Atypical Huntington's disease onset: Clinical and genetic analysis

Huntington's disease (HD) is difficult to diagnose in the early stages. One reason is that the HD clinical manifestations at onset vary widely and sometimes may be atypical. In this review we primarily sought information on HD affected patients who initially presented with movement disorders other than chorea. We also investigated atypical motor presentations in relation to triplet CAG expansions. We identified patients with a final, documented diagnosis of HD and selected 79 patients according to their onset manifestations. CAG repeats were analysed by the published molecular test assay. In 24 HD affected patients who had atypical motor symptoms at onset, we identified four types of initial clinical manifestations: parkinsonism, ataxia, dystonia and tourettisms. All the patients had a CAG repeat expansion (>36) in the IT 15 gene. Our findings suggest that HD affected patients with atypical movement disorders at onset have larger CAG expansions (mean trinucleotide repeat expansion: 53 CAGs) and an earlier age at onset (mean: 28 years) than HD patients with typical onset chorea and severe psychiatric manifestations (p