Genetic Newborn Screening for Rare Diseases Within the Screen4Care Project
NCT Number: NCT06549218
Acronym: SCREEN4CARE
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Newborn Screening
Interventions: DIAGNOSTIC_TEST: newborn genetic screening and whole genome sequencing
Sponsor: University Hospital Freiburg
Collaborators: Innovative Medicines Initiative|Università degli Studi di Ferrara|Ospedale Pediatrico Bambin Gesù|University of Siena|Centre Hospitalier Universitaire Dijon|Real Genix|University Hospital Erlangen|University Hospital Goettingen|Centro Nacional de Análisis Genómico|Genoox
Sex: ALL
Age: CHILD
Enrollment: 20000
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: SCREENING
Start Date: 2024-09
Completion Date: 2025-12

Summary:
The main objective of the genetic newborn screening part of the Screen4Care-project is to shorten the path to rare disease diagnosis and to facilitate early intervention. Therefore, genetic newborn screening for currently treatable rare diseases (TREAT-panel approach) will be offered to families expecting a baby. Whole genome sequencing (WGS) will be offered as additional diagnostic approach to newborns participating in Screen4Care TREAT-panel approach, if they develop symptoms suggestive of a genetic disease.

To evaluate to what extend genetic newborn screening has an impact on participating infants and their families, a follow-up with standardised questionnaires will be performed for all participating families.

Primary Outcome Measures: TREAT-panel, • Percentage of eligible couples who will accept to participate to the genetic newborn screening, 1 year|TREAT-panel, • Percentage of infants in whom pathogenic or likely pathogenic variants that predict one of the target diseases will be identified, 1 year|Whole Genome Sequencing, • Percentage of symptomatic patients whom parents will accept to be enrolled in whole genome sequencing, 2 years|Whole Genome Sequencing, • Percentage of known disease genes where pathogenic variations will be identified by whole genome sequencing in enrolled patients, 2 years|Whole Genome Sequencing, • Percentage of infants where genetic diagnosis is achieved by whole genome sequencing, 2 years
Secondary Outcome Measures: TREAT-panel, • Clinical follow-up of infants with positive findings in gNBS, 1 year|TREAT-panel, • Impact of genetic NBS on parents as assessed by standardized questionnaires, 1 year|TREAT-panel, • Carrier frequency of recessive diseases (both autosomal and X-linked) and percentage of variants of unknown significance identified through gNBS., 1 year|TREAT-panel, • Percentage of study participants who develop symptoms of a genetic disease after negative newborn screening and are diagnosed by whole genome sequencing (aggregated data analysis, not reported to participants), 1 year|TREAT-panel, • Impact of positive findings in gNBS on the health care and outcome of study participants, 1 year|Whole Genome Sequencing, • Percentage of novel disease genes (phenotype discovery) where pathogenic variations will be identified by Whole Genome Sequencing in enrolled patients, 2 years|Whole Genome Sequencing, • Number of VUS identified in known disease genes, 2 years|Whole Genome Sequencing, • Number of VUS identified in novel disease genes/phenotypes, 2 years|Whole Genome Sequencing, • Diagnostic yield of Whole Genome Sequencing compared to genetic newborn screening, 2 years