Investigators at University Hospital of Bonn and 13 other centers in Germany, France, and Italy conducted a prospective, longitudinal observational study (2008-2011) of offspring or siblings of patients with spinocerebellar ataxias (SCA)-1, 2, 3, and 6. Study individuals had no ataxia and were aged 18-50 years (35-70 years, if directly related to individuals with SCA6). Relations between outcome variables and time from onset (present age to estimated age at ataxia onset) were analyzed using clinical scales, questionnaires, and coordination tests. In 264 participants, estimated time to ataxia from onset was -9 years in 50 carriers of the SCA1 mutation, -12 years in 312 SCA2 mutation carriers, -8 years in 26 SCA3 mutation carriers, and -18 years in 16 SCA6 mutation carriers. Compared with non-carriers of each mutation, SCA1 and SCA2 mutation carriers had higher median scores for ataxia. SCA2 carriers had lower functional index scores than did non-carriers and worse composite cerebellar functional scores than did their non-carrier counterparts. In 83 individuals (30%) who underwent MRI, brainstem and cerebellum showed grey-matter loss in SCA1 and SCA2 mutation carriers. 
COMMENT. The authors summarize the baseline findings of the RISCA study designed to define the preclinical stages of SCAs in individuals at risk and to identify functional and brain structural abnormalities before the onset of ataxia. Carriers of SCA1 and SCA2 mutations have mild coordination functional deficits and brain structural abnormalities before the onset of clinically manifest ataxia. Recognition of the preclinical manifestations of neurodegenerative diseases may permit early therapeutic intervention.
Infantile onset spinocerebellar ataxia. Identification of a novel Twinkle mutation is reported in a family with infantile onset spinocerebellar ataxia in two individuals manifesting ataxia, peripheral sensory neuropathy, athetosis, seizures, deafness, and ophthalmoplegia.