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 of the disorder; 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.

Dentatorubral-pallidoluysian atrophy is caused by an expansion of a CAG trinucleotide repeat in the ATN1 gene. This trinucleotide repeat is polymorphic in the general population, with the number of repeats ranging from 6 to 35. Affected individuals, have 48 or greater CAG repeats. Repeat sizes between 35 and 47 are associated with incomplete penetrance and a milder clinical phenotype. 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. More marked expansion may occur with paternal transmission.