Browse by author
Lookup NU author(s): Lindsay Wood, Dr Nikoletta Nikolenko, Professor Chiara Marini Bettolo, Professor Hanns Lochmuller
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
© 2018 EAN. This article has been contributed to by US Government employees and their work is in the public domain in the USA Background and purpose: Research indicates that patients with myotonic dystrophy type 1 (DM1) are at increased risk of cancer and early death. Family data may provide insights given DM1 phenotypic heterogeneity, the broad range of non-muscular manifestations and the usual delays in the diagnosis of DM1. Method: Family history data were collected from 397 genetically and/or clinically confirmed DM1 patients (respondents) enrolled in the US or UK myotonic dystrophy registries. Standardized mortality ratios were calculated for DM1 first-degree relatives (parents, siblings and offspring) by their reported DM1 status (affected, unaffected or unknown). For cancer-related analyses, mixed effects logistic regression models were used to evaluate factors associated with cancer development in DM1 families, including familial clustering. Results: A total of 467 deaths and 337 cancers were reported amongst 1737 first-degree DM1 relatives. Mortality risk amongst relatives reported as DM1-unaffected was comparable to that of the general population [standardized mortality ratio (SMR) 0.82, P = 0.06], whilst significantly higher mortality risks were noted in DM1-affected relatives (SMR = 2.47, P < 0.0001) and in those whose DM1 status was unknown (SMR = 1.60, P < 0.0001). In cancer risk analyses, risk was higher amongst families in which the DM1 respondent had cancer (odds ratio 1.95, P = 0.0001). Unknown DM1 status in the siblings (odds ratio 2.59, P = 0.004) was associated with higher cancer risk. Conclusion: There is an increased risk of death, and probably cancer, in relatives with DM1 and in those whose DM1 status is unknown. This suggests a need to perform a careful history and physical examination, supplemented by genetic testing, to identify family members at risk for DM1 and who might benefit from disease-specific clinical care and surveillance.
Author(s): Best AF, Hilbert JE, Wood L, Martens WB, Nikolenko N, Marini-Bettolo C, Lochmuller H, Rosenberg PS, Moxley RT, Greene MH, Gadalla SM
Publication type: Article
Publication status: Published
Journal: European Journal of Neurology
Year: 2018
Volume: 26
Issue: 1
Pages: 58-65
Print publication date: 01/01/2019
Online publication date: 27/07/2018
Acceptance date: 21/06/2018
ISSN (print): 1351-5101
ISSN (electronic): 1468-1331
Publisher: Blackwell Publishing Ltd
URL: https://doi.org/10.1111/ene.13763
DOI: 10.1111/ene.13763
Altmetrics provided by Altmetric
