The Belgian Genome Resource to Resolve Rare Diseases

Whole-exome (WES) or whole-genome sequencing (WGS) are recommended as first- or second-tier molecular tests for patients with developmental disorders (DD), but the clinical utility of WGS continues to be debated. This prospective randomized trial involving all Belgian Human Genetics centers compares the standard of care (SoC) - combining WES and microarray or shallow WGS - with WGS for 567 individuals with unexplained DD. The aim of the project is to pave the way towards diagnostic implementation of WGS for rare DD in Belgium. To reach this aim, (1) technical validation is performed at different genetic centres in Belgium, (2) clinical utility of WGS is explored and (3) the health economic impact is mapped.

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Key information

Conditions

Intellectual Developmental Disorder Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Developmental Delay (Disorder) Developmental Disabilities Disease Attributes Dysmorphia Intellectual Disability Malformations Mental Disorders Nervous System Diseases Neurobehavioral Manifestations Neurodevelopmental Disorders Neurologic Manifestations Pathologic Processes Pathological Conditions, Signs and Symptoms Rare Diseases Signs and Symptoms

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

KU Leuven

Leuven, Belgium

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Intellectual disability/Developmental delay (moderate to profound)
Intellectual disability/Developmental delay (mild to moderate) AND family recurrence AND normal parents
Intellectual disability/Developmental delay (mild to moderate) AND dysmorphism (≥3 well documented minor signs)
One major malformation AND dysmorphism (≥3 well documented minor signs)
Multiple major malformations in 2 or more different organ systems.

Exclusion criteria

Suspicion of an acquired cause, e.g. congenital infection and prenatal toxic exposure
Prior next-generation sequencing of a gene panel targeting multiple conditions or prior exome analyses

Treatment and study plan

Whole Exome Sequencing

Diagnostic Test

Whole exome sequencing using Illumina short read sequencing

Whole genome sequencing

Diagnostic Test

Whole genome sequencing using Illumina short read sequencing

Primary outcomes

Whole genome sequencing (WGS) performance compared to Whole exome sequencing (WES) performance

Time frame: From enrollment to reporting the results of the analysis : target turn around time of 6 months

The primary outcome measure is to determine whether whole genome sequencing is able to improve the diagnostic yield of next-generation sequencing for developmental disorders.

Sponsors and collaborators

Lead sponsor

Universitaire Ziekenhuizen KU Leuven

Other

Collaborators

Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Erasme University Hospital
Institut de Pathologie et de Génétique Charleroi
Universitair Ziekenhuis Brussel
Universiteit Antwerpen
University Ghent
Université de Liège

Registry information

Acronym: BeSolveRD

Important dates

Study start: 2021
Primary completion: 2024
Study completion: 2025
First posted: Jul 4, 2025
Registry last updated: Jul 4, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed