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Spinocerebellar ataxia type 6: genotype and phenotype in Germankindreds |
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| Authors: | L. Schols R. Kruger G. Amoiridis H. Przuntek J. Epplen O. Riess |
| Affiliation: | Department of Neurology, St Josef Hospital, Ruhr-University, Bochum, Germany. |
| Abstract: | OBJECTIVE—Spinocerebellar ataxia type 6 (SCA6) isan autosomal dominant cerebellar ataxia (ADCA) of which the mutationcausing the disease has recently been characterised as an expanded CAGtrinucleotide repeat in the gene coding for theα1A-subunit of the voltage dependent calcium channel. Theaim was to further characterise the SCA6 phenotype METHODS—The SCA6 mutation was investigated in 69 German families with ADCA and 61 patients with idiopathic sporadiccerebellar ataxia and the CAG repeat length of the expanded allele wascorrelated with the disease phenotype. RESULTS—Expanded alleles were found in nine of 69 families as well as in four patients with sporadic disease. Diseaseonset ranged from 30 to 71 years of age and was significantlylater than in other forms of ADCA. Age at onset correlated inverselywith repeat length. The SCA6 phenotype comprises predominantlycerebellar signs in concordance with isolated cerebellar atrophy onMRI. Non-cerebellar systems were only mildly affected with external ophthalmoplegia, spasticity, peripheral neuropathy, and parkinsonism. Neither these clinical signs nor progression rate correlated with CAGrepeat length. CONCLUSIONS—This study provides the first detailedcharacterisation of the SCA6 phenotype. Clinical features apart fromcerebellar signs were highly variable in patients with SCA6. Bycomparison with SCA1, SCA2, and SCA3 no clinical orelectrophysiological finding was specific for SCA6. Therefore, themolecular defect cannot be predicted from clinical investigations. InGermany, SCA6 accounts for about 13% of families with ADCA. However,up to 30% of SCA6 kindreds may be misdiagnosed clinically as sporadicdisease due to late manifestation in apparently healthy parents.Genetic testing is therefore recommended for the SCA6 mutation also inpatients with putative sporadic ataxia. |
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