Developmental Delay (Disorder), Dysmorphia, Intellectual Developmental Disorder, Malformations
Conditions
Keywords
Whole Genome Sequencing, Whole Exome Sequencing, Rare Disease
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.
Interventions
DIAGNOSTIC_TESTWhole exome sequencing
Whole exome sequencing using Illumina short read sequencing
DIAGNOSTIC_TESTWhole genome Sequencing
Whole genome sequencing using Illumina short read sequencing
Sponsors
Universitair Ziekenhuis Brussel
Erasme University Hospital
University Ghent
Universiteit Antwerpen
Université de Liège
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Institut de Pathologie et de Génétique Charleroi
Universitaire Ziekenhuizen KU Leuven
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Whole genome sequencing (WGS) performance compared to Whole exome sequencing (WES) performance | 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. |
Countries
Belgium
Outcome results
None listed