Journal Article

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

Preudhomme, Marguerite, De Antonio, Marie, Bedat-Millet, Anne-Laure, Laforet, Pascal, Pereon, Yann, Puymirat, Jack, Magot, Armelle, Deschamps, Romain, Gervais-Bernard, Helene, Bouhour, Françoise, Urtizberea, Andoni, Dogan, Celine, Ferrer, Xavier, Stojkovich, Tanya, Caranhac, Gilbert, Zagnoli, Fabien, Ghorab, Karima, Cintas, Pascal, Drouin-Garraud, Valerie, Fabbro, Marianne, Desnuelle, Claude, Sole, Guilhem, Chapon, Françoise, Arne Bes, Marie-Christine, Gherardi, Romain K., Riviere, Gerard, Magy, Laurent, Campana-Salort, Emmanuelle, Vial, Christophe, Geille, Alain, Amarof, Khadija, Behin, Anthony, Katsahian, Sandrine, Eymard, Bruno, Pellieux, Sybille, Tiffreau, Vincent, Boyer, François, Bellance, Remi, Bassez, Guillaume, Nadaj-Pakleza, Aleksandra, Rougier, Felix, Hamroun, Dalil, Minot, Marie-Christine, Boutte, Celia, Bourlier, Claude, Pouget, Jean, Sacconi, Sabrina, Varet, Hugo, Menard, Dominique

2016

Overview

Myotonic 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. We first performed cross-sectional analysis of main multiorgan clinical parameters in 1409 adult DM1 patients (>18 y) 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). Men 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. Gender 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Abnormalities / Adult / Biology and Life Sciences / Care and treatment / Cataracts / Chronology / Clinical trials / Cognitive ability / Cognitive impairment / Complications and side effects / Cross-Sectional Studies / Databases, Factual / Development and progression / Digestive tract / Dysphagia / Dystrophy / Economic conditions / Economics / Female / Females / Gastrointestinal tract / Gender differences / Gene expression / Genetics / Genotype & phenotype / Health services / Heart diseases / Human genetics / Humans / Impact analysis / Kinases / Life Sciences / Male / Males / Medical research / Medicine and Health Sciences / Morbidity / Mortality / Muscular dystrophy / Myotonia / Myotonic dystrophy / Myotonic Dystrophy - epidemiology / Myotonic Dystrophy - mortality / Neurology / Obesity / Observational studies / Patient outcomes / People and Places / Phenotype / Protein kinases / Santé publique et épidémiologie / Sex Distribution / Socioeconomic Factors / Studies / Thyroid / Trinucleotide repeat diseases