Evidence map›Paper›PMID 42016445›Full record

ArticleGenetics in medicine open2026

Telethon Undiagnosed Disease Program: Structured approach to solving rare childhood-onset genetic diseases.

Annalaura Torella, Manuela Morleo, Carmine Spampanato, Raffaele Castello, Mariateresa Zanobio, Giulio Piluso, Pasquale Di Letto, Maria Elena Onore, Sarah Iffat Rahman, Francesco Musacchia and 41 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genetics in medicine open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

51 authors.

Annalaura TorellaTelethon Institute of Genetics and Medicine, Pozzuoli, Italy.
Manuela MorleoTelethon Institute of Genetics and Medicine, Pozzuoli, Italy.
Carmine SpampanatoTelethon Institute of Genetics and Medicine, Pozzuoli, Italy.
Raffaele CastelloTelethon Institute of Genetics and Medicine, Pozzuoli, Italy.
Mariateresa ZanobioDepartment of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples, Italy.
Giulio PilusoDepartment of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples, Italy.
Pasquale Di LettoDepartment of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples, Italy.
Maria Elena OnoreDepartment of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples, Italy.
Sarah Iffat RahmanDepartment of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples, Italy.
Francesco MusacchiaTelethon Institute of Genetics and Medicine, Pozzuoli, Italy.
Michele PinelliDepartment of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
Giuseppina VitielloDepartment of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
Giulia De RisoDepartment of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
Angelo SelicorniDepartment of Pediatrics, ASST Lariana Sant'Anna Hospital, Como, Italy.
Milena MarianiDepartment of Pediatrics, ASST Lariana Sant'Anna Hospital, Como, Italy.
Cecilia DaolioPediatrics, IRCCS San Gerardo dei Tintori Foundation, Monza, Italy.
Valeria CapraMedical Genetics Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Marcello ScalaMedical Genetics Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Francesca NardecchiaUnit of Child Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
Serena GalosiUnit of Child Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
Mario MastrangeloDepartment of Women/Health and Urological Science, Sapienza, Università di Roma.
Filippo MantiUnit of Child Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
Donatella MilaniFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
Corrado RomanoResearch Unit of Rare Diseases and Neurodevelopmental Disorders Oasi Research Institute-IRCCS, Troina, Italy.
Donatella GrecoResearch Unit of Rare Diseases and Neurodevelopmental Disorders Oasi Research Institute-IRCCS, Troina, Italy.
Claudia CiaccioDepartment of Pediatric Neurology, Istituto Neurologico Carlo Besta, Milan, Italy.
Stefano D'ArrigoDepartment of Pediatric Neurology, Istituto Neurologico Carlo Besta, Milan, Italy.
Arianna De LaurentiisDepartment of Pediatric Neurology, Istituto Neurologico Carlo Besta, Milan, Italy.
Antonietta CoppolaDepartment of Neuroscience, Reproductive and Odontostomatological Sciences, Epilepsy Center, University of Naples Federico II, Naples, Italy.
Marcella ZollinoUnit of Medical Genetics, Policlinico Universitario "A. Gemelli Foundation IRCCS," Rome, Italy.
Domizia PasquettiUnit of Medical Genetics, Policlinico Universitario "A. Gemelli Foundation IRCCS," Rome, Italy.
Federica Francesca L'ErarioUnit of Medical Genetics, Policlinico Universitario "A. Gemelli Foundation IRCCS," Rome, Italy.
Albina TummoloDepartment of Metabolic Diseases, Clinical Genetics and Diabetology, Giovanni XXIII Children Hospital, Azienda Ospedaliero-Universitaria Consorziale, Bari, Italy.
Claudia SantoroDepartment of Women, Child, General and Specialized Surgery, University of Campania "Luigi Vanvitelli" Naples, Italy.
Livia GaravelliMedical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
Carla MariniChild Neurology and Psychiatric Unit, Salesi Children Hospital, Ancona, Italy.
Stefania BigoniMedical Genetics Unit, Department of Mother and Child, University Hospital of Ferrara, Ferrara, Italy.
Alfonsina TirozziClinical Genetic Unit, Santobono-Pausilipon Children's Hospital, AORN, Naples, Italy.
Viviana CetrangoloTelethon Institute of Genetics and Medicine, Pozzuoli, Italy.
Giancarlo ParentiTelethon Institute of Genetics and Medicine, Pozzuoli, Italy.
Diego Di BernardoTelethon Institute of Genetics and Medicine, Pozzuoli, Italy.
Angela PeronDivision of Medical Genetics, Meyer Children's Hospital IRCCS, Florence, Italy.
Silvia MaitzMedical Genetics Service, Oncology Department of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano, Switzerland.
Andrea AccogliDivision of Medical Genetics, Department of Medicine, and Department of Human Genetics, McGill University Health Center, Montreal, QC, Canada.
Gerarda CappuccioDepartment of Translational Medical Sciences, Pediatrics Section, Federico II University of Naples, Naples, Italy.
Sandro BanfiTelethon Institute of Genetics and Medicine, Pozzuoli, Italy.
Giorgio CasariVita-Salute San Raffaele University, Milan, Italy.
Andrea BallabioTelethon Institute of Genetics and Medicine, Pozzuoli, Italy.
Nicola Brunetti-PierriTelethon Institute of Genetics and Medicine, Pozzuoli, Italy.
Vincenzo NigroTelethon Institute of Genetics and Medicine, Pozzuoli, Italy.
Telethon Undiagnosed Disease Study group

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Purpose: Many children with severe genetic disorders remain undiagnosed despite advanced genomic technologies. Early diagnosis is vital for prognosis, genetic counseling, and targeted treatment development. This study aims to increase diagnostic rates in complex pediatric cases and foster research into disease mechanisms. Methods: Launched in 2016, the Telethon Undiagnosed Diseases Program provides a structured, multicenter approach to rare disease diagnosis. Standardized case submission criteria ensured consistent clinical data collection. Children with severe, multisystemic disorders and prior negative genetic tests were eligible. After case approval, trio-based exome sequencing was performed, with regular reanalysis for unsolved cases until December 2024. Results: Between June 2016 and December 2023, 1338 cases were submitted by 60 clinicians from 22 Italian centers; 1019 were accepted. A definitive genetic diagnosis was achieved in 49% of cases, implicating 330 genes. Most pathogenic variants (70.2%) were de novo, reflecting demographic trends, such as delayed parenthood. The remainder included autosomal recessive or X-linked variants, with homozygosity observed in 9% of patients. Conclusion: The Telethon Undiagnosed Diseases Program significantly shortened the average diagnostic odyssey of ∼8 years. Children born after 2016 benefited from faster diagnoses. This initiative offers a scalable, cost-effective model for improving diagnosis, guiding treatment, and supporting therapeutic innovation in rare pediatric diseases.

Indexed as

Exome sequencingGenetic diagnosisPediatric genomicsRare diseasesUndiagnosed Diseases Program

Identifiers

PMID42016445
PMCPMC13094511

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.