Clinical and genetic characteristics of late-onset Huntington's disease

Oosterloo, Mayke; Bijlsma, Emilia K.; Kuijk, Sander M. J. van; Minkels, Floor N. E.; Die-Smulders, Christine E. de

doi:10.1016/j.parkreldis.2018.11.009

Cited by 22 publications

(47 citation statements)

References 21 publications

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“…The ratio of juvenile onset cases (3.3%) was slightly lower than the 5% described in other studies (9,14). All of these patients had a repeat length above 50 and a positive family history where the affected parent was the father.…”

Section: Discussioncontrasting

confidence: 58%

“…One patient with juvenile onset presented with the atypical Westphal phenotype (13). 7 patient of late disease onset was identi ed, representing 7.8% of all cases, which is well within the range (4.4-25%) reported previously (9,14). Each of these patients had a repeat length below 46, and evidence of an affected parent was present in only 2 out of 7 cases.…”

Section: Discussionmentioning

confidence: 53%

“…Some of these patients present atypical symptoms like rigidity, brady-hypokinesis, postural instability and dysarthria, a phenotype referred to as the Westphal-variant (13). The frequency of late-onset HD varies widely in different studies with a range between 4.4-25% (9,14). In these cases, the course of the disease tends to be mild, and repeat lengths are usually below 50 (9,14).…”

Section: Introductionmentioning

confidence: 99%

“…The frequency of late-onset HD varies widely in different studies with a range between 4.4-25% (9,14). In these cases, the course of the disease tends to be mild, and repeat lengths are usually below 50 (9,14). Regarding disease course, HD is a progressive condition resulting in death within 10-20 years (11), the juvenile onset being associated with shorter and the late onset with longer disease duration (3,12).…”

Section: Introductionmentioning

confidence: 99%

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Epidemiologic characteristics of a Hungarian subpopulation of Huntington’s Disease patients

Despotov

Zádori

Veres

et al. 2020

Preprint

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Background: recent advances in the therapeutic options may prevent deterioration related to Huntington’s disease (HD) even at the presymptomatic stage. However, a well-characterized patient population is essential for screening and outcome monitoring as well. Accordingly, the aim of this study was to describe the characteristics of a Hungarian subpopulation of HD patients and mutation carriers diagnosed at the University of Szeged.Methods: we conducted a search for International Classification of Diseases (ICD) code G10H0 in the local medical database for the period between 1 January 1998 and 31 December 2018.Results: we identified 90 HD cases (male: 45, female: 45) and 34 asymptomatic carriers (male: 15, female: 19). The median age of onset was 45 years (range: 16-79). There were 3 cases of juvenile (3.3%), and 7 of late disease onset (7.8%). The median repeat length was 43 (range: 36-70) for the pathological and 19 for the non-pathological alleles (range: 9-35). 17.5% of the pathological alleles was in the decreased penetrance range, while 7% of non-pathological alleles was intermediate.Conclusions: the genetic and clinical features of the population examined in present study was in line with the previous Hungarian study as well as with international literature, the exceptions being the higher ratio of reduced penetrance and intermediate alleles.

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Section: Discussioncontrasting

confidence: 58%

Section: Discussionmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Epidemiologic characteristics of a Hungarian subpopulation of Huntington’s Disease patients

Despotov

Zádori

Veres

et al. 2020

Preprint

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“…This subgroup, named late-onset HD (LO-HD), was defined with an onset after 49 years [7,9,18] or in more recent studies after 59 years [4,11,12,15]. LO-HD accounts between 4.4 and 25% in small cohorts [4,7,9,11,12,15,18] and 11.4% in a larger cohort [20]. LO-HD patients have frequently negative family history; consequentially, the diagnosis might be more difficult and the prevalence results underestimated.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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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 (commononset 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.

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Application Value of Serum Neurofilament Light Protein for Disease Staging in Huntington's Disease

Bao

Xie

et al. 2023

Movement Disorders

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Background Neurofilament light protein (NfL) has been proven to be a sensitive biomarker for Huntington's disease (HD). However, these studies did not include HD patients at advanced stages or with larger CAG repeats (>50), leading to a knowledge gap of the characteristics of NfL. Methods Serum NfL (sNfL) levels were quantified using an ultrasensitive immunoassay. Participants were assessed by clinical scales and 7.0 T magnetic resonance imaging. Longitudinal samples and clinical data were obtained. Results Baseline samples were available from 110 controls, 90 premanifest HD (pre‐HD) and 137 HD individuals. We found levels of sNfL significantly increased in HD compared to pre‐HD and controls (both P < 0.0001). The increase rates of sNfL were differed by CAG repeat lengths. However, there was no difference in sNfL levels in manifest HD from early to late stages. In addition, sNfL levels were associated with cognitive measures in pre‐HD and manifest HD group, respectively. The increased levels of sNfL were also closely related to microstructural changes in white matter. In the longitudinal analysis, baseline sNfL did not correlate with subsequent clinical function decline. Random forest analysis revealed that sNfL had good power for predicting disease onset. Conclusions Although sNfL levels are independent of disease stages in manifest HD, it is still an optimal indicator for predicting disease onset and has potential use as a surrogate biomarker of treatment effect in clinical trials. © 2023 International Parkinson and Movement Disorder Society.

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Clinical and genetic characteristics of late-onset Huntington's disease

Cited by 22 publications

References 21 publications

Epidemiologic characteristics of a Hungarian subpopulation of Huntington’s Disease patients

Epidemiologic characteristics of a Hungarian subpopulation of Huntington’s Disease patients

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

Application Value of Serum Neurofilament Light Protein for Disease Staging in Huntington's Disease

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