Dentatorubral pallidoluysian atrophy (DRPLA) is an autosomal dominantly inherited neurodegenerative disorder with symptoms of progressive cerebellar ataxia, myoclonic epilepsy, choreoathetosis and dementia. The age of onset is variable, with first symptoms usually manifesting in early adulthood. DRPLA is less common in Western countries than, for example, in Japan.
It is caused by a CAG repeat expansion in the atrophin-1 gene ATN1. As in other CAG triplet repeat diseases, anticipation is observed meaning there is an earlier age of disease onset in successive generations with increasing repeat length. Increasing repeat length, especially when inherited from the father, indicates instability in the male germline. In predictive diagnostics, healthy individuals considered at-risk are examined. These are usually first degree relatives of affected individuals. Based on the recommendations of the professional societies, psychotherapeutic care should be provided before, during and after the examination phase.
References
Carroll et al. 2018 Tremor Other Hyperkinet Mov (NY) 8:577 / Yamada 2010, Neuropathology 30:453 / Yamada et al. 2006, Neuropathology 26:346 / Wood et al. 2000, J Cell Biol 150:938 / Komure et al. 1995, Neurology 45:143 / Nagafuchi et al. 1994, Nat Genet 6:14 / Naito et al. 1982, Neurology 32:798