Late-onset pure cerebellar ataxia: differentiating those with and without identifiable mutations

Late onset cerebellar ataxia can be caused by several genetic mutations but a large percentage of patients remain undiagnosed. Thirty-eight patients with onset of slowly progressive, pure cerebellar ataxia >or=40 years-of-age were identified from a large ataxia database. Their clinical findings and quantitative oculomotor tests were reviewed; all were screened for SCA1, SCA2, SCA3, SCA6, SCA8, SCA14, and the Fragile X premutation (FMR1). All 47 exons of CACNA1A were screened for mutations. Genetic analysis uncovered a mutation in 11 patients. The SCA6 mutation was present in 8 patients (repeats 22-23). Three additional genetic mutations were found: SCA1 (42 repeats), SCA3 (66 repeats), and SCA8 (121 repeats). Patients without identified genetic mutations were characterized by 1) a later age of onset, 2) truncal without extremity ataxia, 3) and down beat nystagmus. Although only a third of these idiopathic late onset ataxia patients had a positive family history, this homogeneous syndrome probably represents a yet to be identified genetic disorder.