SCA-12: Tremor with cerebellar and cortical atrophy is associated with a CAG repeat expansion

Objective: To characterize the clinical and neuroradiologic features of a n ew spinocerebellar ataxia, SCA-12, in the index family. Background: The aut hors recently linked SCA-12 to a novel CAG repeat expansion on chromosome 5 q31-33 that is located within the 5' region of PPP2R2B, a gene encoding a b rain-specific regulatory subunit of protein phosphatase 2A. Methods: Neurol ogic features of the proband and nine symptomatic relatives in the first SC A-12 family were compiled and, in some individuals, related to changes foun d on brain MRI or CT. Results: SCA-12 typically presented in the 4th decade of life with action tremor of the head or arms (present in 10/10 of the af fected individuals). Hyperreflexia (8/10) was a common feature, and cerebel lar signs (8/10), including ataxia, dysmetria, and dysarthria, developed gr adually but were less prominent and disabling than cerebellar dysfunction i n other SCA. Subtle parkinsonian features (9/10) and dementia (2/10) were o bserved in later stages of SCA-12, and psychiatric symptoms, including depr ession, anxiety, or delusions, were present in some affected family members (4/10). Two individuals studied had nondisabling neurologic signs neonatal ly, including nystagmus and lower extremity dystonia. Brain images of affec ted individuals revealed cerebral and cerebellar atrophy. Conclusions: SCA- 12 is a slowly progressive, autosomal dominant, neurodegenerative disorder that differs from other SCA in that it typically presents with action tremo r in patients in their mid 30s and usually includes hyperreflexia and subtl e parkinsonian signs. Cerebellar dysfunction, including gait ataxia, is rel atively nondisabling, and cognitive or psychiatric disorders may occur. Neu roradiologic studies reveal atrophy of the cerebellum and cerebral cortex.