Long-term disability and prognosis in dentatorubral-pallidoluysian atrophy: a correlation with CAG repeat length.

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Dentatorubral-pallidoluysian atrophy (DRPLA ) is a rare autosomal dominant neurodegenerative disorder caused by CAG repeat expansion . Previous studies demonstrated that the onset of DRPLA is closely associated with CAG repeat length . However , the natural history of DRPLA has not yet been evaluated . We here retrospectively investigated the factors that determine the disease milestones and prognosis in 183 Japanese patients genetically diagnosed with DRPLA . We determined the age at onset , age at which each of the subsequent clinical manifestations appeared , age at becoming wheelchair-bound , and age at death . Kaplan-Meier analysis revealed that the patients with CAG repeats larger than the median length of 65 repeats developed each of the clinical features of DRPLA at a younger age than those with <65 repeats . The patients became wheelchair-bound at a median age of 33 years (n = 61 ; range , 3 -77 years ) and died at a median age of 49 years (n = 23 ; range , 18 -80 years ). The ages at becoming wheelchair-bound and at death strongly correlated with the expanded CAG repeat length . Moreover , the patients with >or =65 CAG repeats showed a more severe long -term disability and a poorer prognosis . In contrast , the rate of progression after the onset did not correlate with CAG repeat length . The CAG repeat length may have a considerable effect on not only the disease onset but also the disease milestones and prognosis in DRPLA patients . These effects of CAG repeat length may be relevant in designing future clinical therapeutic trials .