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

OBJECTIVES: 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. SETTING: 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. PARTICIPANTS: 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. PRIMARY AND SECONDARY OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: 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.

The Prevalence of Huntington's Disease.

BACKGROUND: Reviews of the epidemiology of Huntington's disease (HD) suggest that its worldwide prevalence varies widely. This review was undertaken to confirm these observations, to assess the extent to which differences in case-ascertainment and/or diagnosis might be responsible, and to investigate whether the prevalence pattern has changed over the past 50 years. METHODS: Eighty two relevant studies were identified from Medline and Embase, previous reviews, scrutiny of references from included and excluded studies and enquiry among those interested in the field. RESULTS: 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. There was evidence of an increasing prevalence of between 15 and 20% per decade in studies from Australia, North America and Western Europe. CONCLUSIONS: The prevalence of HD varies more than tenfold between different geographical regions. This variation can in part be attributed to differences in case-ascertainment and/or diagnostic criteria, but there is consistent evidence of a lower incidence in Asian populations. There is also evidence that in Australia, North America and in Western Europe (including the United Kingdom), prevalence has increased over the past 50 plus years.

Huntington disease: natural history, biomarkers and prospects for therapeutics.

Huntington disease (HD) can be seen as a model neurodegenerative disorder, in that it is caused by a single genetic mutation and is amenable to predictive genetic testing, with estimation of years to predicted onset, enabling the entire range of disease natural history to be studied. Structural neuroimaging biomarkers show that progressive regional brain atrophy begins many years before the emergence of diagnosable signs and symptoms of HD, and continues steadily during the symptomatic or 'manifest' period. The continued development of functional, neurochemical and other biomarkers raises hopes that these biomarkers might be useful for future trials of disease-modifying therapeutics to delay the onset and slow the progression of HD. Such advances could herald a new era of personalized preventive therapeutics. We describe the natural history of HD, including the timing of emergence of motor, cognitive and emotional impairments, and the techniques that are used to assess these features. Building on this information, we review recent progress in the development of biomarkers for HD, and potential future roles of these biomarkers in clinical trials.

Huntington's Disease - A Brief Historical Perspective.

Although the disease today known as Huntington's was described as early as the mid-19th century, knowledgeable physicians despaired of finding successful therapies and affected families largely kept it hidden. Starting in the late 1960 s, the confluence of grass-roots advocacy by HD family members, advances in Parkinson's treatment, and the development of molecular genetics and neuroscience helped turn HD into a focus of growing biomedical research. While therapies lag behind laboratory discoveries, disease altering interventions are now moving closer to the clinic. The Journal of Huntington's Disease is a welcome new resource in this effort.

Chorea and community in a nineteenth-century town.

The dominant historical narrative of Huntington's disease (Huntington's chorea) has portrayed the early American sufferers from this disorder as marginalized and vilified. This article argues, however, that afflicted families in East Hampton, New York--the site of George Huntington's mid-nineteenth-century observations--were mostly accepted and integrated within the community, some of them as members of the gentry and active participants in local governance. As descendants of early English settlers in this multiracial town, these white Presbyterian families, some of whose members were afflicted with what was locally called "St. Vitus's dance" or "that disorder," were always defined as "one of ours." While this fatal inherited neurological illness became more secret and hidden toward the end of the nineteenth century, this article suggests that it was larger cultural and social changes, rather than factors intrinsic to the disease, that led to the shift. The East Hampton story suggests the ways in which specific historical circumstances in a community may shape the-social meanings of even so severe a disease as Huntington's, and that social integration of the afflicted families may have helped mitigate the suffering of the disease.