Corresponding Author Michael D. Background: Reviews of the epidemiology of Huntington's disease HD suggest that its worldwide prevalence varies widely. Methods: Eighty two relevant studies were identified from Medline and Embase, reviews, scrutiny of references from included and excluded studies and enquiry among those interested in the field. : The lowest rates were among the Asians and the highest among the Caucasians.
The differences are not fully explained by varying approaches to case-ascertainment or diagnosis. Conclusions: The prevalence of HD varies more than tenfold between different geographical regions. There is also evidence that in Australia, North America and in Western Europe including the United Kingdomprevalence has increased over the past 50 plus years. Huntington's disease HD is a hereditary neurological disorder inherited as an autosomal dominant trait [ 12 ] because of an expanded trinucleotide repeat in a gene on chromosome 4p Although there is an unusually rare juvenile form of the condition [ 4 ], HD usually presents in early middle life with abnormal movements particularly chorea together with psychiatric symptoms including psychosis, depression, and obsessive-compulsive disorder together with progressive cognitive impairment [ 12 ].
Estimates of the prevalence of HD suggest a more than tenfold difference between regions across the world. Three systematic reviews of the prevalence of HD appear to have been published.
Of these, one was confined to sub-Saharan Africa [ 5 ], one only included studies conducted in the United Kingdom [ 6 ] afterand the third [ 7 ] was confined to estimates undertaken between and The review also sought to establish whether the apparent increase in the prevalence of HD, recently reported in the United Kingdom [ 8 ], occurs in other geographical regions. The criteria for inclusion in the systematic review were that studies should have attempted to identify patients with HD among a population of more thanpersons between and June This population exclusion criterion was introduced for 2 reasons.
First, prevalence in smaller populations would provide unreliable estimates.
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Relevant publications including published abstracts were sought from a search of Medline and Embase databases online suppl. Publications were also sought from scrutiny of the references quoted in reviews of the epidemiology of HD [ 91011121314 ] and by examining the reference lists of publications meeting the inclusion criteria. No studies were excluded by virtue of their date, or because of the approach taken to either case ascertainment or the diagnosis of HD. There were no language restrictions.
Relevant details included in publications that met the inclusion criteria were transcribed by MDR and ARW onto specially devised forms. The transcribed data recorded the following:.
The authors' estimate of the prevalence includes confidence intervals wherever provided. In some instances, although studies provided estimates of prevalence, they failed to indicate either the base population size or the of HD patients. In these circumstances, the missing values were determined by back extrapolation.
The heterogeneity of different estimates of prevalence was estimated from the I 2 test [ 15 ]. Relationships between study years, and the prevalence rates for those years, were assessed by Poisson regression analysis and trends were expressed as the percentage increase per decade.
To avoid undue emphasis in favour of studies with estimates of prevalence rates covering more than 1 year, only the rate in the final year was used in the assessment of heterogeneity and in the trend analyses. The removal of duplicate publications, irrelevant reports, and reports among discrete populations yielded 83 studies with population estimates of the prevalence of HD. Further details of the studies in discrete populations are in online supplementary material Annexes 2 and 3. Other excluded studies are shown in online supplementary material Annexes 4 and 5.
The study by Panse [ 17 ], carried out in the Rhineland between andmet the pre-specified inclusion criteria but was excluded on ethical grounds. Friedrich Panse, a German psychiatrist, was deeply involved in the Nazi eugenics program that carried out coercive sterilization and extermination of persons with a wide range of psychiatric and neurological conditions including HD [ 18 ]. We consider that his participation in such a programme compromises his study on both ethical and scientific grounds and urge that future reviews of the epidemiology of HD also consider excluding this publication.
Exclusion of this study left 82 publications for scrutiny and analysis fig. A summary of the geographical distribution of the included studies is shown in table 1. Table 1 Summary of studies of the prevalence of HD. The methods used for case ascertainment and the diagnosis of HD, for each included study, are shown in the online supplementary material Annexes A variety of approaches have been adopted in identifying patients with HD in defined populations.
Some have been based on a scrutiny of the records of hospitals and nursing homes. Others sought information from individual physicians.
In some instances, cases were also identified by enquiry of the families of affected individuals. Case ascertainment in more recent studies was based on the records of medical genetics laboratories.
We were unable, however, to devise a method that would have allowed quantitative analyses of various approaches to case ascertainment for this study. In a majority of studies, the diagnosis of HD was based on clinical features supplemented, in more recent years, by the of genetic analysis. Again, however, we were unable to develop an approach that would have provided a quantitative assessment of the reliability of the diagnostic approaches used in individual studies. Forest plots of prevalence rates by geographical region are shown in figures 2345678.
In all figures, the size of the point estimates of each study reflects their power. Further details of the studies, themselves, can be found in the online supplementary material Annexes Summary of the Poisson regression analyses of prevalence rates by study year expressed in decadesfor each geographical region, are shown in table 2.
This does not, however, include the 3 studies carried out in Africa as the is too few table 2 for reliable conclusions to be drawn. Table 2 Prevalence rate ratios. Figure 2 online suppl. In the forest plot fig.
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The data suggest that in South Africa, the prevalence of HD is similar among Cape coloureds and whites but appears to be substantially less in blacks [ 19 ]. The prevalence among the Bantu population of Zimbabwe [ 20 ] is reported to be greater than that among black South Africans. Figure 3 online suppl. The study by Paradisi et al. The prevalence among black Americans in the United States [ 23 ] 6. Excluding the single study from South America [ 21 ], there was a ificant trend in data from North America table 2between andfor estimates of prevalence to increase with time Figure 4 online suppl.
These range from 0. There was no ificant trend between study years and estimates of prevalence table 2. There was, however, no ificant trend between study dates and prevalence estimates table 2. The 8 included studies from Oceania were all undertaken in Australia between and There is marked heterogeneity fig.
Because of the large of studies undertaken in Western Europe, as a whole, those from the United Kingdom are described separately. As can be seen from figure 7 online suppl. Factors that contribute to the apparent discrepancies between the 2 most recent prevalence estimates for the United Kingdom have been discussed elsewhere [ 8 ]. It is striking that the estimate of prevalence in a study [ 26 ] confined to migrants from the Indian subcontinent 1. Excluding the studies confined to UK migrants from the Indian subcontinent [ 26 ], and those with the juvenile form of HD [ 27 ], there is a ificant trend table 2 of The prevalence rates in the rest of Western Europe are shown in figure 8 online suppl.
There was, overall, a ificant trend table 2 between the study dates and prevalence estimates The studies of HD in discrete populations, shown in the online supplementary material Annex 2, fall into 2 groups. Some [ 303132333435 ] describe clusters of HD families, living in small communities, often with suggestions that affected individuals are those who have descended from a single progenitor. The remaining studies describe estimates of prevalence in populations of less thanThe global population prevalence of HD appears to show a more than tenfold variation across regions.
The very low prevalence rates among blacks in South Africa 0. In North America, Folstein et al.
The similarity between the estimates of prevalence among blacks and whites in North America may be due, at least in part, to mixed race ancestry. The average prevalence rate since - when genetic testing came into routine use - in Asians countries Hong Kong, Japan, South Korea and Taiwan was 0.
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By comparison, the average prevalence rate for the same period, among predominantly Caucasian populations in Australia, Western Europe including the United Kingdom and North America, was 9. Moreover, as discussed earlier, the UK study among UK immigrants from the Indian subcontinent also showed a substantially lower prevalence [ 26 ] than the prevalence that existed in the United Kingdom as a whole. Reduced mutation rates may be responsible for the lower prevalence rates of HD in East Asians.
It has been suggested [ 3637 ] that different haplotypes, between East Asians and Europeans, may be associated with differing mutation rates. Sipila et al. Further research, however, is needed to explain these marked global differences in prevalence. Our study of the prevalence of HD in the United Kingdom [ 7 ] showed that prevalence rates have increased more than twofold between and