ON AN AUTOSOMAL-DOMINANT FORM OF RETINAL-CEREBELLAR DEGENERATION - ANAUTOPSY STUDY OF 5 PATIENTS IN ONE FAMILY

We describe a family with an autosomal dominant form of retinal-cerebe llar atrophy. There is an extreme variability in age of onset and seve rity of the clinical symptoms: some patients remain nearly asymptomati c throughout their entire life; others develop severe retinal and cere bellar symptoms after the age of 35 years; others suffer from a severe disorder with onset in adolescence and death during the third decade of life; in others the onset is in early childhood with prevalence of cerebellar symptoms. There is neither dementia nor epilepsy in any of the patients. Four out of five autopsies showed, a severe retinal atro phy, and all five autopsies were also characterized by (1) a cerebella r atrophy affecting the spinocerebellar and olivocerebellar tracts, th e cerebellar cortex and the efferent cerebellar pathways, (2) an invol vement of the pyramidal pathways and of the motor neurons of brain ste m and spinal cord, and (3) an atrophy of the subthalamic nucleus and t o a much lesser extent of the pallidum, with also some damage to the s ubstantia nigra. The posterior columns are much less affected except i n one patient. In this family, we have excluded linkage with the two l oci for spinocerebellar ataxia, i.e., SCA1 on chromosome 6p and SCA2 o n chromosome 12q as well as with the locus for Machado-Joseph disease (MJD) on chromosome 14q. A genome-wide search is currently being perfo rmed to detect the disease locus responsible.