Huntington disease (HD) is most prevalent among populations of western European descent and isolated populations where founder effects may operate. The aim of this study was to examine the epidemiology of HD in Cyprus, an island in southern Europe with extensive western European colonization in the past. All registered HD patients in the Cyprus, since 1994, were included. Detailed pedigrees and clinical information were recorded and maps, showing the geographic distribution of HD, were constructed. Requests for genetic testing were also examined. The project identified 58 clinically manifested cases of HD belonging to 19 families. The 16 families of Cypriot origin were concentrated in a confined geographical cluster in southeast Cyprus. In 2015, prevalence of symptomatic HD was 4.64/100 000 population, while incidence was 0.12/100 000 person-years. Prevalence displayed a marked increase during the past 20 years. Disease characteristics of HD patients were similar to those reported in western European populations. Lastly, the uptake of predictive and/or prenatal testing was limited. HD disease characteristics, incidence and prevalence in Cyprus were comparable to western European populations. Together with the geographical clustering observed, these results support the possibility for a relatively recent founder effect of HD in Cyprus, potentially of western European origin.
Background and aimHuntington’s disease (HD) is a fully penetrant, mainly adult-onset, autosomal dominant disorder. HD is caused by repetitions of the triplet CAG in chr 4 (4p16.3), which are pathogenic if ≥36. Globally, the prevalence is highest among populations of western European descent. In more isolated populations the origin of HD is usually a result of founder effects, which can give rise to higher than normal prevalence as well as geographical clustering. Our aim was to conduct a detailed epidemiological investigation of HD in the island of Cyprus.MethodsAll registered Greek Cypriot HD patients were analysed from 1984 onwards. Detailed pedigrees and maps, examining the geographic distribution of the disorder, were constructed.ResultsEighty confirmed cases of HD were identified since 1984 belonging to 16 independent families concentrated in a small cluster spanning the Famagusta and Larnaca districts. Three cases were juvenile HD (JHD). In 2015 the prevalence was 7.61/100,000, and the incidence 0.12/100.000. The crude average annual incidence from 1984 to 2015 was 0.26/100000 (95% CI: 0.20–0.34). The 5-, 10-, and 15-year survival probability was 85.2%, 63.0% and 40.7% respectively, with average disease duration of 12.2 years, excluding JHD. The average age at onset was 44.2 years and the average number of CAG repeats in the mutant allele was 44. Paternal inheritance had in general a more adverse disease profile. The age at onset was found to decrease significantly over decades and with increasing number of CAG repeats.ConclusionsCyprus has HD prevalence and incidence higher than other southern European countries, making the possibility for a founder effect very likely. The geographical clustering observed points to a very likely western European origin of the disease, given the strong presence of such populations in the affected region during the middle-ages. Disease characteristics such as the median number of CAG repeats, age at onset and disease duration are comparable to other countries.
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