Alexander Disease: New Insights From Genetics

Abstract
In 1949, W. S. Alexander described a boy who died at 16 months of age with a history of megalencephaly, hydrocephalus, and psychomotor retardation (1). A striking feature of the pathology in this case was the accumulation of Rosenthal fibers within astrocytes and an associated degeneration or failure of myelination. During the ensuing 15 yr, several similar patients were reported and given such descriptive diagnoses as fibrinoid degeneration of astrocytes, dysmyelinogenic leukodystrophy, fibrinoid leukodystrophy, and megalencephaly with hyaline panneuropathy. When Friede described the sixth case in 1964, he coined the eponym Alexander disease to refer to this fascinating but mysterious childhood disease (2).