The spinocerebellar ataxias (SCAs) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by limb and gait ataxia. More than 25 different types of SCA have been described, although the causative genes have not yet been identified for all types. Unlike other SCA disorders in which the first symptom is generally ataxia, SCA type 12 (SCA12) typically presents with action tremor involving the upper extremities. It then progresses to include signs of cerebellar dysfunction, such as ataxia, dysarthria (slow, distorted speech), and oculomotor disorders. In addition, SCA12 patients may exhibit hyperreflexia, hypertonia, and mild Parkinsonian symptoms, including bradykinesia (slowed movement) and rigidity. Dementia, psychiatric disorders, and urinary incontinence are also possible. Although variable, the patient age at disease onset is
typically in the fourth decade of life. SCA12 is caused by expansion of a CAG trinucleotide repeat in the PPP2R2B gene located on chromosome 5 at band q32. This expansion is in a noncoding region of the gene; therefore, it is not translated into a polyglutamine tract within the protein, as is seen with other types of SCA.