Survival patterns and cancer determinants in families with myotonic dystrophy type 1

Eur J Neurol. 2019 Jan;26(1):58-65. doi: 10.1111/ene.13763. Epub 2018 Sep 16.


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.

Keywords: cancer; genetic testing; mortality; myotonic dystrophy type 1; tumor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cluster Analysis
  • Family
  • Female
  • Genetic Testing
  • Humans
  • Male
  • Middle Aged
  • Myotonic Dystrophy / epidemiology*
  • Myotonic Dystrophy / genetics
  • Myotonic Dystrophy / mortality
  • Neoplasms / epidemiology*
  • Neoplasms / genetics
  • Neoplasms / mortality
  • Physical Examination
  • Registries
  • Risk Assessment
  • Surveys and Questionnaires
  • Survival Analysis
  • United Kingdom / epidemiology
  • United States / epidemiology