Dentatorubral-Pallidoluysian Atrophy: An Update
Aim: Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare, autosomal dominantly inherited disorder characterised by myoclonus, epilepsy, ataxia and dementia. Diagnosis is challenging due to the heterogeneous presentation and symptomatic overlap with other spinocerebellar ataxias. Symptoms vary according to age of onset, with a mean age-at-onset at 31. A CAG repeat expansion in the gene ATN1 results in neuronal intranuclear inclusions, variable neuronal loss and astrocytosis in the globus pallidus, dentate and red nuclei. No disease-modifying or curative treatments are currently available
Methods: We performed an online literature search using PubMed for all articles published on the topics of DRPLA or ATN1 over the last 10-years in an English Language format. Where these articles cited other research as support for findings, or statements, these articles were also reviewed. Contemporary articles from related research fields (e.g. Huntington's Disease) were also included to support statements.
Results: Forty-seven articles were identified, 10 were unobtainable and 10 provided no relevant information. The remaining 27 articles were then used for the review template: 7 case reports, 7 case series, 6 model system articles (1 review article), 4 population clinical and genetic studies (1 review article), 2 general review articles and 1 human gene expression study. Other cited articles or research from related fields gave a further 42 articles, producing a total of 69 articles cited: 15 case series (including 8 family studies), 14 model systems (1 review article), 14 population clinical and genetic studies (2 review articles), 10 case reports, 8 clinical trials/guidelines, 4 genetic methodology articles, 3 general review articles and 1 human gene expression study.
Discussion: DRPLA remains an intractable, progressive, neurodegenerative disorder without effective treatment. Early recognition of the disorder may improve patient understanding, and access to services and treatments. Large-scale studies are lacking, but required to characterise the full allelic architecture of the disorder in all populations, and the heterogeneous phenotypic spectrum including neuroimaging findings, possible biomarkers and responses to treatment.