Argo Delphi consensus statement on red flags and clinical gateways towards rare disease diagnosis

People living with a rare disease can wait months to years for a confirmed diagnosis after symptom onset, mainly due to low prevalence, lack of awareness of primary healthcare professionals, heterogeneous clinical presentation and/or peculiar inheritance patterns. This consensus paper aims to establish a set of guidelines to assist healthcare professionals-also without a specialized expertise in rare diseases-in optimizing the diagnostic pathway for these conditions. During Phase 1 of a real-time Delphi study, ten experts defined 26 statements addressing the identification of clinical features ("red flags", domain 1) and non-clinical tools/conditions ("clinical gateways", domain 2) that could trigger/support the diagnostic suspect of a rare disease. During Phase 2, the survey was extended to a multidisciplinary panel of 55 experts to reach a consensus on statements. Consensus was reached on 22 out of 26 statements across the two domains. Family history, clusters of birth defects, unusual presentations of common disease, neurodevelopmental delays or decline, and severe pathology emerged as key indicators to improve the identification and referral of cases of rare disease and should be integrated into primary care practices. Education, increased awareness in the community and use of technology are possible gateways to facilitate early diagnosis in rare disease.

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Publication Details

Journal
Scientific Reports
Published
2025-11-11
DOI
https://doi.org/10.1038/s41598-025-23081-0
Citations
2
Primary Topic
Genomics and Rare Diseases
Type
article
Field-Weighted Citation Impact
3.63
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article

Argo Delphi consensus statement on red flags and clinical gateways towards rare disease diagnosis

Paolo Calabrò, Fabio Tedone, Loreto Gesualdo, Giancarlo Parenti et al.
2 citations
Scientific Reports
Genomics and Rare Diseases
3.63
article

Argo Delphi consensus statement on red flags and clinical gateways towards rare disease diagnosis

Paolo Calabrò, Fabio Tedone, Loreto Gesualdo, Giancarlo Parenti, Anna Pichiecchio, Davide Cafiero, Tiziana Corsetti, Andrea Fiorillo, G. Annichiarico, Annalisa Scopinaro, Marta Mosca, Simone Baldovino, Fabio De Iaco, Giada Tortora, Lorenzo Rizzo, Angelo Ravelli, Chiara De Stasio, Antonio Varone, Francesco Benedicenti, Alessandra Fabi, Erica Daina, Marco Ardigò, Martina Caiazza, Giulia Motola, Massimo Triggiani, Giuseppe Limongelli, Mauro Cancian, Stefano Bianchi, Margherita Ruoppolo, Anna Fusco, Paola Facchin, Iris Scala, Luca Sangiorgi, Amalia Forte, Cristina Scaletti, Roberto Tozzi, Lorenzo Maggi, Maria Piccione, Letterio S. Politi, Silvia Di Michele, Patrizia Suppressa, Anna Annunziata, Roberto Poscia, António Toscano, Cecilia Berni, Claudia Sgattoni, Alessandro Broccoli, Raffaele Scarpa, Rosa Grazia Bellomo, Gaetano Piccinocchi, Maurizio Scarpa, Simona Sica, Salvatore Savasta, Paolo A. Ascierto, Leandro Pecchia, Dario Roccatello, Maria Giuliano, Elena Rossi, Maria Galdo, Francesca Simonelli, Barbara Morgillo, Roberta Veneziano, Elisa Rozzi
article en
2 citations

Abstract

People living with a rare disease can wait months to years for a confirmed diagnosis after symptom onset, mainly due to low prevalence, lack of awareness of primary healthcare professionals, heterogeneous clinical presentation and/or peculiar inheritance patterns. This consensus paper aims to establish a set of guidelines to assist healthcare professionals-also without a specialized expertise in rare diseases-in optimizing the diagnostic pathway for these conditions. During Phase 1 of a real-time Delphi study, ten experts defined 26 statements addressing the identification of clinical features ("red flags", domain 1) and non-clinical tools/conditions ("clinical gateways", domain 2) that could trigger/support the diagnostic suspect of a rare disease. During Phase 2, the survey was extended to a multidisciplinary panel of 55 experts to reach a consensus on statements. Consensus was reached on 22 out of 26 statements across the two domains. Family history, clusters of birth defects, unusual presentations of common disease, neurodevelopmental delays or decline, and severe pathology emerged as key indicators to improve the identification and referral of cases of rare disease and should be integrated into primary care practices. Education, increased awareness in the community and use of technology are possible gateways to facilitate early diagnosis in rare disease.

Scientific ReportsVol. 15(1)
Università Cattolica del Sacro Cuore (IT), University of Pisa (IT), University of Messina (IT), Marche Polytechnic University (IT), University of Salerno (IT), Humanitas University (IT), University of Padua (IT), Università Campus Bio-Medico (IT), University of Cagliari (IT), Mario Negri Institute for Pharmacological Research (IT), University of Campania "Luigi Vanvitelli" (IT), University of Basilicata (IT), University of Pavia (IT), Policlinico Umberto I (IT), Regione Campania (IT), Istituto Giannina Gaslini (IT), Agostino Gemelli University Polyclinic (IT), Foundation Center (US), Ospedale di Bolzano (IT), Società Italiana di Cardiologia (IT), Fondazione Istituto Neurologico Nazionale Casimiro Mondino (IT), Azienda Unità Sanitaria Locale di Ferrara (IT), Urology Foundation (GB), Ospedale di Santo Spirito (IT), Azienda Ospedaliero Universitaria Ospedali Riuniti (IT), Department of Health (ES), Agenzia Regionale Sanitaria della Puglia (IT), Azienda Ospedaliero-Universitaria Careggi (IT), Federico II University Hospital (IT), Istituto di Ematologia di Bologna (IT), Agenzia Regionale Prevenzione e Ambiente della Regione Emilia-Romagna (IT), Federazione Medico Sportiva Italiana (IT), Azienda USL di Bologna (IT), Ospedale San Giovanni Bosco (IT), Istituto Ortopedico Rizzoli (IT), New York University Florence (IT), Bambino Gesù Children's Hospital (IT), Santobono Children's Hospital (IT), Ospedale Microcitemico (IT), University of Campania "Luigi Vanvitelli" (IT), CEINGE Biotecnologie Avanzate Franco Salvatore (Italy) (IT), Agenzia Regionale per la Protezione dell'ambiente ligure (IT), Accademia di Belle Arti di Catanzaro (IT), Società Italiana di Medicina Generale (IT), University of Palermo (AR), Ospedale Monaldi (IT), Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" (IT), Ospedale Maria Vittoria (IT), Azienda Ospedale - Università Padova (IT), Ospedale San Giuseppe (IT), Ospedale di Livorno (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Agenzia Regionale di Sanità della Toscana (IT), IRCCS Humanitas Research Hospital (IT), Fondazione IRCCS Istituto Neurologico Carlo Besta (IT), Regione Toscana, University of Florence (IT), University of Turin (IT), University of Bari Aldo Moro (IT), University of Naples Federico II (IT), University of Genoa (IT), University of Palermo (IT), University of Bologna (IT)
Openalex Percentile: Top 6%
Genomics and Rare Diseases
3.63
DOIOpen Access PDFOpenAlex
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