Genotype and other determinants of respiratory function in myotonic dystrophy type 1.

New treatments are being developed for myotonic dystrophy type 1 (DM1). To evaluate their efficacy, knowledge about the natural history of respiratory dysfunction and its relationship with the genotype will be crucial. Also needed is information on factors predicting the time-course of respiratory function in DM1. Using data from 283 patients, we built a segmented linear mixed-effects regression model to assess respiratory function changes over time. Respiratory variables associated with the CTG repeat number were identified by multivariate linear regression analysis. Cox proportional-hazards regression was used to estimate hazard ratios (HRs) for starting non-invasive ventilation (NIV). Higher CTG repeat number was associated with peak cough flow impairment (p = 0.007) and with lower values for maximal inspiratory pressure (p <0.0001) and upright vital capacity. A vital capacity decline over time was associated with older age at first evaluation (p <0.0001), higher CTG repeat number (p <0.0001), and higher baseline body mass index (p = 0.0004). NIV initiation was associated with lower peak cough flow (p <0.001) after age and PaCO adjustment. Earlier and closer monitoring with routine peak cough flow determination in adults with congenital DM1, combined with weight control, may diminish the risk of respiratory complications and optimise other aspects of management.