10 years of CEMARA database in the AnDDI-Rares network: a unique resource facilitating research and epidemiology in developmental disorders in France
Authors: Messiaen Claude , Racine Caroline , Khatim Ahlem , Soussand Louis , Odent Sylvie , Lacombe Didier , Manouvrier Sylvie , Edery Patrick , Sigaudy Sabine , Geneviève David , Thauvin-Robinet Christel , Pasquier Laurent , Petit Florence , Rossi Massimiliano , Willems Marjolaine , Attié-Bitach Tania , Roux-Levy Pierre-Henry , Demougeot Laurent , Slama Lilia Ben , Landais Paul ,   the AnDDI-Rares network, Leheup Bruno , Doco-Fenzy Martine , Poirsier Céline , Spodenkiewicz Marta , Lissy Lola , Lannoy Audrey , Shaefer Elise , Chehadeh Salima El , Amiel Jeanne , Mignot Cyril , Melki Judith , Whalen Sandra , Lackmy Marilyn Irène , Funalot Benoit , Morin Gilles , Gérard Marion , Gruchy Nicolas , Molin Arnaud , Toutain Annick , Arpin Stéphanie , Blesson Sophie , Jeanne Médéric , Isidor Bertrand , Vincent Marie , Nizon Mathilde , Mercier Sandra , Bonneau Dominique , Colin Estelle , Ziegler Alban , Audebert-Bellanger Séverine , Stoeva Radka , Demurger Florence , Thevenon Julien , Francannet Christine , Troude Baptiste , Perthus Isabelle , Haye Damien , Collignon Patrick , Gilbert-Dussardier Brigitte , Bilan Frédéric , Egloff Mattieu , Le Guyader Gwenaël , Letard Pascaline , Sarrazin Elisabeth , Giguet-Valard Anna-Gaëlle , Damaj Léna , Fradin Mélanie , Lavillaureix Alinoe , Jean-Marçais Nolwenn , Morel Godelieve , Quelin Chloé , Naudion Sophie , Legendre Marine , Van-Gils Julien , Rooryck-Thambo Caroline , Boute Odile , Dieux Anne , Vincent-Delorme Catherine , Ghoumid Jamal , Vanlerberghe Clémence , Caumes Roseline , Colson Cindy , Marsili Luisa , Wyrebski Antoine , Bellengier Laurence , Houdayer Françoise , Putoux Audrey , Busa Tiffany , Riccardi Florence , Missirian Chantal , Blanchet Patricia , Coubes Christine , Haquet Emmanuelle , Pinson Lucile , Puechberty Jacques , Wells Constance , Capri Yline , Perrin Laurence , Passemard Sandrine , Ruand Lyse , Nambot Sophie , Delanne Julian , Moutton Sébastien , Sorlin Arthur , Lehalle Daphné , Garde Aurore , Jannot Anne-Sophie , Binquet Christine , Sandrin Arnaud , Verloes Alain , Faivre Laurence 
Published: August 2021

Abstract
Background
In France, the Ministry of Health has implemented a comprehensive program for rare diseases (RD) that includes an epidemiological program as well as the establishment of expert centers for the clinical care of patients with RD. Since 2007, most of these centers have entered the data for patients with developmental disorders into the CEMARA population-based registry, a national online data repository for all rare diseases. Through the CEMARA web portal, descriptive demographic data, clinical data, and the chronology of medical follow-up can be obtained for each center. We address the interest and ongoing challenges of this national data collection system 10 years after its implementation.

Methods
Since 2007, clinicians and researchers have reported the “minimum dataset (MDS)” for each patient presenting to their expert center. We retrospectively analyzed administrative data, demographic data, care organization and diagnoses.

Results
Over 10 years, 228,243 RD patients (including healthy carriers and family members for whom experts denied any suspicion of RD) have visited an expert center. Among them, 167,361 were patients affected by a RD (median age 11 years, 54% children, 46% adults, with a balanced sex ratio), and 60,882 were unaffected relatives (median age 37 years). The majority of patients (87%) were seen no more than once a year, and 52% of visits were for a diagnostic procedure. Among the 2,869 recorded rare disorders, 1,907 (66.5%) were recorded in less than 10 patients, 802 (28%) in 10 to 100 patients, 149 (5.2%) in 100 to 1,000 patients, and 11 (0.4%) in > 1,000 patients. Overall, 45.6% of individuals had no diagnosis and 6.7% had an uncertain diagnosis. Children were mainly referred by their pediatrician (46%; n = 55,755 among the 121,136 total children referrals) and adults by a medical specialist (34%; n = 14,053 among the 41,564 total adult referrals). Given the geographical coverage of the centers, the median distance from the patient’s home was 25.1 km (IQR = 6.3 km-64.2 km).

Conclusions
CEMARA provides unprecedented support for epidemiological, clinical and therapeutic studies in the field of RD. Researchers can benefit from the national scope of CEMARA data, but also focus on specific diseases or patient subgroups. While this endeavor has been a major collective effort among French RD experts to gather large-scale data into a single database, it provides tremendous potential to improve patient care.