The Belgian Genome Resource to Resolve Rare Diseases

NCT07051213 | Completed

• 1 other identifier: S64603
• Study Type: interventional
• Target: 567
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Intellectual Developmental Disorder; Malformations; Dysmorphia; Developmental Delay (Disorder)

Keywords

Whole Genome Sequencing; Whole Exome Sequencing; Rare Disease

Outcome Measures

Primary Outcomes (1)

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

  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.

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

Study Arms (2)

Standard of Care including Whole Exome Sequencing

ACTIVE COMPARATOR

Standard of care consisting of a combination of a chromosomal microarray or shallow whole genome sequencing (standard of care copy number variant analysis in the concerned genetic center) with whole exome sequencing.

Diagnostic Test: Whole exome sequencing

Whole Genome Sequencing

EXPERIMENTAL

Whole genome sequencing (primary analysis using a similar pipeline as the one used for whole exome sequencing - re-analysis using Emedgene to detect potential repeat expansions, structural and/or intronic variants)

Diagnostic Test: Whole genome Sequencing

Interventions

Whole exome sequencing DIAGNOSTIC_TEST

Whole exome sequencing using Illumina short read sequencing

Standard of Care including Whole Exome Sequencing

Whole genome Sequencing DIAGNOSTIC_TEST

Whole genome sequencing using Illumina short read sequencing

Whole Genome Sequencing

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead
• Universitair Ziekenhuis Brussel: collaborator
• Erasme University Hospital: collaborator
• University Ghent: collaborator
• Universiteit Antwerpen: collaborator
• Université de Liège: collaborator
• Cliniques universitaires Saint-Luc- Université Catholique de Louvain: collaborator
• Institut de Pathologie et de Génétique Charleroi: collaborator

Study Sites (1)

KU Leuven

Leuven, Belgium

Location

MeSH Terms

Conditions

Intellectual Disability; Congenital Abnormalities; Developmental Disabilities; Rare Diseases

Interventions

Exome

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurodevelopmental Disorders; Mental Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Disease Attributes; Pathologic Processes

Intervention Hierarchy (Ancestors)

Genome; Genetic Structures; Genetic Phenomena

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2025
• First Posted: July 4, 2025
• Study Start: June 2, 2021
• Primary Completion: July 5, 2024
• Study Completion: January 31, 2025
• Last Updated: July 4, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share

Locations

BE (1)