eprintid: 10048791
rev_number: 33
eprint_status: archive
userid: 608
dir: disk0/10/04/87/91
datestamp: 2018-05-21 10:09:50
lastmod: 2021-09-26 22:37:56
status_changed: 2018-12-12 14:36:01
type: article
metadata_visibility: show
creators_name: Barkhuizen, M
creators_name: Brogueira Rodrigues, FA
creators_name: Anderson, DG
creators_name: Winkens, B
creators_name: REGISTRY Investigators of the European Huntington's Disease Netw, 
creators_name: Wild, EJ
creators_name: Kramer, BW
creators_name: Gavilanes, AWD
title: Perinatal insults and neurodevelopmental disorders may impact Huntington's disease age of diagnosis
ispublished: pub
divisions: UCL
divisions: B02
divisions: C07
divisions: D07
divisions: F86
keywords: Huntington's disease; Neonatal; Developmental disorders; Epidemiological; Modifier
note: © 2018 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
abstract: INTRODUCTION: 
The age of diagnosis of Huntington's disease (HD) varies among individuals with the same HTT CAG repeat expansion size. We investigated whether early-life events, like perinatal insults or neurodevelopmental disorders, influence the diagnosis age.

METHODS: 
We used data from 13,856 participants from REGISTRY and Enroll-HD, two large international multicenter observational studies. Disease-free survival analyses of mutation carriers with an HTT CAG repeat expansion size above and including 36 were computed through Kaplan-Meier estimates of median time until an HD diagnosis. Comparisons between groups were computed using a Cox proportional hazard survival model adjusted for CAG-repeat expansion length. We also assessed whether the group effect depended on gender and the affected parent.

RESULTS: 
Insults in the perinatal period were associated with an earlier median age of diagnosis of 45.00 years (95%CI: 42.07–47.92) compared to 51.00 years (95%CI: 50.68–51.31) in the reference group, with a CAG-adjusted hazard ratio of 1.61 (95%CI: 1.26–2.06). Neurodevelopmental disorders were also associated with an earlier median age of diagnosis than the reference group of 47.00 years (95% CI: 43.38–50.62) with a CAG-adjusted hazard ratio of 1.42 (95%CI: 1.16–1.75). These associations did not change significantly with gender or affected parent.

CONCLUSIONS: 
These results, derived from large observational datasets, show that perinatal insults and neurodevelopmental disorders are associated with earlier ages of diagnosis of magnitudes similar to the effects of known genetic modifiers of HD. Given their clear temporal separation, these early events may be causative of earlier HD onset, but further research is needed to prove causation.
date: 2018-05-18
date_type: published
publisher: Elsevier
official_url: https://doi.org/10.1016/j.parkreldis.2018.05.016
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
article_type_text: Article
verified: verified_manual
elements_id: 1556748
doi: 10.1016/j.parkreldis.2018.05.016
lyricists_name: Brogueira Rodrigues, Filipe
lyricists_name: Wild, Edward
lyricists_id: FBROG17
lyricists_id: EJWIL36
actors_name: Brogueira Rodrigues, Filipe
actors_id: FBROG17
actors_role: owner
full_text_status: public
publication: Parkinsonism and Related Disorders
volume: 55
pagerange: 55-60
issn: 1353-8020
citation:        Barkhuizen, M;    Brogueira Rodrigues, FA;    Anderson, DG;    Winkens, B;    REGISTRY Investigators of the European Huntington's Disease Netw;    Wild, EJ;    Kramer, BW;           Barkhuizen, M;  Brogueira Rodrigues, FA;  Anderson, DG;  Winkens, B;  REGISTRY Investigators of the European Huntington's Disease Netw;  Wild, EJ;  Kramer, BW;  Gavilanes, AWD;   - view fewer <#>    (2018)    Perinatal insults and neurodevelopmental disorders may impact Huntington's disease age of diagnosis.                   Parkinsonism and Related Disorders , 55    pp. 55-60.    10.1016/j.parkreldis.2018.05.016 <https://doi.org/10.1016/j.parkreldis.2018.05.016>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10048791/7/Brogueira%20Rodrigues%20_Perinatal%20insults%20and%20neurodevelopmental%20disorders%20may%20impact%20Huntington%27s%20disease%20age%20of%20diagnosis_VoR.pdf