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Survival patterns and cancer determinants in families with myotonic dystrophy type 1
Author(s) -
Best A. F.,
Hilbert J. E.,
Wood L.,
Martens W. B.,
Nikolenko N.,
MariniBettolo C.,
Lochmüller H.,
Rosenberg P. S.,
Moxley R. T.,
Greene M. H.,
Gadalla S. M.
Publication year - 2019
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.13763
Subject(s) - medicine , myotonic dystrophy , odds ratio , family history , standardized mortality ratio , cancer , population , offspring , demography , genetics , pregnancy , environmental health , biology , sociology
Background and purpose Research indicates that patients with myotonic dystrophy type 1 ( DM 1) are at increased risk of cancer and early death. Family data may provide insights given DM 1 phenotypic heterogeneity, the broad range of non‐muscular manifestations and the usual delays in the diagnosis of DM 1. Method Family history data were collected from 397 genetically and/or clinically confirmed DM 1 patients (respondents) enrolled in the US or UK myotonic dystrophy registries. Standardized mortality ratios were calculated for DM 1 first‐degree relatives (parents, siblings and offspring) by their reported DM 1 status (affected, unaffected or unknown). For cancer‐related analyses, mixed effects logistic regression models were used to evaluate factors associated with cancer development in DM 1 families, including familial clustering. Results A total of 467 deaths and 337 cancers were reported amongst 1737 first‐degree DM 1 relatives. Mortality risk amongst relatives reported as DM 1‐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 DM 1‐affected relatives ( SMR = 2.47, P < 0.0001) and in those whose DM 1 status was unknown ( SMR = 1.60, P < 0.0001). In cancer risk analyses, risk was higher amongst families in which the DM 1 respondent had cancer (odds ratio 1.95, P = 0.0001). Unknown DM 1 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 DM 1 and in those whose DM 1 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 DM 1 and who might benefit from disease‐specific clinical care and surveillance.