BackgroundDentatorubral pallidoluysian atrophy (DRPLA) is a rare, autosomal dominant, clinically heterogeneous neurodegenerative disorder characterised clinically by progressive dementia, ataxia, chorea, myoclonic epilepsy and psychiatric disturbance and pathologically by combined degeneration of dentatorubral and pallidoluysian systems. DRPLA has a marked ethnic predilection, most commonly reported in Japan and thought to be rare in Caucasian populations.
MethodsWe describe the clinical features of 17 patients with DRPLA segregating in four families in South Wales. There was marked clinical heterogeneity with considerable overlap of symptoms and signs between and within families. Age of onset ranged from 34 to 60 years old with an earlier onset associated with myoclonic epilepsy and a later onset associated with a Huntington disease (HD)-like presentation.
ResultsWe identified a distinct haplotype within one family not present within the other three families suggesting that the expansion in at least one family did not arise from an immediate common ancestor. Analysis of repeat length polymorphism in 306 Welsh control patients identified 14 (4.6%) with repeat lengths in the high-normal range, compared to 0% and 7.4% in previously reported North American Caucasian and Japanese control populations.
ConclusionDRPLA may not be as geographically or ethnically restricted as previously thought and the diagnosis should be considered in non-Asian patients presenting with a wide spectrum of neurological disease especially if there is a dominant family history of dementia or movement disorder. The prevalence of high normal length alleles may account for the relatively high prevalence of DRPLA in Wales.
- CAG repeat
- Dentatorubral pallidoluysian atrophy
- Myoclonic epilepsy
- Spinocerebellar ataxia