Description

Scientific Background

DRPLA is an autosomal dominantly inherited neurodegenerative disorder with leading symptoms of progressive cerebellar ataxia, myoclonus epilepsy, choreoathetosis and dementia. The age of onset is variable, usually with first symptoms 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 an earlier age of onset of disease 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 at-risk individuals are examined. These are usually first-degree relatives of affected individuals. According to the German Genetic Diagnostics Act (GenDG), genetic counseling should be offered with every diagnostic genetic examination. In case of predictive genetic diagnostics, genetic counseling must be offered before the examination and after the results are available. 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. 2018; 8. doi:10.7916/D81N9HST / Yamada M 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