Background Huntington disease (HD) frequency is uncertain and epidemiological analyses are requested to determine whether HD prevalence is underestimated. Last epidemiological esteem in Italy was described before HTT gene discovery, reporting a frequency of affected subjects ranging between 2.3 to 4.8/100.000 in Northern Italy.

Aims To determine HD prevalence in Italy.

Methods Since 1997, we started to collect data and DNA samples for diagnosis and research purposes, from HD subjects originating from every part of Italy. To date, we have data and samples from 730 patients from a total of 557 unrelated families. To decrease the bias due to methodological and regional variations, we focused on a well-selected Italian region, Molise, Mid-Southern Italy, showing a population of 313.341 inhabitants at 2013, where Neuromed and LIRH are the only referent Institutions for HD and related diseases.

Results Thirty-four patients had clinical diagnosis of HD, from 31 unrelated families. Twenty-six patients received genetic confirmation, 8 of them had strictly clinical diagnosis. The estimated prevalence was 10.85/100,000 (95% CI: 7.20–14.50). A total of 464 asymptomatic and untested individuals (124 with 50% risk and 156 with 25% risk) were identified on family pedigrees. When including premanifest mutation carriers who had performed a predictive test, we found a total of 42 individuals with an estimated prevalence of 13.40/100.000 (95% CI: 9.35–17.45).

Conclusions Our data suggest, for the first time, that there may be up to 6500 HD patients in Italy and that previous analyses underestimated.