The Impact of Family History on the Clinical Features of Huntington’s Disease

Kringlen, Gabe; Kinsley, Lisa; Aufox, Sharon; Rouleau, Gerald W.; Bega, Danny

doi:10.3233/jhd-170256

Cited by 8 publications

(8 citation statements)

References 15 publications

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“…Conspicuously, 38.5% of genotype-negative participants suffered from depression and more than 34% suffered from irritability in their lifetimes as the two most frequent psychiatric symptoms, which seems highly frequent. These findings are congruent with depression as the most common symptom, analyzed in validations of the HADS, within normal-population cohorts [53,54], very common late-life depression [55], and especially the impact of a positive HD family history in investigated genotype negative controls within our study [56]. To investigate these effects in more detail, further information about the genotype-negative cohort would have been useful, e.g., how many in the cohort were aware of the negative genotype and how many were still "at risk", without knowing their own molecular-genetic results.…”

Section: Discussionsupporting

confidence: 89%

Another Perspective on Huntington’s Disease: Disease Burden in Family Members and Pre-Manifest HD When Compared to Genotype-Negative Participants from ENROLL-HD

Achenbach

Saft

2021

Brain Sciences

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Background: In addition to the effects on patients suffering from motor-manifest Huntington’s disease (HD), this fatal disease is devasting to people who are at risk, premanifest mutation-carriers, and especially to whole families. There is a huge burden on people in the environment of affected HD patients, and a need for further research to identify at-risk caregivers. The aim of our research was to investigate a large cohort of family members, in comparison with genotype negative and premanifest HD in order to evaluate particular cohorts more closely. Methods: We used the ENROLL-HD global registry study to compare motoric, cognitive, functional, and psychiatric manifestation in family members, premanifest HD, and genotype negative participant as controls. Cross-sectional data were analyzed using ANCOVA-analyses in IBM SPSS Statistics V.28. Results: Of N = 21,116 participants from the global registry study, n = 5174 participants had a premanifest motor-phenotype, n = 2358 were identified as family controls, and n = 2640 with a negative HD genotype. Analysis of variance revealed more motoric, cognitive, and psychiatric impairments in premanifest HD (all p < 0.001). Self-reported psychiatric assessments revealed a significantly higher score for depression in family controls (p < 0.001) when compared to genotype negative (p < 0.001) and premanifest HD patients (p < 0.05). Family controls had significantly less cognitive capacities within the cognitive test battery when compared to genotype negative participants. Conclusions: Within the largest cohort of HD patients and families, several impairments of motoric, functional, cognitive, and psychiatric components can be confirmed in a large cohort of premanifest HD, potentially due to prodromal HD pathology. HD family controls suffered from higher self-reported depression and less cognitive capacities, which were potentially due to loaded or stressful situations. This research aims to sensitize investigators to be aware of caregiver burdens caused by HD and encourage support with socio-medical care and targeted psychological interventions. In particular, further surveys and variables are necessary in order to implement them within the database so as to identify at-risk caregivers.

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Section: Discussionsupporting

confidence: 89%

Another Perspective on Huntington’s Disease: Disease Burden in Family Members and Pre-Manifest HD When Compared to Genotype-Negative Participants from ENROLL-HD

Achenbach

Saft

2021

Brain Sciences

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“…Additionally, given their young age of onset and the genetic nature of HD, these participants are more likely to be caretakers for living family members affected by HD, which has been shown to cause high rates of family dysfunction, psychological stress, and significantly affect quality of life [27][28][29]. Even when controlling for CAG repeat length, HD patients with a family history of HD have been shown to have earlier depression onset and are more likely to have behavioral manifestations as their initial major symptom compared to de novo HD patients [30]. Thus, the young age of onset group may have to deal with the emotional stress of their HD, which is potentially compounded by the emotional stress of caring for ailing HD family members [31].…”

Section: Discussionmentioning

confidence: 99%

Influence of Age of Onset on Huntington’s Disease Phenotype

Kwa¹,

Larson

Chen

et al. 2020

Tremor and Other Hyperkinetic Movements

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Background: Older patients with Huntington's disease (HD) are often thought to have a slower progressing disease course with less behavioral symptoms than younger patients. However, phenotypic differences based on age of onset have not been well characterized in a large HD population. This study will determine the difference in manifestations and disease progression between patients with young, typical, and late onset adult HD at different stages of disease. Methods: Data obtained from Enroll-HD. Adults with manifest HD were included. Age groups were defined as young onset (YO: 20-29 years), typical onset (TO: 30-59 years), and late onset (LO: 60+ years). Subjects were categorized by TFC score, from Stage I (least severe) to Stage V (most severe). Motor, cognitive, and behavioral symptoms were analyzed. Descriptive statistics and Bonferroni p-value correction for pairwise comparison were calculated. Results: 7,311 manifest HD participants were included (612 YO, 5,776 TO, and 923 LO). The average decline in TFC score from baseline to second visit (1.5-2.5 years) was significantly faster for YO (-1.75 points) compared to TO (-1.23 points, p = 0.0105) or LO (-0.97 points, p = 0.0017). Motor deficits were worse for LO participants at early stages of HD, and worse for YO participants at advanced stages. YO and TO participants had greater burden of behavioral symptoms at early stages of disease compared to LO. Discussion: YO is predictive of a faster functional decline for adults with HD when compared to those with TO and LO. Motor and behavioral manifestations differ based on age of onset. Highlights: This study compares HD manifestations while controlling for disease severity, detailing robust phenotypic differences by age of onset alone. These findings have implications for the clinical management of HD symptoms and have the possibility to improve prognostic and treatment precision.

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“…Individuals with a positive family history of HD are more likely to report behavioral manifestations as the major initial symptom of HD. 39 Individuals with earlier onset HD are more likely to have an affected family member and may be more aware of their HD risk and more attuned to recognizing subtler symptoms at an earlier age. Significantly, fewer late onset individuals had a family history of HD in a large observational study.…”

Section: Discussionmentioning

confidence: 99%

“…Additional confounding factors not accounted for in the analysis, such as, family history of HD, may also need to be explored in the future. Individuals with a positive family history of HD are more likely to report behavioral manifestations as the major initial symptom of HD 39 . Individuals with earlier onset HD are more likely to have an affected family member and may be more aware of their HD risk and more attuned to recognizing subtler symptoms at an earlier age.…”

Section: Discussionmentioning

confidence: 99%

Age of onset and behavioral manifestations in Huntington's disease: An Enroll‐HD cohort analysis

et al. 2020

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Huntington's disease is associated with motor, cognitive and behavioral dysfunction. Behavioral symptoms may present before, after, or simultaneously with clinical disease manifestation. The relationship between age of onset and behavioral symptom presentation and severity was explored using the Enroll-HD database. Manifest individuals (n = 4469) were initially divided into three groups for preliminary analysis:

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The Impact of Family History on the Clinical Features of Huntington’s Disease

Abstract: A positive family history of HD appears to be associated with an earlier onset of depression and overall disease manifestations. Implications regarding the role of genetic versus environmental contributions to symptom onset in HD are discussed.

Cited by 8 publications

References 15 publications

Another Perspective on Huntington’s Disease: Disease Burden in Family Members and Pre-Manifest HD When Compared to Genotype-Negative Participants from ENROLL-HD

Another Perspective on Huntington’s Disease: Disease Burden in Family Members and Pre-Manifest HD When Compared to Genotype-Negative Participants from ENROLL-HD

Influence of Age of Onset on Huntington’s Disease Phenotype

Age of onset and behavioral manifestations in Huntington's disease: An Enroll‐HD cohort analysis

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