Spinocerebellar Ataxia 8 (SCA8)

This chapter provides an overview on phenotype, gene function, and diagnosis of spinocerebellar ataxia 8 (SCA8). Spinocerebellar ataxia type 8 (SCA8) patients have a slowly progressive, predominantly cerebellar disease involving dysarthria, limb and gait ataxia, impaired smooth pursuit, and nystagmus. A broad range of other clinical symptoms are also reported, including tremor, spasticity, and various kinds of cognitive impairment. Although this clinical picture is not clearly distinguishable from that of other forms of inherited ataxia, SCA8 is unique among this group of diseases in many ways. The inheritance pattern for SCA8 in particular is the most complicated of all of the inherited spinocerebellar ataxias. SCA8 is caused by a CTG expansion mutation that has been shown to vary widely in size between generations. The SCAB CTG repeat is transcribed as part of a natural, untranslated antisense RNA, but the precise molecular pathogenic mechanism through which this repeat expansion causes disease is currently unknown.