Longitudinal Clinical and Biological Characteristics in Juvenile-Onset Huntington's Disease.
juvenile-onset Huntington disease
longitudinal
neuroimaging
prospective
Journal
Movement disorders : official journal of the Movement Disorder Society
ISSN: 1531-8257
Titre abrégé: Mov Disord
Pays: United States
ID NLM: 8610688
Informations de publication
Date de publication:
01 2023
01 2023
Historique:
revised:
26
08
2022
received:
14
06
2022
accepted:
29
09
2022
pmc-release:
01
01
2024
pubmed:
2
11
2022
medline:
21
1
2023
entrez:
1
11
2022
Statut:
ppublish
Résumé
Juvenile-onset Huntington's disease (JOHD) is a rare form of Huntington's disease (HD) characterized by symptom onset before the age of 21 years. Observational data in this cohort is lacking. Quantify measures of disease progression for use in clinical trials of patients with JOHD. Participants who received a motor diagnosis of HD before the age of 21 were included in the Kids-JOHD study. The comparator group consisted of children and young adults who were at-risk for inheriting the genetic mutation that causes HD, but who were found to have a CAG repeat in the non-expanded range (gene non-expanded [GNE]). Data were obtained between March 17, 2006, and February 13, 2020. There were 26 JOHD participants and 78 GNE participants who were comparable on age (16.03 vs. 14.43, respectively) and sex (53.8% female vs. 57.7% female, respectively). The mean annualized decrease in striatal volume in the JOHD group was -3.99% compared to -0.06% in the GNE (mean difference [MD], -3.93%; 95% confidence intervals [CI], [-4.98 to -2.80], FDR < 0.0001). The mean increase in the Unified Huntington's Disease Rating Scale Total Motor Score per year in the JOHD group was 7.29 points compared to a mean decrease of -0.21 point in the GNE (MD, 7.5; 95% CI, [5.71-9.28], FDR < 0·0001). These findings demonstrate that structural brain imaging and clinical measures in JOHD may be potential biomarkers of disease progression for use in clinical trials. Collaborative efforts are required to validate these results in a larger cohort of patients with JOHD. © 2022 International Parkinson and Movement Disorder Society.
Sections du résumé
BACKGROUND
Juvenile-onset Huntington's disease (JOHD) is a rare form of Huntington's disease (HD) characterized by symptom onset before the age of 21 years. Observational data in this cohort is lacking.
OBJECTIVES
Quantify measures of disease progression for use in clinical trials of patients with JOHD.
METHODS
Participants who received a motor diagnosis of HD before the age of 21 were included in the Kids-JOHD study. The comparator group consisted of children and young adults who were at-risk for inheriting the genetic mutation that causes HD, but who were found to have a CAG repeat in the non-expanded range (gene non-expanded [GNE]).
RESULTS
Data were obtained between March 17, 2006, and February 13, 2020. There were 26 JOHD participants and 78 GNE participants who were comparable on age (16.03 vs. 14.43, respectively) and sex (53.8% female vs. 57.7% female, respectively). The mean annualized decrease in striatal volume in the JOHD group was -3.99% compared to -0.06% in the GNE (mean difference [MD], -3.93%; 95% confidence intervals [CI], [-4.98 to -2.80], FDR < 0.0001). The mean increase in the Unified Huntington's Disease Rating Scale Total Motor Score per year in the JOHD group was 7.29 points compared to a mean decrease of -0.21 point in the GNE (MD, 7.5; 95% CI, [5.71-9.28], FDR < 0·0001).
CONCLUSIONS
These findings demonstrate that structural brain imaging and clinical measures in JOHD may be potential biomarkers of disease progression for use in clinical trials. Collaborative efforts are required to validate these results in a larger cohort of patients with JOHD. © 2022 International Parkinson and Movement Disorder Society.
Identifiants
pubmed: 36318082
doi: 10.1002/mds.29251
pmc: PMC9851979
mid: NIHMS1840224
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
113-122Subventions
Organisme : NINDS NIH HHS
ID : R01-NS094387
Pays : United States
Organisme : NIMH NIH HHS
ID : P50-HD103556
Pays : United States
Organisme : NINDS NIH HHS
ID : K23 NS117736
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS055903
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD103556
Pays : United States
Organisme : NINDS NIH HHS
ID : U01 NS055903
Pays : United States
Informations de copyright
© 2022 International Parkinson and Movement Disorder Society.
Références
Lancet Neurol. 2018 Nov;17(11):986-993
pubmed: 30243861
Clin Genet. 2004 Apr;65(4):267-77
pubmed: 15025718
Lancet Neurol. 2014 Dec;13(12):1193-201
pubmed: 25453459
Mov Disord. 1996 Mar;11(2):136-42
pubmed: 8684382
J Huntingtons Dis. 2020;9(3):217-229
pubmed: 32925079
Neuroimage. 2006 Jul 1;31(3):968-80
pubmed: 16530430
JAMA Neurol. 2019 Nov 01;76(11):1375-1385
pubmed: 31403680
Cell. 1993 Mar 26;72(6):971-83
pubmed: 8458085
Neurology. 2017 Dec 12;89(24):2495-2502
pubmed: 29142089
Front Neuroinform. 2013 Nov 18;7:29
pubmed: 24302911
J Huntingtons Dis. 2019;8(2):171-179
pubmed: 31045518
Dialogues Clin Neurosci. 2016 Mar;18(1):91-8
pubmed: 27069383
Lancet Neurol. 2013 Jul;12(7):637-49
pubmed: 23664844
BMJ Open. 2013 Apr 03;3(4):
pubmed: 23558730
J Huntingtons Dis. 2019;8(2):181-193
pubmed: 30856116
Lancet Neurol. 2018 Nov;17(11):932-933
pubmed: 30243863
Neurology. 2019 Sep 3;93(10):e1021-e1030
pubmed: 31371571
Brain. 2011 Jan;134(Pt 1):137-42
pubmed: 20923788
Brain Sci. 2020 Aug 08;10(8):
pubmed: 32784364
Neurology. 2019 Apr 23;92(17):e1939-e1947
pubmed: 30971481