Gender as a Modifying Factor Influencing Myotonic Dystrophy Type 1 Phenotype Severity and Mortality: A Nationwide Multiple Databases Cross-Sectional Observational Study
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...
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| Published in | PloS one Vol. 11; no. 2; p. e0148264 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Public Library of Science
05.02.2016
Public Library of Science (PLoS) |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1932-6203 1932-6203 |
| DOI | 10.1371/journal.pone.0148264 |
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| Abstract | 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. |
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| AbstractList | 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 (>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). 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. 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 (>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). 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. 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 (>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). 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. 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. 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. 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.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.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).METHODSWe 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.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.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.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. 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 (\textgreater18y) 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 |
| Audience | Academic |
| Author | 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 |
| AuthorAffiliation | 9 Neuromuscular Reference Center, CHU Grenoble, Grenoble, France 5 Neuromuscular Reference Center, CHU Toulouse, Toulouse, France 4 Neuromuscular Reference Center, CHU Fort-de-France, Fort de France, France 7 Neuromuscular Reference Center, GH Pitié-Salpêtrière, AP-HP, Paris, France 8 Neuromuscular Reference Center, GH Est, HCL, Bron, France 12 Neuromuscular Competence Center, CHU Caen, Caen, France University of Valencia, SPAIN 20 Neuromuscular Reference Center, CHRU Lilles, Lille, France 13 Neuromuscular Reference Center, CHU Nice, Nice, France 19 Neuromuscular Competence Center, CHU Tours, Tours, France 24 CoPil, DM1 patients group, AFM-Téléthon, Evry, France 3 Direction de la Recherche et de l'Innovation, CHU Montpellier, Montpellier, France 1 Neuromuscular Reference Center, GH Henri Mondor, AP-HP, Créteil, France, INSERM U955, UPEC university, Créteil, France 18 Neuromuscular Reference Center, CHU Angers, Angers, France 22 Neuromuscular Competence Center, HIA Clermont-Tonnerre, Brest, France 2 I |
| AuthorAffiliation_xml | – name: University of Valencia, SPAIN – name: 11 Neuromuscular Reference Center, GH Timone, AP-HM, Marseille, France – name: 21 Neuromuscular Reference Center, Hôpital Marin, AP-HP, Hendaye, France – name: 8 Neuromuscular Reference Center, GH Est, HCL, Bron, France – name: 7 Neuromuscular Reference Center, GH Pitié-Salpêtrière, AP-HP, Paris, France – name: 22 Neuromuscular Competence Center, HIA Clermont-Tonnerre, Brest, France – name: 20 Neuromuscular Reference Center, CHRU Lilles, Lille, France – name: 10 Neuromuscular Reference Center, CHU Reims, Reims, France – name: 3 Direction de la Recherche et de l'Innovation, CHU Montpellier, Montpellier, France – name: 23 PMSI Division, Hox-Com Analytiques Paris, France – name: 13 Neuromuscular Reference Center, CHU Nice, Nice, France – name: 14 Neuromuscular Reference Center, CHU Bordeaux, Bordeaux, France – name: 18 Neuromuscular Reference Center, CHU Angers, Angers, France – name: 12 Neuromuscular Competence Center, CHU Caen, Caen, France – name: 15 Neuromuscular Reference Center, CHU Limoges, Limoges, France – name: 4 Neuromuscular Reference Center, CHU Fort-de-France, Fort de France, France – name: 5 Neuromuscular Reference Center, CHU Toulouse, Toulouse, France – name: 17 Neuromuscular Competence Center, CHU Rennes, Rennes, France – name: 9 Neuromuscular Reference Center, CHU Grenoble, Grenoble, France – name: 16 Neuromuscular Reference Center, CHU Nantes, Nantes, France – name: 6 Neuromuscular Competence Center, CHU Rouen, Rouen, France – name: 1 Neuromuscular Reference Center, GH Henri Mondor, AP-HP, Créteil, France, INSERM U955, UPEC university, Créteil, France – name: 24 CoPil, DM1 patients group, AFM-Téléthon, Evry, France – name: 19 Neuromuscular Competence Center, CHU Tours, Tours, France – name: 2 INSERM U1138, Centre de recherche des cordeliers, Paris Descartes university, UPMC university, Paris, France – name: 25 Human Genetic Research Unit, CHU Laval, Quebec, Canada |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26849574$$D View this record in MEDLINE/PubMed https://univ-rennes.hal.science/hal-01274908$$DView record in HAL |
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| Keywords | Cataracts Obesity Death rates Myotonic dystrophy Maternal inheritance Dysphagia Morbidity Cognitive impairment |
| Language | English |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Undefined-3 Conceived and designed the experiments: C. Dogan DH GB BE J. Puymirat. Performed the experiments: C. Dogan MDA SK RKG GB. Analyzed the data: MDA HV FR. Contributed reagents/materials/analysis tools: C. Dogan MDA RKG SK GB BE J. Puymirat. Wrote the paper: C. Dogan MDA RKG SK GB. Collected and monitored DM-Scope data: MF KA MCA ALB AB RB F. Bouhour C. Boutte F. Boyer ECS FC PC C. Desnuelle RD VDG XF HGB KG PL AM LM DM MCM ANP SP YP MP J. Pouget SS GS TS VT AU CV FZ. Managed DM1 patients Survey (FDM-S): C. Bourlier GR AG. Managed PMSI database: GC. Competing Interests: The authors have declared that no competing interests exist. |
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| Snippet | Myotonic Dystrophy type 1 (DM1) is one of the most heterogeneous hereditary disease in terms of age of onset, clinical manifestations, and severity,... Background Myotonic Dystrophy type 1 (DM1) is one of the most heterogeneous hereditary disease in terms of age of onset, clinical manifestations, and severity,... BACKGROUND: Myotonic Dystrophy type 1 (DM1) is one of the most heterogeneous hereditary disease in terms of age of onset, clinical manifestations, and... Background Myotonic Dystrophy type 1 (DM1) is one of the most heterogeneous hereditary disease in terms of age of onset, clinical manifestations, and severity,... |
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| SubjectTerms | Abnormalities Adult Biology and Life Sciences Care and treatment Cataracts Chronology Clinical trials Cognitive ability 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 |
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| Title | Gender as a Modifying Factor Influencing Myotonic Dystrophy Type 1 Phenotype Severity and Mortality: A Nationwide Multiple Databases Cross-Sectional Observational Study |
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