HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS REGISTER		Author Keyword(s) Vol Page [Advanced]

This Article Full Text Full Text (PDF) web only appendix All Versions of this Article: jnnp.2007.128074v1 79/7/804    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this link to a friend Similar articles in this journal Similar articles in PubMed Add article to my folders Download to citation manager Request Permissions Google Scholar Articles by Wardle, M Articles by Robertson, N P PubMed PubMed Citation Articles by Wardle, M Articles by Robertson, N P

Dentatorubral pallidoluysian atrophy in South Wales

¹ Department of Neurology, Ophthalmology and Audiological Medicine, Cardiff University, Cardiff, UK
² Department of Psychological Medicine, School of Medicine, Cardiff University, Cardiff, UK
³ Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, UK

Correspondence to:
Dr M Wardle, Department of Neurology, Ophthalmology and Audiological Medicine, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK; mark{at}wardle.org

Background: Dentatorubral 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 the dentatorubral and pallidoluysian systems. DRPLA has a marked ethnic predilection, most commonly reported in Japan and thought to be rare in Caucasian populations.

Methods: We describe the clinical and genetic characteristics of 17 patients with DRPLA segregating in four families in South Wales.

Results: There was marked clinical heterogeneity with considerable overlap of symptoms and signs between and within families. The age of onset ranged from 34 to 60 years with an earlier onset associated with myoclonic epilepsy and a later onset associated with a Huntington disease-like presentation. We 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 polymorphisms in 306 Welsh control patients identified 14 (4.6%) with repeat lengths in the high-normal range, compared with 0% and 7.4% in previously reported north American Caucasian and Japanese control populations, respectively.

Conclusions: DRPLA 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.