Rett syndrome: cerebellar pathology. The cerebellar pathology at autopsy of 5 patients with Rett syndrome is described. The patients ranged in age from 7-30 years. All had markedly reduced brain weights with proportionately small cerebella. Microscopic examination revealed loss of Purkinje cells, atrophy, astrocytic gliosis of the molecular and granular cell layers, and gliosis and loss of myelin in the white matter. Cortical atrophy occurred focally along the folia and was often more marked in the tips of the folia. The 2 oldest patients had been treated with phenytoin which may have contributed to the morphologic changes. Atrophy and gliosis increased with age or in patients without phenytoin treatment; the youngest patient demonstrated only minor microscopic changes. In addition to the generalized alterations, 1 patient had several adjacent folia with severe atrophy. The results indicate that cerebellar changes in Rett syndrome consist of general hypoplasia with the addition of atrophy beginning in childhood and progressing over many years. 