title: Gender as a Modifying Factor Influencing Myotonic Dystrophy Type 1 Phenotype Severity and Mortality: A Nationwide Multiple Databases Cross-Sectional Observational Study.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Neuromuscular Reference Center, GH Henri Mondor, AP-HP, Créteil, France, INSERM U955, UPEC university, Créteil, France.
authors: Celine
authors: C
authors: Dogan
authors: Neuromuscular Reference Center, GH Henri Mondor, AP-HP, Créteil, France, INSERM U955, UPEC university, Créteil, France.|INSERM U1138, Centre de recherche des cordeliers, Paris Descartes university, UPMC university, Paris, France.
authors: Marie
authors: M
authors: De Antonio
authors: Direction de la Recherche et de l'Innovation, CHU Montpellier, Montpellier, France.
authors: Dalil
authors: D
authors: Hamroun
authors: Neuromuscular Reference Center, GH Henri Mondor, AP-HP, Créteil, France, INSERM U955, UPEC university, Créteil, France.
authors: Hugo
authors: H
authors: Varet
authors: Neuromuscular Reference Center, GH Henri Mondor, AP-HP, Créteil, France, INSERM U955, UPEC university, Créteil, France.
authors: Marianne
authors: M
authors: Fabbro
authors: Neuromuscular Reference Center, GH Henri Mondor, AP-HP, Créteil, France, INSERM U955, UPEC university, Créteil, France.
authors: Felix
authors: F
authors: Rougier
authors: Neuromuscular Reference Center, CHU Fort-de-France, Fort de France, France.
authors: Khadija
authors: K
authors: Amarof
authors: Neuromuscular Reference Center, CHU Toulouse, Toulouse, France.
authors: Marie-Christine
authors: MC
authors: Arne Bes
authors: Neuromuscular Competence Center, CHU Rouen, Rouen, France.
authors: Anne-Laure
authors: AL
authors: Bedat-Millet
authors: Neuromuscular Reference Center, GH Pitié-Salpêtrière, AP-HP, Paris, France.
authors: Anthony
authors: A
authors: Behin
authors: Neuromuscular Reference Center, CHU Fort-de-France, Fort de France, France.
authors: Remi
authors: R
authors: Bellance
authors: Neuromuscular Reference Center, GH Est, HCL, Bron, France.
authors: Françoise
authors: F
authors: Bouhour
authors: Neuromuscular Reference Center, CHU Grenoble, Grenoble, France.
authors: Celia
authors: C
authors: Boutte
authors: Neuromuscular Reference Center, CHU Reims, Reims, France.
authors: François
authors: F
authors: Boyer
authors: Neuromuscular Reference Center, GH Timone, AP-HM, Marseille, France.
authors: Emmanuelle
authors: E
authors: Campana-Salort
authors: Neuromuscular Competence Center, CHU Caen, Caen, France.
authors: Françoise
authors: F
authors: Chapon
authors: Neuromuscular Reference Center, CHU Toulouse, Toulouse, France.
authors: Pascal
authors: P
authors: Cintas
authors: Neuromuscular Reference Center, CHU Nice, Nice, France.
authors: Claude
authors: C
authors: Desnuelle
authors: Neuromuscular Reference Center, CHU Fort-de-France, Fort de France, France.
authors: Romain
authors: R
authors: Deschamps
authors: Neuromuscular Competence Center, CHU Rouen, Rouen, France.
authors: Valerie
authors: V
authors: Drouin-Garraud
authors: Neuromuscular Reference Center, CHU Bordeaux, Bordeaux, France.
authors: Xavier
authors: X
authors: Ferrer
authors: Neuromuscular Reference Center, GH Est, HCL, Bron, France.
authors: Helene
authors: H
authors: Gervais-Bernard
authors: Neuromuscular Reference Center, CHU Limoges, Limoges, France.
authors: Karima
authors: K
authors: Ghorab
authors: Neuromuscular Reference Center, GH Pitié-Salpêtrière, AP-HP, Paris, France.
authors: Pascal
authors: P
authors: Laforet
authors: Neuromuscular Reference Center, CHU Nantes, Nantes, France.
authors: Armelle
authors: A
authors: Magot
authors: Neuromuscular Reference Center, CHU Limoges, Limoges, France.
authors: Laurent
authors: L
authors: Magy
authors: Neuromuscular Competence Center, CHU Rennes, Rennes, France.
authors: Dominique
authors: D
authors: Menard
authors: Neuromuscular Competence Center, CHU Rennes, Rennes, France.
authors: Marie-Christine
authors: MC
authors: Minot
authors: Neuromuscular Reference Center, CHU Angers, Angers, France.
authors: Aleksandra
authors: A
authors: Nadaj-Pakleza
authors: Neuromuscular Competence Center, CHU Tours, Tours, France.
authors: Sybille
authors: S
authors: Pellieux
authors: Neuromuscular Reference Center, CHU Nantes, Nantes, France.
authors: Yann
authors: Y
authors: Pereon
authors: Neuromuscular Reference Center, CHRU Lilles, Lille, France.
authors: Marguerite
authors: M
authors: Preudhomme
authors: Neuromuscular Reference Center, GH Timone, AP-HM, Marseille, France.
authors: Jean
authors: J
authors: Pouget
authors: Neuromuscular Reference Center, CHU Nice, Nice, France.
authors: Sabrina
authors: S
authors: Sacconi
authors: Neuromuscular Reference Center, CHU Bordeaux, Bordeaux, France.
authors: Guilhem
authors: G
authors: Sole
authors: Neuromuscular Reference Center, GH Pitié-Salpêtrière, AP-HP, Paris, France.
authors: Tanya
authors: T
authors: Stojkovich
authors: Neuromuscular Reference Center, CHRU Lilles, Lille, France.
authors: Vincent
authors: V
authors: Tiffreau
authors: Neuromuscular Reference Center, Hôpital Marin, AP-HP, Hendaye, France.
authors: Andoni
authors: A
authors: Urtizberea
authors: Neuromuscular Reference Center, GH Est, HCL, Bron, France.
authors: Christophe
authors: C
authors: Vial
authors: Neuromuscular Competence Center, HIA Clermont-Tonnerre, Brest, France.
authors: Fabien
authors: F
authors: Zagnoli
authors: PMSI Division, Hox-Com Analytiques Paris, France.
authors: Gilbert
authors: G
authors: Caranhac
authors: CoPil, DM1 patients group, AFM-Téléthon, Evry, France.
authors: Claude
authors: C
authors: Bourlier
authors: CoPil, DM1 patients group, AFM-Téléthon, Evry, France.
authors: Gerard
authors: G
authors: Riviere
authors: CoPil, DM1 patients group, AFM-Téléthon, Evry, France.
authors: Alain
authors: A
authors: Geille
authors: Neuromuscular Reference Center, GH Henri Mondor, AP-HP, Créteil, France, INSERM U955, UPEC university, Créteil, France.
authors: Romain K
authors: RK
authors: Gherardi
authors: Neuromuscular Reference Center, GH Pitié-Salpêtrière, AP-HP, Paris, France.
authors: Bruno
authors: B
authors: Eymard
authors: Human Genetic Research Unit, CHU Laval, Quebec, Canada.
authors: Jack
authors: J
authors: Puymirat
authors: INSERM U1138, Centre de recherche des cordeliers, Paris Descartes university, UPMC university, Paris, France.
authors: Sandrine
authors: S
authors: Katsahian
authors: Neuromuscular Reference Center, GH Henri Mondor, AP-HP, Créteil, France, INSERM U955, UPEC university, Créteil, France.
authors: Guillaume
authors: G
authors: Bassez
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D016208:Databases, Factual; D005260:Female; D006801:Humans; D008297:Male; D009223:Myotonic Dystrophy / Q000453:epidemiology* / Q000401:mortality; D010641:Phenotype; D017678:Sex Distribution; D012959:Socioeconomic Factors