Gabe Kringlen1,2, Lisa Kinsley1,3, Sharon Aufox1,4, Gerald Rouleau5, Danny Bega3. 1. Graduate Program in Genetic Counseling, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 2. Department of Medical Genetics, Sanford Health, Fargo, ND, USA. 3. Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 4. Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 5. Biostatistics Collaboration Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Abstract
BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. In most cases the disease is inherited from a parent, although a considerable number of affected persons have no reported family history of the disease. While CAG repeat length is negatively correlated with age of symptom onset, variability exists suggesting that other variables may influence symptom onset. OBJECTIVES: The objective of this study is to determine whether awareness of a family history of HD has an impact on symptom onset and disease manifestations. METHODS: Data were obtained from Enroll-HD to compare subjects with a family history of HD to subjects without on various key clinical outcomes. In addition, multiple regressions were performed to investigate the impact of family history on the age at onset of depression and motor symptoms. RESULTS: 4,285 mutation positive subjects were included in the analysis, of which 4.81% had a negative family history. Controlling for CAG repeat length, a positive family history predicted an onset of depression 11.438 years earlier and an onset of motor symptoms 6.681 years earlier when compared to having a negative family history. Subjects with a positive family history were more likely to report behavioral manifestations as the initial major symptom of HD (38.6% vs. 29.6%, p = 0.023), and were more likely to report previous suicidal ideation/attempts (26.2% vs. 20.3%, p = 0.046). CONCLUSIONS: 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.
BACKGROUND:Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. In most cases the disease is inherited from a parent, although a considerable number of affected persons have no reported family history of the disease. While CAG repeat length is negatively correlated with age of symptom onset, variability exists suggesting that other variables may influence symptom onset. OBJECTIVES: The objective of this study is to determine whether awareness of a family history of HD has an impact on symptom onset and disease manifestations. METHODS: Data were obtained from Enroll-HD to compare subjects with a family history of HD to subjects without on various key clinical outcomes. In addition, multiple regressions were performed to investigate the impact of family history on the age at onset of depression and motor symptoms. RESULTS: 4,285 mutation positive subjects were included in the analysis, of which 4.81% had a negative family history. Controlling for CAG repeat length, a positive family history predicted an onset of depression 11.438 years earlier and an onset of motor symptoms 6.681 years earlier when compared to having a negative family history. Subjects with a positive family history were more likely to report behavioral manifestations as the initial major symptom of HD (38.6% vs. 29.6%, p = 0.023), and were more likely to report previous suicidal ideation/attempts (26.2% vs. 20.3%, p = 0.046). CONCLUSIONS: 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.
Entities:
Keywords:
Age at onset; Huntington’s disease; depression; family history; motor symptoms
Authors: Andrew J Aschenbrenner; Bryan D James; Eric McDade; Guoqiao Wang; Yen Ying Lim; Tammie L S Benzinger; Carlos Cruchaga; Alison Goate; Chengjie Xiong; Richard Perrin; Virginia Buckles; Ricardo Allegri; Sarah B Berman; Jasmeer P Chhatwal; Anne Fagan; Martin Farlow; Antoinette O'Connor; Bernardino Ghetti; Neill Graff-Radford; Jill Goldman; Susanne Gräber; Celeste M Karch; Jae-Hong Lee; Johannes Levin; Ralph N Martins; Colin Masters; Hiroshi Mori; James Noble; Stephen Salloway; Peter Schofield; John C Morris; Randall J Bateman; Jason Hassenstab Journal: Alzheimers Dement Date: 2020-01 Impact factor: 21.566