Improving diagnosis for rare diseases: the experience of the Italian undiagnosed Rare diseases network

Italian Journal of Pediatrics

Giovanna Floridia¹  Giuseppe Novelli²  Federica Sangiuolo³  Savino Sciascia⁴  Elisa Menegatti⁴  Dario Roccatello⁴  Simone Baldovino⁴  Agata Polizzi⁵  Alessandra Ferlini⁶  Marcella Neri⁶  Francesco Brancati⁷  Paraskevas Iatropoulos⁸  Giuseppe Remuzzi⁸  Erica Daina⁸  Domenica Taruscio⁹  Marco Salvatore⁹  Maria Chiara De Stefano^1,10  Rosalia Maria Da Riol^1,11  Bruno Bembi^1,11 

[1] Bioethics Unit, Istituto Superiore di Sanità, Rome, Italy;Department of Biomedicine and Prevention, University of Tor Vergata and University Hospital Tor Vergata, Unit of Medical Genetics Rome & IRCCS Neuromed, Pozzilli, Italy;Department of Biomedicine and Prevention, University of Tor Vergata and University Hospital Tor Vergata, Unit of Medical Genetics, Rome, Italy;Department of Clinical and Biological Sciences, University of Turin and S. Giovanni Bosco Hospital, Centre of Research of Immunopathology and Rare Diseases – Regional Coordinating Centre of the National Network for Rare Diseases, Turin, Italy;Department of Educational Science, University of Catania, Catania, Italy;Department of Experimental and Diagnostic Medicine, University of Ferrara, Ferrara, Italy;Department of Life, Health and Environmental Sciences, Unit of Medical Genetics University of L’Aquila, L’Aquila, Italy;IRCCS Mario Negri Pharmacological Research Institute, Regional Coordinating Centre of the National Network for Rare Diseases, Clinical Research Centre for Rare Diseases “Aldo e Cele Daccò”, Ranica, Bergamo, Italy;National Centre for Rare Diseases, Undiagnosed Rare Diseases Interdepartmental Unit, Istituto Superiore di Sanità, Rome, Italy;National Transplantation Centre, Istituto Superiore di Sanità, Rome, Italy;S.O.C. Regional Coordinating Centre of the National Network for Rare Diseases, S. Maria della Misericordia Hospital, Udine, Italy;

关键词: Undiagnosed;    Rare diseases;    Omics;    Ontology;    Diagnosis;   

DOI  :  10.1186/s13052-020-00883-8

来源: Springer

【 摘 要 】

BackgroundFor a number of persons with rare diseases (RDs) a definite diagnosis remains undiscovered with relevant physical, psychological and social consequences. Undiagnosed RDs (URDs) require other than specialised clinical centres, outstanding molecular investigations, common protocols and dedicated actions at national and international levels; thus, many “Undiagnosed RDs programs” have been gradually developed on the grounds of a well-structured multidisciplinary approach.MethodsThe Italian Undiagnosed Rare Diseases Network (IURDN) was established in 2016 to improve the level of diagnosis of persons with URD living in Italy. Six Italian Centres of Expertise represented the network. The National Centre for Rare Diseases at the Istituto Superiore di Sanità coordinates the whole project. The software PhenoTips was used to collect the information of the clinical cases.ResultsOne hundred and ten cases were analysed between March 2016 and June 2019. The age of onset of the diseases ranged from prenatal age to 51 years. Conditions were predominantly sporadic; almost all patients had multiple organs involvements. A total of 13/71 family cases were characterized by WES; in some families more than one individual was affected, so leading to 20/71 individuals investigated. Disease causing variants were identified in two cases and were associated to previously undescribed phenotypes. In 5 cases, new candidate genes were identified, although confirmatory tests are pending. In three families, investigations were not completed due to the scarce compliance of members and molecular investigations were temporary suspended. Finally, three cases (one familial) remain still unsolved. Twelve undiagnosed clinical cases were then selected to be shared at International level through PhenomeCentral in accordance to the UDNI statement.ConclusionsOur results showed a molecular diagnostic yield of 53,8%; this value is comparable to the diagnostic rates reported in other international studies. Cases collected were also pooled with those collected by UDNI International Network. This represents a unique example of global initiative aimed at sharing and validating knowledge and experience in this field. IURDN is a multidisciplinary and useful initiative linking National and International efforts aimed at making timely and appropriate diagnoses in RD patients who still do not have a confirmed diagnosis even after a long time.

【 授权许可】

CC BY