Diagnostic pathways in developmental disorders: a decade-apart comparison of two multicenter cohorts (2012–2022)

Abstract As part of the third French National Plan for Rare Diseases, the AnDDI-Rares network initiated a nationwide study in 2019 to assess how diagnostic practices for developmental anomalies have evolved over the last decade (2012–2022), in the context of the implementation of genome sequencing (GS) capabilities via the France Genomic Medicine Plan. We analyzed diagnostic rates in 34 French centers for developmental diseases, comparing a randomly selected week in 2012 with one in 2022. Secondary outcomes were diagnostic delays and GS efficiency. A total of 430 patients were identified in 2012 and 551 in 2022, a 28% increase in activity. The overall diagnostic yield rose from 16% in 2012 to 27% in 2022 ( p < 0.001), in parallel with the increased use of next-generation sequencing (NGS) approaches, and the shift from targeted gene panels toward GS. Among previously undiagnosed patients from the 2012 cohort who pursued further investigations, NGS enabled additional diagnoses with GS showing a high diagnostic yield (42%) in individuals with longstanding diagnostic odysseys. Significant heterogeneity in strategies persisted, highlighting the impact of, and unequal access to GS across centers. These results highlight advancements in diagnostic practices and the pivotal role of Next-Generation Sequencing. Nonetheless, unequal access, attrition, and limited uptake of renewed investigations reveal persistent barriers. Continuous patient engagement and coordinated efforts are required to promote GS-first approaches and ensure equitable access across the healthcare system.

Authors

Institutions

Publication Details

Journal
European Journal of Human Genetics
Published
2026-10-06
DOI
https://doi.org/10.1038/s41431-026-02242-3
Primary Topic
Genomics and Rare Diseases
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Diagnostic pathways in developmental disorders: a decade-apart comparison of two multicenter cohorts (2012–2022)

Bénédicte Deemer, Marie‐Line Jacquemont, Caroline Racine, Rodolphe Dard et al.
European Journal of Human Genetics
Genomics and Rare Diseases
article

Diagnostic pathways in developmental disorders: a decade-apart comparison of two multicenter cohorts (2012–2022)

Bénédicte Deemer, Marie‐Line Jacquemont, Caroline Racine, Rodolphe Dard, Juliette Piard, Maude Grelet, Christel Thauvin‐Robinet, Céline Poirsier, Frédéric Bilan, Florence Démurger, Gwenaël Le Guyader, Renaud L. Touraine, Matthieu Egloff, Laurence Olivier Faivre, Laurent Demougeot, Séverine Audebert‐Bellanger, Jeanne Amiel, Laëtitia Lambert, Estelle Colin, Sabine Sigaudy, Julien Maraval, Mathilde Renaud, Marilyn Lackmy, Christine Binquet, Élise Schaefer, Pauline Monin, Cindy Colson, Marta Spodenkiewicz, Camille Cenni, Florence Jobic, Philippe Khau Van Kien, Annick Toutain, Andrée Delahaye‐Duriez, Pierre Blanc, Radka Stoeva, Fanny Laffargue, Dominique Bonneau, David Geneviève, Sylvie Odent, Didier Lacombe, Yline Capri, Anne‐Marie Guerrot, Mathieu Milh, Aline Vincent‐Devulder, Antoine Journé, Hortense Thomas, Sylvie Odent, Bertrand Isidor, Odile Boute, Anne-Sophie Briffaut, Aurore Pélissier, Marie-Laure Asensio, Isabelle Marey, Christine Francannet, Olivier Patat, Niki Sabour, Philippe Khau Van Kien, André Delahaye-Duriez, Céline Poitevin, Cyril Mignot, Céline Dampfhoffer, Christine Vinciguera, The AnDDI-Rares Diagnostic Observatory Network
article en

Abstract

Abstract As part of the third French National Plan for Rare Diseases, the AnDDI-Rares network initiated a nationwide study in 2019 to assess how diagnostic practices for developmental anomalies have evolved over the last decade (2012–2022), in the context of the implementation of genome sequencing (GS) capabilities via the France Genomic Medicine Plan. We analyzed diagnostic rates in 34 French centers for developmental diseases, comparing a randomly selected week in 2012 with one in 2022. Secondary outcomes were diagnostic delays and GS efficiency. A total of 430 patients were identified in 2012 and 551 in 2022, a 28% increase in activity. The overall diagnostic yield rose from 16% in 2012 to 27% in 2022 ( p < 0.001), in parallel with the increased use of next-generation sequencing (NGS) approaches, and the shift from targeted gene panels toward GS. Among previously undiagnosed patients from the 2012 cohort who pursued further investigations, NGS enabled additional diagnoses with GS showing a high diagnostic yield (42%) in individuals with longstanding diagnostic odysseys. Significant heterogeneity in strategies persisted, highlighting the impact of, and unequal access to GS across centers. These results highlight advancements in diagnostic practices and the pivotal role of Next-Generation Sequencing. Nonetheless, unequal access, attrition, and limited uptake of renewed investigations reveal persistent barriers. Continuous patient engagement and coordinated efforts are required to promote GS-first approaches and ensure equitable access across the healthcare system.

European Journal of Human Genetics
Université Claude Bernard Lyon 1 (FR), Centre National de la Recherche Scientifique (FR), Inserm (FR), Université de Bourgogne (FR), Centre Hospitalier Universitaire de Grenoble (FR), Centre Hospitalier Universitaire de Lille (FR), Sorbonne Université (FR), Université Sorbonne Paris Nord (FR), Centre Hospitalier Universitaire de Tours (FR), Assistance Publique – Hôpitaux de Paris (FR), Centre Hospitalier Universitaire de Reims (FR), Normandie Université (FR), Centre Hospitalier Intercommunal de Poissy (FR), Laboratoire National de Référence (MA), Centre Hospitalier Universitaire de Caen Normandie (FR), CHU Dijon Bourgogne (FR), CIC Rennes (FR), Hôpitaux Universitaires Paris-Ouest (FR), Centre Hospitalier du Mans (FR), Institut de génétique et de développement de Rennes (FR), Centre Hospitalier Universitaire de Clermont-Ferrand (FR), Centre de recherche Translationnelle en Médecine moléculaire (FR), Centre Hospitalier Universitaire Pointe-à-Pitre (GP), Hôpitaux Universitaires de Strasbourg (FR), Université Bourgogne Europe (FR), Université de Rouen Normandie (FR), Université de Lorraine (FR), Université de Reims Champagne-Ardenne (FR), Université de Caen Normandie (FR)
Openalex Percentile: Top 13%
Genomics and Rare Diseases
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.