Late-onset Huntington’s disease with 40–42 CAG expansion

INTRODUCTION: Huntington’s disease (HD) is a rare autosomal dominant neurodegenerative disorder caused by a CAG expansion greater than 35 in the IT-15 gene. There is an inverse correlation between the number of pathological CAG and the age of onset. However, CAG repeats between 40 and 42 showed a wider onset variation. We aimed to investigate potential clinical differences between patients with age at onset ≥ 60 years (late onset-HD) and patients with age at onset between 30 and 59 years (common-onset HD) in a cohort of patients with the same CAG expansions (40–42). METHODS: A retrospective analysis of 66 HD patients with 40–41–42 CAG expansion was performed. Patients were investigated with the Unified Huntington’s Disease Rating Scale (subitems I–II–III and Total Functional Capacity, Functional Assessment and Stage of Disease). Data were analysed using χ(2), Fisher’s test, t test and Pearson’s correlation coefficient. GENMOD analysis and Kaplan-Meier analysis were used to study the disease progression. RESULTS: The age of onset ranged from 39 to 59 years in the CO subgroup, whereas the LO subgroup showed an age of onset from 60 to 73 years. No family history was reported in 31% of the late-onset in comparison with 20% in common-onset HD (p = 0.04). No difference emerged in symptoms of onset, in clinical manifestations and in progression of disease between the two groups. CONCLUSION: There were no clinical differences between CO and LO subgroups with 40–42 CAG expansion. There is a need of further studies on environmental as well genetic variables modifying the age at onset. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10072-019-04177-8) contains supplementary material, which is available to authorized users.