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Clinical and genetic characteristics of late-onset Huntington's disease
Mayke Oosterloo1, Emilia K Bijlsma2, Sander Mj van Kuijk3
1Department of Neurology, Maastricht University Medical Center, Maastricht, the Netherlands; Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
Insights
Late-onset Huntington's disease presents with more gait and balance issues as initial symptoms. Contrary to assumptions, its clinical course is not milder than common-onset HD, posing diagnostic challenges due to infrequent family history.
Area of Science:
- Neurology
- Genetics
- Clinical Medicine
Background:
- Late-onset Huntington's disease (LO-HD), defined as onset after 59 years, is often presumed to have a milder clinical course.
- Existing literature on LO-HD is limited and provides inconclusive findings regarding its characteristics and progression.
Purpose of the Study:
- To investigate and compare the clinical features of late-onset Huntington's disease (LO-HD) with common-onset HD.
- To analyze differences in initial symptoms, disease progression, genetic factors, and family history between LO-HD and common-onset HD cohorts.
Main Methods:
- A comparative analysis was conducted on a large cohort of Huntington's disease (HD) patients from a registry database.
- Participants were categorized into late-onset (>59 years) and common-onset (30-50 years) groups.
- Exclusion criteria included missing or ≤35 CAG repeat size, and UHDRS motor score ≤5. Clinical symptoms, disease progression, CAG repeat size, and family history were compared.
Main Results:
- Late-onset HD (11.4% of cohort) more frequently presented with gait and balance problems as the first symptom compared to common-onset HD.
- While overall motor and cognitive performance were worse in late-onset HD, motor progression was slower.
- Late-onset HD patients exhibited lower CAG repeat sizes and a significantly lower rate of positive family history.
Conclusions:
- Late-onset HD patients frequently experience gait and balance issues as initial symptoms, and their disease progression is not milder than common-onset HD, except for slower motor progression.
- The higher incidence of negative family history in late-onset HD may complicate diagnosis.
- Gait and balance problems could serve as key indicators for diagnosing HD in elderly individuals.
Background:
The frequency of late-onset Huntington's disease (>59 years) is assumed to be low and the clinical course milder. However, previous literature on late-onset disease is scarce and inconclusive.
Objective:
Our aim is to study clinical characteristics of late-onset compared to common-onset HD patients in a large cohort of HD patients from the Registry database.
Methods:
Participants with late- and common-onset (30-50 years)were compared for first clinical symptoms, disease progression, CAG repeat size and family history. Participants with a missing CAG repeat size, a repeat size of ≤35 or a UHDRS motor score of ≤5 were excluded.
Results:
Of 6007 eligible participants, 687 had late-onset (11.4%) and 3216 (53.5%) common-onset HD. Late-onset (n = 577) had significantly more gait and balance problems as first symptom compared to common-onset (n = 2408) (P < .001). Overall motor and cognitive performance (P < .001) were worse, however only disease motor progression was slower (coefficient, -0.58; SE 0.16; P < .001) compared to the common-onset group. Repeat size was significantly lower in the late-onset (n = 40.8; SD 1.6) compared to common-onset (n = 44.4; SD 2.8) (P < .001). Fewer late-onset patients (n = 451) had a positive family history compared to common-onset (n = 2940) (P < .001).
Conclusions:
Late-onset patients present more frequently with gait and balance problems as first symptom, and disease progression is not milder compared to common-onset HD patients apart from motor progression. The family history is likely to be negative, which might make diagnosing HD more difficult in this population. However, the balance and gait problems might be helpful in diagnosing HD in elderly patients.