How Many People Have a Huntington's Disease Expansion: A Population-Based Prevalence Study in Northern Scotland.

Introduction: Previous work demonstrated a prevalence of 14.6 per 100,000 manifest Huntington's disease (HD) patients and 8.3 per 100,000 identified pre-symptomatic gene expansion carriers (IPGEC) in Northern Scotland. Many of those at high risk of having a huntingtin (HTT) gene expansion remain untested with the exact number being unknown.

Objectives: The objective of this study was to estimate how many people in Northern Scotland are at 50% risk of having a HTT gene expansion to help with HD clinic service planning and to calculate how many people could access an effective treatment if available.

Methods: Clinical and pedigree records from the North of Scotland Genetic Clinic were examined to estimate numbers of manifest HD patients, IPGEC, and individuals at 50% risk.

Results: The prevalence of those at 50% risk living in Northern Scotland was 45.2 per 100,000 people. Every manifest HD patient in Northern Scotland has 4.4 relatives at 50% risk and every patient with a HTT gene expansion has 2.9 relatives at 50% risk. There are up to 415 (46.2 per 100,000) adults who could access an effective treatment if available, but this number is likely to be an underestimate as not all manifesting individuals seek diagnosis.

Conclusions: Despite high predictive testing rates, at least 2.2 adults are living with the HTT gene expansion for every one of the 14.5 per 100,000 manifest HD patients in Northern Scotland. Regional variation in rates and ascertainment need to be factored into future service planning, including genetic counselling and testing, management, and treatment delivery.