Genetic Newborn Screening for Rare Diseases Within the Screen4Care Project: the French Participation (S4C France)

Newborn screening (NBS) programs are established to screen infants shortly after birth for conditions that are treatable, but not always clinically evident in the newborn period. Traditionally metabolic markers in dried blood spots (DBS) are used to diagnose these diseases. NBS detects diseases for which early diagnosis and treatment reduce long-term complications and mortality. The screening programs vary widely across Europe: Italy currently screens for 48 diseases, whereas Germany screens for 19 diseases and France screens for 14.

Through advances of genetic testing technologies, it is nowadays also possible to use DNA sequencing from DBS to test for genetic diseases. In parallel, the number of diseases, for which treatments are available are constantly increasing.

This study aims to explore the use of more extensive genetic testing by panel-based next generation sequencing to screen newborns for treatable genetic diseases. Genetic newborn screening (gNBS) is one of the pillars and the "core" of WP3 of S4C European Innovative Medicines Innitiative (IMI).

project; indeed, this work package (WP3) aims to explore the use of gNBS in newborns as a gateway to shorten the diagnostic path and offer the opportunity for early treatment. gNBS will adopt different strategies interrogating currently treatable rare diseases (RDs) (TREAT-panel-approach) (Step1). The TREAT-panel will include 245 disease genes that are related to treatable genetic disorders, prioritising those with early onset and where natural history key elements are known.

Genome sequencing (GS) will be offered to symptomatic patients to identify known gNBS-escaped RDs and novel genes/phenotypes (Step 2). More rarely, it could identify a candidate gene not yet known in human pathology.

Study Overview

• Status: Recruiting
• Conditions: Genetic Predisposition to Disease
• Intervention / Treatment: Diagnostic test: DBS card; Biological: Blood samples

• Study Type: Observational
• Enrollment (Estimated): 1060

Contacts and Locations

• Study Contact: Name: Laurence OLIVIER-FAIVRE; Phone Number: +33 0380295313; Email: laurence.faivre@chu-dijon.fr

Study Locations

• France
  • Dijon, France, 21000
    • Recruiting
    • Chu Dijon Bourgogne
    • Contact: Laurence OLIVIER-FAIVRE; Phone Number: +33 0380295313; Email: laurence.faivre@chu-dijon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

If possible, dedicated information in the third trimester at the visit with the anaesthesiologists to at least one parent by a trained clinical study assistant, a midwife or a genetic counsellor, with the supervision of the genetic PI of the site.

Each participant of step 1 will be informed to recontact the S4C team if their infant develops clinical symptoms

Description

Inclusion Criteria:

For step 1

• Newborns less than 28 days, born in the maternity of Dijon University Hospital
• Informed consent signed by both parents/legal guardian/minor parents with parental authority over their child to participate in the present S4C study
• For the exploratory interviews, voluntary parents to participate

For step 2

• Early symptoms (within 24 months of life) suggestive of a rare genetic disease in infants resulted negative at the TREAT-panel gNBS
• Informed consent signed by both parents to participate in GS study

Exclusion Criteria:

Both steps

• Parents subject to a measure of legal protection (guardianship, tutorship)
• Parents subject to a court order
• Parents incapable of expressing consent
• Parents who is not affiliated with the national health insurance system

For step 1 - Any newborn in which clinical considerations preclude drawing 1.0 ml of blood for the additional blotting paper

For step 2

- Infants not screened by TREAT-panel gNBS

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
participants; 1000 newborns are expected to take part in step 1	Diagnostic test: DBS card; Collection of a second DBS card
tios; infants resulted negative at the TREAT-panel gNBS at the step 1 and their parents	Biological: Blood samples; Blood samples taken from child and parents

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of couples who will accept to participate to the TREAT-panel gNBS	Through study completion, on average of 9 months
Number of newborns in whom a pathogenic or likely pathogenic variant in appropriate inheritance model will be identified through TREAT-panel	Through study completion, on average of 9 months
Number of child resulted negative at the TREAT-panel gNBS who develop early symptoms leading to the diagnosis a rare genetic disease by GS	Through study completion, on average of 26 months

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Dijon

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: July 23, 2024
• First Submitted That Met QC Criteria: July 26, 2024
• First Posted (Actual): July 30, 2024

Study Record Updates

• Last Update Posted (Estimated): January 23, 2025
• Last Update Submitted That Met QC Criteria: January 21, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Disease Susceptibility; Rare Diseases; Genetic Predisposition to Disease
• Other Study ID Numbers: OLIVIER FAIVRE IMI 2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No