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Perinatal insults and neurodevelopmental disorders may impact Huntington's disease age of diagnosis.

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.

journal_name

Parkinsonism Relat Disord

journal_title

Parkinsonism & related disorders

authors

Barkhuizen M,Rodrigues FB,Anderson DG,Winkens B,REGISTRY Investigators of the European Huntington's Disease Network.,Wild EJ,Kramer BW,Gavilanes AWD

doi

10.1016/j.parkreldis.2018.05.016

subject

Has Abstract

pub_date

2018-10-01 00:00:00

pages

55-60

eissn

1353-8020

issn

1873-5126

pii

S1353-8020(18)30246-3

journal_volume

pub_type

杂志文章,多中心研究

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Perinatal insults and neurodevelopmental disorders may impact Huntington's disease age of diagnosis.