Incidence of adult Huntington's disease in the UK: a UK-based primary care study and a systematic review

Nancy S Wexler, Laura Collett, Alice R Wexler, Michael D Rawlins, Sarah J Tabrizi, Ian Douglas, Liam Smeeth, Stephen J Evans

The prevalence of Huntington's disease (HD) recorded in the UK primary care records has increased twofold between 1990 and 2010. This investigation was undertaken to assess whether this might be due to an increased incidence. We have also undertaken a systematic review of published estimates of the incidence of HD. Incident patients with a new diagnosis of HD were identified from the primary care records of the Clinical Practice Research Datalink (CPRD). The systematic review included all published estimates of the incidence of HD in defined populations. A total of 393 incident cases of HD were identified from the CPRD database between 1990 and 2010 from a total population of 9 282 126 persons. The incidence of HD per million person-years was estimated. From the systematic review, the extent of heterogeneity of published estimates of the incidence of HD was examined using the I(2) statistic. The data showed that the incidence of HD has remained constant between 1990 and 2010 with an overall rate of 7.2 (95% CI 6.5 to 7.9) per million person-years. The systematic review identified 14 independent estimates of incidence with substantial heterogeneity and consistently lower rates reported in studies from East Asia compared with those from Australia, North America and some-though not all-those from Europe. Differences in incidence estimates did not appear to be explained solely by differences in case ascertainment or diagnostic methods. The rise in the prevalence of diagnosed HD in the UK, between 1990 and 2010, cannot be attributed to an increase in incidence. Globally, estimates of the incidence of HD show evidence of substantial heterogeneity with consistently lower rates in East Asia and parts of Europe. Modifiers may play an important role in determining the vulnerability of different populations to expansions of the HD allele.