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Comparative Study
. 2020 Apr;41(4):869-876.
doi: 10.1007/s10072-019-04177-8. Epub 2019 Dec 9.

Late-onset Huntington's disease with 40-42 CAG expansion

Elisa Capiluppi  1 , Luca Romano  2 , Paola Rebora  3 , Lorenzo Nanetti  4 , Anna Castaldo  4 , Cinzia Gellera  4 , Caterina Mariotti  4 , Antonella Macerollo  5   6 , M Giuliana Cislaghi  2
Affiliations
Comparative Study

Late-onset Huntington's disease with 40-42 CAG expansion

Elisa Capiluppi et al. Neurol Sci. 2020 Apr.

Abstract

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 χ2, 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.

Keywords: Age of onset; Epidemiology; Huntington’s disease.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
a The box-plot analysis showed a negative correlation between CAG repeat size and age at onset in HD patients (p = 0.0403), although the sample had previously been selected for CAG expansion range between 40 and 42. b Kaplan-Meier analysis showed the effect of age at onset on progression time to the severe stage assessed by the Total Functional Capacity Scale (log-rak test = 0.0351, p = 0.851). There was no difference in the prognosis between the two groups. c Mean behavioural score for the two groups at baseline and follow-up. P value refers to the difference among the two groups on the change in the behavioural score during follow-up by the linear model
See this image and copyright information in PMC

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