The Incidence and Prevalence of Huntington’s Disease: A Systematic Review and Meta-analysis Tamara Pringsheim, MD, MSc, 1 * Katie Wiltshire, MD, 1 Lundy Day, BSc, 1 Jonathan Dykeman, BSc, 1 Thomas Steeves, MD, MSc, 2 Nathalie Jette, MD, MSc 1 1 Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada 2 Department of Medicine, University of Toronto, Toronto, Ontario, Canada ABSTRACT: Huntington’s disease (HD) is a rare, neurodegenerative disorder characterized by chorea, behavioral manifestations, and dementia. The aim of this study was to estimate the incidence and preva- lence of HD through a systematic review of the litera- ture. Medline and Embase databases were searched using terms specific to HD as well as studies of inci- dence, prevalence, and epidemiology. All studies reporting the incidence and/or prevalence of HD were included. Twenty original research articles were included. Eight studies examined incidence, and 17 studies examined prevalence. Meta-analysis of data from four incidence studies revealed an incidence of 0.38 per 100,000 per year (95% confidence interval [CI]: 0.16, 0.94). Lower incidence was reported in the Asian studies (n 5 2), compared to the studies performed in Europe, North America, and Australia (n 5 6). The worldwide service-based prevalence of HD, based on a meta-analysis (n 5 13 studies), was 2.71 per 100,000 (95% CI: 1.55–4.72). Eleven studies were conducted in Europe, North American, and Australia, with an overall prevalence of 5.70 per 100,000 (95% CI: 4.42–7.35). Three studies were conducted in Asia, with an overall prevalence of 0.40 per 100,000 (95% CI: 0.26–0.61). Metaregression revealed a significantly lower preva- lence of HD in Asia, compared to European, North American, and Australian populations. HD is a devastat- ing neurodegenerative disorder with a higher prevalence in Europe, North America, and Australia than in Asia. The difference in prevalence of this genetic disorder can be largely explained by huntingtin gene haplotypes. V C 2012 Movement Disorder Society Key Words: Huntington’s disease; epidemiology; inci- dence; prevalence Huntington’s disease (HD) is a neurodegenerative dis- order characterized by chorea, behavioral and psychiat- ric manifestations as well as dementia. HD is caused by a CAG triplet repeat expansion in the huntingtin gene, which encodes an expanded polyglutamine stretch in the huntingtin protein. This gene is inherited in an autoso- mal dominant manner with age-dependent penetrance. The average CAG tract length in the general population is 16 to 20 repeats. In HD, the CAG tract is expanded to 36 repeats or greater. Intermediate alleles from 27 to 35 repeats do not cause HD, but are potentially unstable during reproduction. The clinical diagnosis of HD is based on the devel- opment of chorea, which is often observed in combi- nation with other movement abnormalities, including dystonia, bradykinesia, and motor incoordination. Be- havioral or psychiatric features, such as personality changes, poor attention, cognitive rigidity, and irrita- bility, are also characteristic, as is dementia. These symptoms, in combination with a family history of the disorder in a pattern of autosomal dominant inheri- tance, are highly suggestive of the diagnosis. Cur- rently, the diagnosis can be formally confirmed by genetic testing. Despite the availability of genetic test- ing, rates of preclinical testing in individuals at risk of HD are extremely low. 1 Because HD is a genetic disorder, prevalence esti- mates may vary considerably, depending on the ------------------------------------------------------------ * Correspondence to: Dr. Tamara Pringsheim, Department of Clinical Neurosciences and Pediatrics, University of Calgary, C4-431, Alberta Children’s Hospital, 2888 Shaganappi Trail NW, Calgary, Alberta, T3B 6A8 Canada; tmprings@ucalgary.ca Funding agencies: This research was supported by the Public Health Agency of Canada. Relevant conflicts of interest/financial disclosures: Nothing to report. Full financial disclosures and author roles may be found in the online version of this article. Received: 1 February 2012; Revised: 20 April 2012; Accepted: 9 May 2012 Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/mds.25075 REVIEW Movement Disorders, Vol. 000, No. 000, 0000 1