Clinical Information

Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disorder characterized by ataxia, choreoathetosis, dementia, and psychiatric disturbance in adults and ataxia, myoclonus, seizures, and progressive intellectual deterioration in children. Characteristic neuropathologic observations include degeneration of the dentatorubral and pallidoluysian systems of the central nervous system.

The prevalence of DRPLA depends on the geographic and ethnic origin of the population being studied. DRPLA was first described in a European individual without a family history; however, it is predominantly found as an inherited condition and is most prevalent in Japan (0.2-0.7 per 100,000). Although rare, DRPLA has been identified in other populations, including Europe and North America.

DRPLA is caused by an expansion of the CAG trinucleotide repeat in the ATN1 (DRPLA) gene. This trinucleotide repeat is polymorphic in the general population, with the number of repeats ranging from 7 to 35. In affected individuals, the CAG expansion ranges from 48 to 93 repeats. As with other trinucleotide repeat disorders, anticipation is frequently observed, and larger CAG expansions are associated with earlier onset and a more severe and rapid clinical course. In DRPLA, the observed anticipation appears to be significantly greater in paternal transmissions.