Endophenotypical drift in Huntington’s disease: a 5-year follow-up study

Orphanet Journal of Rare Diseases

Ida U. Larsen¹  Esben Budtz-Jørgensen²  Marie N. N. Hellem³  Troels T. Nielsen³  Lena E. Hjermind³  Jørgen E. Nielsen³  Tua Vinther-Jensen⁴  Asmus Vogel⁵  Rebecca K. Hendel⁵ 

[1] Department of Neurology, Bispebjerg-Frederiksberg Hospital, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark;Department of Public Health, Section of Biostatistics, University of Copenhagen, Øster Farimagsgade 5, 1014, Copenhagen, Denmark;The Neurogenetics Clinic, Danish Dementia Research Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark;The Neurogenetics Clinic, Danish Dementia Research Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark;Department of Neurology, Bispebjerg-Frederiksberg Hospital, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark;The Neurogenetics Clinic, Danish Dementia Research Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark;Department of Psychology, University of Copenhagen, Øster Farimagsgade 2, 1014, Copenhagen, Denmark;

关键词: Huntington’s disease;    Endophenotype;    Psychiatric symptoms;    Cognitive symptoms;   

DOI  :  10.1186/s13023-021-01967-2

来源: Springer

【 摘 要 】

BackgroundHuntington’s disease (HD) is clinically characterized by progressing motor, cognitive and psychiatric symptoms presenting as varying phenotypes within these three major symptom domains. The disease is caused by an expanded CAG repeat tract in the huntingtin gene and the pathomechanism leading to these endophenotypes is assumed to be neurodegenerative. In 2012/2013 we recruited 107 HD gene expansion carriers (HDGECs) and examined the frequency of the three cardinal symptoms and in 2017/2018 we followed up 74 HDGECs from the same cohort to describe the symptom trajectories and individual drift between the endophenotypes as well as potential predictors of progression and remission.ResultsWe found higher age to reduce the probability of improving on psychiatric symptoms; increasing disease burden score ((CAG-35.5) * age) to increase the risk of developing cognitive impairment; increasing disease burden score and shorter education to increase the risk of motor onset while lower disease burden score and higher Mini Mental State Examination increased the probability of remaining asymptomatic. We found 23.5% (N = 8) to improve from their psychiatric symptoms.ConclusionsThere is no clear pattern in the development of or drift between endophenotypes. In contrast to motor and cognitive symptoms we find that psychiatric symptoms may resolve and thereby not entirely be caused by neurodegeneration. The probability of improving from psychiatric symptoms is higher in younger age and advocates for a potential importance of early treatment.

【 授权许可】

CC BY