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PLoS One. 2016 Feb 5;11(2):e0148264. doi: 10.1371/journal.pone.0148264. eCollection 2016.

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

Author information

1
Neuromuscular Reference Center, GH Henri Mondor, AP-HP, Créteil, France, INSERM U955, UPEC university, Créteil, France.
2
INSERM U1138, Centre de recherche des cordeliers, Paris Descartes university, UPMC university, Paris, France.
3
Direction de la Recherche et de l'Innovation, CHU Montpellier, Montpellier, France.
4
Neuromuscular Reference Center, CHU Fort-de-France, Fort de France, France.
5
Neuromuscular Reference Center, CHU Toulouse, Toulouse, France.
6
Neuromuscular Competence Center, CHU Rouen, Rouen, France.
7
Neuromuscular Reference Center, GH Pitié-Salpêtrière, AP-HP, Paris, France.
8
Neuromuscular Reference Center, GH Est, HCL, Bron, France.
9
Neuromuscular Reference Center, CHU Grenoble, Grenoble, France.
10
Neuromuscular Reference Center, CHU Reims, Reims, France.
11
Neuromuscular Reference Center, GH Timone, AP-HM, Marseille, France.
12
Neuromuscular Competence Center, CHU Caen, Caen, France.
13
Neuromuscular Reference Center, CHU Nice, Nice, France.
14
Neuromuscular Reference Center, CHU Bordeaux, Bordeaux, France.
15
Neuromuscular Reference Center, CHU Limoges, Limoges, France.
16
Neuromuscular Reference Center, CHU Nantes, Nantes, France.
17
Neuromuscular Competence Center, CHU Rennes, Rennes, France.
18
Neuromuscular Reference Center, CHU Angers, Angers, France.
19
Neuromuscular Competence Center, CHU Tours, Tours, France.
20
Neuromuscular Reference Center, CHRU Lilles, Lille, France.
21
Neuromuscular Reference Center, Hôpital Marin, AP-HP, Hendaye, France.
22
Neuromuscular Competence Center, HIA Clermont-Tonnerre, Brest, France.
23
PMSI Division, Hox-Com Analytiques Paris, France.
24
CoPil, DM1 patients group, AFM-Téléthon, Evry, France.
25
Human Genetic Research Unit, CHU Laval, Quebec, Canada.

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.

CONCLUSION:

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.

PMID:
26849574
PMCID:
PMC4744025
DOI:
10.1371/journal.pone.0148264
[Indexed for MEDLINE]
Free PMC Article

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