Discussion
This report describes the DM-Scope registry, an innovative concept that overcomes most of RD registries limitations. Indeed, health authorities pointed to main limitations of RD registries including underreporting of outcomes, missing data, and/or inadequate follow-up. Robustness of gathered data depends on the quality of data entry, the number of enrolled patients, the diversity of their demographic and disease characteristics, including age-annotated manifestations, and the retention of recruited patients [
1‐
4].
DM-Scope registry overall model is based on (1) an innovative IT platform that provides tools for clinicians to facilitate the management of DM patients, and on (2) the network of neuromuscular expert centres established by the national RDs plan in France. The registry federates RD expert physicians, from 55 French neuromuscular expert centres, and promotes a longitudinal standardised data collection. To our knowledge, such platform is a unique example that helps to optimize medical care as well as facilitate research in RD. By enabling the input of multidisciplinary expert physicians and limiting the contribution of cognitively impaired DM patients, this registry ensures highest quality of data. While other DM registries have been established [
64] the DM-Scope registry is the largest one with almost 3000 DM enrolled patients accounting for more than 20% of overall registered DM patients internationally [
53]. Furthermore, the registry collects the whole range of demographic and phenotypic characteristics of this RD condition. Indeed, standardized data span from congenital patients at birth to late onset adult patients. In addition, the platform includes three levels-quality insurance procedure.
The registry coverage is nationwide though some regions are under-represented. This is likely related to the activity of the neuromuscular expert centres and more recent partnered centres should homogenise the national distribution in the future. Studies to assess the DM prevalence are limited [
13] and the exact prevalence in France is unknown. In addition, the DM disease is not listed for genetic screening in most countries. Therefore national coverage of our registry contributes to estimate the distribution of DM individuals and regional differences. Some differences were observed in the relative distribution of DM patients according to the general population density in some geographic areas suggesting that the prevalence of DM is uneven across France. For example, in the Basque region a high DM1 frequency was observed which is consistent with the report by López de Munain et al. [
45]. To confirm such regional disparities in France, we plan to analyse complementary data from the national BAMARA registry [
46]. It should be noted that DM-Scope and BAMARA registries are not designed for prevalence studies since they are not intended to collect the complete disease population.
Recently, we decided to record death status which allows (1) to estimate the severity of the disease; (2) to minimise bias in cross-sectional studies due to loss of follow-up due to death; (3) for patient screening and enrolment in clinical trials; (4) to assess various prognostic factors of death. Survival analyses in DM are scarce with no recent population cohort data existing. Our results showed an annual frequency of death consistent with previous reports [
65]. In our case, the number of deceased patients is likely under-estimated since the vital status recording was more recently introduced leading to no record of death being reported by many centres. An accurate identification of death is limited since it is not part of annual clinical follow-up management. We expect to further improve the registry by identifying patients not seen (> 3 years) by clinician determination of the patient status: lost to follow-up vs death. In addition, complementary analyses from administrative national databases [
66] will significantly improve survival estimations.
As part of the national RD plan, the DM-Scope registry will allow longitudinal comparison of medical practice between RD expert centres with the purpose of promoting a harmonization of DM medical care nationally as well as contributing to healthcare guidelines for DM.
The DM-Scope Registry covers the large clinical and genetic spectrum of DM patients [
14,
16] with the representation of all social and professional conditions. The registry provides opportunities to characterize large DM cohorts of adults or children, to clarify genotype-phenotype correlations, to study the social and professional consequences of DM as well as to compare the DM1 and DM2 genetic entities. While encompassing all disease organ and system involvement, the registry currently lacks items describing the cognitive impairment. Over the past few years, international workshops [
67,
68] have focused on how to assess central nervous system involvement. Some time-consuming neuropsychological tests are currently discussed and require validation for future integration into registry dataset. Missing data are mainly related to optional items and seem randomly distributed.
The DM-Scope registry has drawbacks including (1) the lack of items related to the cognitive impairment, (2) the underreporting of deceased cases, and (3) missing data.
Our platform has already proven to be a key instrument for promoting clinical studies and generating data for medical care guidance in DM1. In fact, the registry substantially facilitated DM translational research by (1) refining the DM1 clinical classification; (2) accessing to available biomaterials for molecular basic research studies; (3) the design and the recruitment of patients in both observational and interventional studies; and (4) producing evidence-based material for care guidelines in adult and childhood DM populations. Future longitudinal analyses from the DM-Scope registry will be conducted to refine the clinical characteristics of the DM population.
The transferable strengths of the registry rely in the fact that it is a shareable and interoperable framework which promotes multicentre high quality data collection in a large population. In this way, the DM-Scope registry has recently evolved into an international consortium (named iDM-Scope) to harmonise the French and Quebec cohorts. Such data standardization allows the comparison of DM characteristics in two different populations. Data harmonization helps to improve translational research including natural history studies, biomarker identification and outcome measures and facilitates the recruitment of patients in upcoming transnational multicentre trials. It represents a first step to contribute to cross-border healthcare in DM. In addition, DM-scope concept can serve as a model to other RDs.
Acknowledgments
We would like to thank all of the patients and staff members that participated in collecting data at clinical sites, particularly: Sylvie Brimont, Margaret Bruey, Sylvie Estrade, Katia Gillo, Maryse, Maclet-bourrienne, Bénédicte Pontier, Magalie Pointud, Pascale Poitou, Candice Rudelle and Aurore Siffert. We would like also to thank Hélène Moussu, Catherine Eng, Caroline Stalens, Melinda Gyenge and Simone Birnbaum who reviewed the manuscript. We are grateful to the AFM-Téléthon for its financial support.
The French myotonic dystrophy clinical research network of Filnemus is composed of (The group has to be searchable through their individual PubMed records): ARNE BES Marie Christine (Neurologie, Pôle neurosciences, Hôpital Pierre-Paul Riquet, Toulouse, France), ATTARIAN Shahram (Service de Neurologie Hôpital de La Timone 1, Marseille, France) AUBE-NATHIER Anne-Catherine (Consultation multidisciplinaire maladies neuromusculaires pour adultes Département de neurologie, CHU d’Angers, France), AUDIC Frédérique, (Service de neurologie pédiatrique, pneumologie pédiatrique et médecine infantile, Hôpital de La Timone, Marseille, France), BACH Nathalie (Service de pédiatrie médicale, pôle Femme Enfant, CHU, Caen, France), BARNERIAS Christine (Consultation myologie, Cliniques des maladies du développement, Hôpital Necker-Enfants Malades, Paris, France), BEDAT-MILLET Anne-Laure (Service de neurologie, CHU Nicolle, ROUEN Cedex, France), BEHIN Anthony (Institut de myologie, hôpital Pitié-Salpêtrière, Paris, France), BELLANCE Remi (Centre hospitalier universitaire Fort de France), BENYAOU Rabah (Institut de myologie, hôpital Pitié-Salpêtrière, Paris, France), BOMBARD Véronique (Service de médecine physique et de réadaptation, Hôpital Sébastopol, Reims, France), BOUHOUR Françoise (Centre SLA-service d’électroneuromyographie et pathologies neuromusculaires, hôpital Pierre Wertheimer, CHU de Lyon, BRON, France), BOUTTE Celia (Pôle de psychiatrie et neurologie, CHU de Grenoble site Nord-Hôpital Albert Michallon, Grenoble, France), BOYER François (Service de médecine physique et de réadaptation, Hôpital Sébastropol, Reims), CANCES Claude (Service de pédiatrie - Neurologie et infectiologie, Pôle enfants, Hôpital des enfants, CHU Purpan, Toulouse, France), CHABROL Brigitte (Service de neurologie pédiatrique, pneumologie pédiatrique et médecine infantile, Hôpital de La Timone, Marseille, France), CHANSON Jean-Baptiste (Hôpital de jour - Neurologie -Pôle tête-cou / CETD, Hôpital de Hautepierre, Strasbourg, France), CHAPON Françoise (Laboratoire d’Anatomie Pathologie – Neuropathologie CHU Hôpital Côte de Nacre, Caen, France), CHASSERIAU Raphaële (Laboratoire d’explorations fonctionnelles CHU de Nantes, France), CINTAS Pascal (Neurologie, Pôle neurosciences, Hôpital Pierre-Paul Riquet, Toulouse, France), COBO Ana-Maria (Hôpital Marin, Hendaye. France), COLOMBERT Vanessa (Centre hospitalier Bretagne Atlantique, Vannes, France), CRUZ Marie-Carmen (Neurologie, Pôle neurosciences, Hôpital Pierre-Paul Riquet, Toulouse, France), CUISSET Jean-Marie (Service de neuropédiatrie, Hôpital Roger-Salengro, Lille, France), DESCHAMPS Romain (Centre hospitalier universitaire, unité de neuromyologie, Fort de France cedex), DESGUERRE Isabelle (Consultation myologie, Cliniques des maladies du développement, Hôpital Necker-Enfants Malades, Paris, France), DURIGNEUX Julien (Pôle mère-enfant, neuropédiatrie et neurochirgurgie de l’enfant, CHU d’Angers, France), DUVAL Fanny (Service de neurologie- Hôpital Pellegrin, Bordeaux, France), ESPIL Caroline (Service de pédiatrie médicale, Hôpital Pellegrin, Bordeaux, France), FAFIN Catherine (Hôpitaux pédiatriques de Nice CHU-Lenval, Nice, France), FEASSON Léonard (Consultation Médecine physique et réadaptation enfant, Hôpital Bellevue, Saint-Etienne, France), FRADIN Mélanie (Pôle de pédiatrie médico-chirurgicale et génétique clinique CHU de Rennes - Hôpital Sud, Rennes, France), FURBY Alain (Consultation Médecine physique et réadaptation enfant, Hôpital Bellevue Saint-Etienne, France), GOLDENBERG Alice (Unité de Génétique Clinique, CHU Nicolle, Rouen, France), GROTTO Sarah (Unité de Génétique Clinique, CHU Nicolle, Rouen, France), GHORAB Karima (Service de neurologie C H U Dupuytren 2, Limoges, France), GUYANT-MARECHAL Lucie (Unité de Génétique Clinique, CHU Nicolle, Rouen, France), HERON Delphine (Institut de myologie, hôpital Pitié-Salpêtrière, Paris, France), ISAPOF Arnaud (Service de neuropédiatrie et pathologie du développement, Hôpital Trousseau, Paris, France), JACQUIN-PIQUES Agnes (Service de neurophysiologie enfants et adultes, Hôpital F. Mitterrand, Dijon, France), JOURNEL Hubert (CHBA Centre hospitalier Bretagne Atlantique, Vannes, France), LAFORET Pascal (Institut de myologie, hôpital Pitié-Salpêtrière, Paris, France), LAGRUE Emmanuelle (Service de neuropédiatrie et handicaps, CHRU Clocheville, Tours, Fra,ce), LAROCHE-RAYNAUD Cécile (Hôpital de la mère et de l’enfant, Dominique Larrey, Limoges, France), LAUGEL Vincent (Service de pédiatrie médico-chirurgicale, Hôpital de Hautepierre, Strasbourg, France), LEBEAU Françoise (Service de neurologie CHU Dupuytren 2, Limoges, France), MAGOT Armelle (Laboratoire d’explorations fonctionnelles, Hôtel Dieu 1, Nantes, France), MANEL Véronique (Exploration fonctionnelle neuropédiatrique, Hôpital Femme Mère enfant, Bron, France), MAYER Michèle (Service de neuropédiatrie et pathologie du développement, Hôpital Trousseau, Paris, France), MERCIER Sandra (Laboratoire d’explorations fonctionnelles, Hôtel Dieu1, Nantes, France), MENARD Dominique (Consultation neuromusculaire, CHU Hôpital Pontchaillou 2, Rennes, France), MICHAUD Maud (Service de neurologie, hôpital central, Nancy. Paris), MINOT Marie-Christine (Consultation neuromusculaire, CHU Hôpital Pontchaillou 2, Rennes, France), MORALES Raul-Juntas (Pôle neuroscience tête et cou - Hôpital Gui de Chauliac Montpellier, France), NADAJ-PAKLEZA Aleksandra (Consultation multidisciplinaire maladies neuromusculaires pour adultes Département de neurologie, Hôpital Larrey, Angers, France), NOURY Jean-Baptiste (Service de neurologie. Hôpital d’instruction des armées Clermont-Tonnerre, Brest. France), PASQUIER Laurent (Génétique médicale CHU Hôpital Sud, Rennes, France), PELLIEUX Sybille (Service de médecine physique et réadaptation, Hôpital Trousseau Tours, France), PEREON Yann (Laboratoire d’explorations fonctionnelles, Hôtel Dieu Nantes, France), PERRIER Julie (Laboratoire d’explorations fonctionnelles, Hôtel Dieu Nantes, France), PEUDENIER Sylviane (Département de pédiatrie et département de génétique médicale, Hôpital Morvan, Brest, France), PREUDHOMME Marguerite (Service de médecine et de réadaptation, Centre Hospitalier Régional Universitaire de Lille2, Lille, France), POUGET Jean (Service de Neurologie Hôpital de La Timone 1, Marseille, France), QUIJANO-ROY Susana (Service de Neurologie et réanimation pédiatriques CHU Paris IdF Ouest - Hôpital Raymond Poincaré, Garches, France), RAGOT-MANDRY Sylvie (Service d’explorations fonctionnelles pédiatriques, Hôpital de Brabois, Vandœuvre-Lès-Nancy, France), RICHELME Christian (Service de de pédiatrie et de neuropédiatrie, Hôpital l’Archet 2, Pôle Femme Mère Enfant, Nice, France), RIVIER François (Département de neuropédiatrie, Hôpital Gui de Chauliac, Montpellier, France), SABOURAUD Pascal (Service de pédiatrie A - Unité de neurologie pédiatrique. American Memorial Hospital, Reims, France), SACCONI Sabrina (Système Nerveux Périphérique, Muscle et SLA. Pôle Neurosciences. Hôpital Pasteur 2, Nice, France), SALORT–CAMPANA Emmanuelle (Centre de Référence Maladies Neuromusculaires et SLA Hôpital de la Timone, Marseille Cedex 20, France), SARRET Catherine (Pôle de pédiatrie, Hôpital d’Estaing, Clermont-Ferrand, France), SCHAEFFER Stéphane (Laboratoire d’Anatomie Pathologie – Neuropathologie CHU Hôpital Côte de Nacre, Caen, France), SOLE Guilhem (Service de neurologie- Hôpital Pellegrin, Bordeaux, France), STOJKOVIC Tanya (Institut de myologie, hôpital Pitié-Salpêtrière, Paris, France), TAITHE Frédéric (Service de neurologie, CHU,Clermont-Ferrand, France), TESTARD Hervé (Pôle de Psychiatrie, Neurologie et Rééducation Neurologique, CHU Grenoble Alpes, Grenoble, France), TIFFEREAU Vincent (Service de médecine et de réadaptation, Centre Hospitalier Régional Universitaire de Lille2,Lille.France), URTIZBEREA Andoni (Hôpital Marin, Hendaye, France), VANHULLE Catherine (Service de neurologie pédiatrique. Pavillon Femme, mère et enfant. Hôpital Charles Nicolle, Rouen. France), VIAL Christophe (Centre SLA-service d’électroneuromyographie et pathologies neuromusculaires, hôpital Pierre Wertheimer, CHU de Lyon, BRON, France), WALTHER-LOUVIER Ulrike (Département de neuropédiatrie, Hôpital Gui de Chauliac, Montpellier, France), ZAGNOLI Fabien (Service de neurologie. Hôpital d’instruction des armées Clermont-Tonnerre, Brest. France).