Gender as a Modifying Factor Influencing Myotonic Dystrophy Type 1 Phenotype Severity and Mortality: A Nationwide Multiple Databases Cross-Sectional Observational Study

Abstract

BackgroundMyotonic Dystrophy type 1 (DM1) is one of the most heterogeneous hereditary disease in terms of age of onset, clinical manifestations, and severity, challenging both medical management and clinical trials. The CTG expansion size is the main factor determining the age of onset although no factor can finely predict phenotype and prognosis. Differences between males and females have not been specifically reported. Our aim is to study gender impact on DM1 phenotype and severity.MethodsWe first performed cross-sectional analysis of main multiorgan clinical parameters in 1409 adult DM1 patients (>18y) from the DM-Scope nationwide registry and observed different patterns in males and females. Then, we assessed gender impact on social and economic domains using the AFM-Téléthon DM1 survey (n = 970), and morbidity and mortality using the French National Health Service Database (n = 3301).ResultsMen more frequently had (1) severe muscular disability with marked myotonia, muscle weakness, cardiac, and respiratory involvement; (2) developmental abnormalities with facial dysmorphism and cognitive impairment inferred from low educational levels and work in specialized environments; and (3) lonely life. Alternatively, women more frequently had cataracts, dysphagia, digestive tract dysfunction, incontinence, thyroid disorder and obesity. Most differences were out of proportion to those observed in the general population. Compared to women, males were more affected in their social and economic life. In addition, they were more frequently hospitalized for cardiac problems, and had a higher mortality rate.ConclusionGender is a previously unrecognized factor influencing DM1 clinical profile and severity of the disease, with worse socio-economic consequences of the disease and higher morbidity and mortality in males. Gender should be considered in the design of both stratified medical management and clinical trials.

The UK Myotonic Dystrophy Patient Registry: facilitating and accelerating clinical research

“…For example, the data presented support a recent study indicating gender differences in DM1 [8]. Similar to this study, men had higher frequencies of severe myotonia, mobility impairments, cardiac abnormalities, and non-invasive ventilation, whereas women presented more often with cataracts.…”

Validation of plasma microRNAs as biomarkers for myotonic dystrophy type 1

“…While the reason for this gender difference is unknown, it is not surprising since gender is emerging as an important factor influencing DM1 clinical profile3031. Of note, it has been found that miR-133b stimulates ovarian estradiol synthesis32.…”

Cognitive impairment and quality of life in patients with myotonic dystrophy type 1

“…Patients were recruited from 5 hospitals (National Hospital Organization [NHO] Toneyama National Hospital, NHO Okinawa National Hospital, NHO Akita National Hospital, Yokohama Rosai Hospital, and Osaka University Hospital). Although no consensus regarding the clinical classification of DM1 exists, we classified patients into 4 clinical forms according to the age at onset using criteria from a recent study; clinical onset from 1 month to 10 years of age = infantile, 11–20 years = juvenile, 21–40 years = adult, and >40 years = late onset . The number of CTG repeats was assessed by polymerase chain reaction and Southern blotting.…”