Undiagnosed Diseases Network Sweden – UDN Sweden

The Undiagnosed Diseases Network Sweden (UDN Sweden), which is part of the GMS Rare Diseases programme, is a multicentre study that aims to implement whole genome sequencing for children across the country in a fair and equitable manner. This initiative is focused on children with undiagnosed rare syndromes that involve malformations and/or intellectual disabilities. The research network is part of the Undiagnosed Diseases Network International (UDNI), an international expert network founded in 2014 to provide diagnoses to patients, implement diagnostic tools, and promote research into new diseases and their mechanisms.

UDN Sweden is a multidisciplinary network consisting of health care professionals from different areas of expertise, including clinical geneticists, paediatricians, molecular biologists, clinical laboratory scientists, nurses, bioinformaticians and genetic counsellors, from the country’s university hospitals. The team consists of diagnostic experts with extensive experience in clinical and genetic characterization of patients with intellectual disabilities and/or malformations, symptoms that are part of the European Reference Network ERN-ITHACAs (European Reference Network for Rare Malformation Syndromes, Intellectual and Other Neurodevelopmental Disorders) focus areas.

In 2023, phase 1 of the project was carried out, and phase 2 has been started in 2024. UDN Sweden is supported by the Swedish Ministry of Social Affairs.

Whole Genome Sequencing plays a crucial role in diagnosis

A diagnosis for suspected rare diseases is of direct importance for care, management, family planning, and support measures for the individual and the entire family. Thanks to research and modern genetic technology, today, 40% of all individuals examined with whole genome sequencing can receive a confirmed causative diagnosis.

The development of new methods for genetic diagnostics has been rapid in recent years. These new techniques have increased the possibility of making the correct diagnosis, assessing whether a disease is hereditary, and in some cases, providing guidance for choosing targeted treatment. However, much is still unknown about how different genetic variants can lead to diseases.

Sweden has been at the forefront in using whole genome sequencing for diagnosing individuals with suspected rare diseases. Thanks to the work within GMS and SciLifeLab Clinical Genomics, Sweden is at the forefront of genetic diagnostics globally. Currently, however, only a portion of individuals with rare diseases involving malformations and/or intellectual disabilities are offered whole genome sequencing diagnostics. There are also significant disparities in the country regarding who is offered genetic investigation.

The purpose of the project is to prepare healthcare to meet the growing demand for whole genome sequencing. It also aims to investigate whether more patients can be diagnosed by combining various methods of modern genetic technology. The project also seeks to improve clinical characterization and harmonize investigations to accelerate the implementation of equal access to precision diagnostics for patients with rare syndromes, as well as evaluate the process surrounding genetic testing, genetic counselling, and the significance of a diagnosis as experienced by participants.

About the study

Research participation

The research study aims to find causes in individuals with malformations and/or intellectual disabilities and study these conditions. The inclusion criteria for the study are children with a rare and unclear diagnosis of malformations and/or IF, where the parents have consented to their participation in all aspects of the study. The recruitment of research participants is facilitated by patient organisations such as the Wilhelm Foundation and Anonymous, as well as by treating physicians and the regional department of clinical genetics.

How the study works

First, a clinical investigation is conducted to try to establish a diagnosis. The research project begins after the clinical analyses have been completed without providing a definitive answer. At this point, a more detailed characterization of the child’s symptoms is carried out, along with further analyses using modern genetic technology to identify known and new disease genes or mechanisms that have not been described before. Parents will also fill out questionnaires and answer questions regarding the diagnostic process and the significance of a diagnosis.

Simultaneous analysis of DNA samples from close relatives often facilitates the analysis and increases the possibility of establishing a diagnosis. If the genetic analysis shows a variant that is difficult to interpret, further analysis may be required to clarify if there is a connection to the diagnosis. Sometimes, genetic analyses cannot directly explain why the disease occurred, and other methods or studies of different tissues may be needed to evaluate the genetic results.

Participation in the study has the potential to result in a diagnosis. An accurate genetic diagnosis can facilitate prediction of disease progression, inform treatment choices and surveillance programmes, and enable risk assessment for other family members. With a genetic diagnosis, prenatal testing for the disease is also possible. The results may also lead to an increased understanding of the origin and development of diseases.

Analysis results

Once the analyses are completed, the referring physician who ordered the analysis will communicate the results to the participants, a process that will also be formally documented in the individual’s medical record. It can sometimes take many years before another individual with the same genetic variant is identified or new knowledge emerges that impacts the ability to interpret the analysis. If new information becomes available or a new individual with the same genetic variant is found, the research participants will be re-contacted. The response time for the initial part of the analyses in the project may range from about 6 months to 1 year.

Study responsibility and contact information

You may contact the project via email at gms.rd.karolinska@regionstockholm.se for further questions. The undersigned serve as the local contact for the study and will be pleased to offer additional information as required.
Ann Nordgren, professor, senior physician, clinical geneticist, leader of UDN Sweden
Angélica M Delgado-Vega, postdoc, specialist in clinical genetics, clinical coordinator
Fulya Taylan, docent, research specialist, laboratory coordinator
Katja Ekholm, doctoral student, nurse, genetic counsellor, psychosocial study coordinator
Eva Ekblom, administrative coordinator
Britt-Marie Anderlid, docent, senior physician, peadiatric neurologist, clinical geneticist