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.
Kerber
Kevin A
KA
Department of Neurology, UCLA School of Medicine, Los Angeles, CA, USA.
Jen
Joanna C
JC
Perlman
Susan
S
Baloh
Robert W
RW
D000328:Adult; D017668:Age of Onset; D000368:Aged; D003937:Diagnosis, Differential; D005190:Family; D005260:Female; D005600:Fragile X Syndrome / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology; D009154:Mutation / Q000235:genetics* / Q000502:physiology*; D009759:Nystagmus, Pathologic / Q000209:etiology / Q000503:physiopathology; D009801:Oculomotor Muscles / Q000503:physiopathology; D013132:Spinocerebellar Degenerations / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology