Undiagnosed diseases Programme

Obtaining a diagnosis is crucial for those affected by a genetic disease: it means giving a name to their disease, offering the possibility of accessing the available information, either through the international scientific literature or through the experience of other families, and to improve the care and management of both everyday life and emergency situations.

Diagnosing a disease at the molecular level also allows obtaining biological and genetic information, paving the way to targeted genetic counselling, both concerning the possibility of a recurrence of the disease in any new children, and in brothers/sisters or other relatives.

Despite the numerous efforts of the medical and scientific community and advances in DNA analysis, there are still thousands of very rare genetic diseases with unknown causes or that remain undiagnosed.

In order to provide an answer to undiagnosed patients, mainly in childhood, and to begin to fill this need, the Telethon Foundation has devised a unique programme in Italy coordinated by the Telethon Institute of Genetics and Medicine (Tigem) in Pozzuoli (NA) and launched in 2016: the Undiagnosed Diseases Programme (TUDP) of Fondazione Telethon.

As described in Genetics in Medicine OPEN (the journal of the American College of Medical Genetics and Genomics), in its first eight years (2016–2023) TUDP covered more than 1,300 pediatric cases evaluated at 22 specialist centers in Italy. 

The program achieved a definitive genetic diagnosis in 49% of enrolled children, a diagnostic yield that compares favourably with other undiagnosed disease initiatives worldwide. Pathogenic variants were identified across 330 genes, reflecting the wide genetic diversity of childhood-onset rare conditions. More than 70% of causative variants were de novo, arising spontaneously with no prior family history.

The TUDP Clinical Centre Network comprises an increasing number of clinical centres across Italy. Genetic analysis is carried out at Tigem laboratories and at the Azienda Ospedaliera Universitaria - Università degli Studi della Campania Luigi Vanvitelli on samples collected and sent to the laboratories by the clinical centres, upon informed consent of the patient or his/her family members.

The researchers of the undiagnosed diseases programme use cutting-edge technologies such as next-generation sequencing of DNA and RNA (Next Generation Sequencing, or NGS), i.e. whole genome sequencing (WGS) or transcriptome sequencing (RNA-seq). Reanalysis of unsolved cases is performed with advanced bioinformatics tools, or following the availability of more advanced techniques or new genetic and clinical information, also thanks to comparison with data in other international databases.

As of 2024, the TUDP Network involves 22 Italian paediatric hospitals:

For any inquiries about the TUDP, send an email to: telethonscience@telethon.it