Congenital olivopontocerebellar atrophy: report of two siblings with paleo- and neocerebellar atrophy.

We report two sisters with congenital olivopontocerebellar atrophy, including immunohistochemical studies of autopsy brain tissue. Both cases showed microcephaly with disproportionately marked hypoplasia of the posterior fossa structures including pons, inferior olivary nuclei, and cerebellum. Microscopically, the pons was atrophic with near total loss of pontine nuclei and transverse pontocerebellar tracts (inferior and middle cerebellar peduncles). The medulla showed absent inferior olivary and arcuate nuclei. The cerebellum showed hypoplasia with rudimentary dentate nuclei, profound loss of Purkinje cells and external granule cell layer, a sparse internal granule cell layer of the entire dorsal vermis and the dorsal portions of the lateral folia, as well as markedly reduced underlying axon fibers in the white matter with marked astrogliosis. These features were highlighted by immunohistochemical study using antibodies against Purkinje cell epitopes, synaptophysin, neurofilament, glial fibrillary acidic protein, and tuberin. The cerebral hemispheres were unremarkable. Our cases are characterized by a pattern of diffuse posterior cerebellar involvement that has rarely been described in previous reports. An autosomal recessive pattern of inheritance is suggested. The abnormalities may result from antenatal degeneration or atrophy of neurons in the involved sites rather than hypoplasia or developmental arrest starting in the second and third month of late embryonic life.