infantile, juvenile, and adult subtypes have been described and the clinical and radiological phenotypes are broad. Here we report on a single case of juvenile-onset Alexander disease associated with a novel frameshift mutation in the GFAP gene. The 8-year-old male patient had a relatively mild clinical phenotype characterized by dystonia, intermittent episodes of raised intracranial pressure, and characteristic radiological changes. He also presented with the additional and to our knowledge previously unreported, neuroimaging finding of periventricular calcification. We postulate that in children with leucoencephalopathy and periventricular calcification of undetermined aetiology, the diagnosis of Alexander disease should be considered. If the magnetic resonance imaging findings are compatible with Alexander disease, then DNA analysis of the GFAP gene should be performed even if the full criteria for a neuroradiological diagnosis are not met.