Genetic Newborn Screening for Rare Diseases Within the Screen4Care Project (SCREEN4CARE)

Shortening the Path to Rare Disease Diagnosis by Using Newborn Genetic Screening and Digital Technologies (SCREEN4CARE): Genetic Newborn Screening for Rare Diseases Within the Screen4Care Project

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.

Study Overview

• Status: Recruiting
• Conditions: Newborn Screening
• Intervention / Treatment: Diagnostic test: newborn genetic screening and whole genome sequencing

• Study Type: Interventional
• Enrollment (Estimated): 20000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alessandra Ferlini, Professor; Phone Number: +39 0532 974439; Email: screen4care@unife.it

Study Locations

• France
  • Dijon, France, 21079
    • Completed
    • Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, Hôpital d'Enfants
• Germany
  • Berlin, Germany, 13353
    • Recruiting
    • Charité University Medicine Berlin
    • Contact: Peter Kühnen, Prof. Dr.; Phone Number: 0049 30 450 666 839; Email: peter.kuehnen@charite.de
    • Contact: Janka K Hindricks, Dr.; Email: janka-katharina.hindricks@charite.de
  • Freiburg im Breisgau, Germany, 79106
    • Recruiting
    • Clinic for Neuropediatrics and Muscular Diseases, Freiburg University Medical Center
    • Contact: Kathrin Freyler, Dr.; Email: kathrin.freyler@uniklinik-freiburg.de
    • Contact: Janbernd Kirschner, Professor; Phone Number: +49 761 270-43650; Email: kjk.screen4care@uniklinik-freiburg.de
    • Principal Investigator: Janbernd Kirschner, Professor
  • Göttingen, Germany, 37075
    • Recruiting
    • University Medical Center Göttingen, Clinic for Neurology
    • Contact: Jana Zschüntzsch, Priv.-Doz. Dr.; Phone Number: 00495513965167; Email: j.zschuentzsch@med.uni-goettingen.de
    • Contact: Elisabeth Nyoungui; Email: elisabeth.nyoungui@med.uni-goettingen.de
• Italy
  • Ferrara, Italy, 44122
    • Completed
    • Unit Medical Genetics, Azienda Ospedaliero-Universitaria Sant'Anna
  • Modena, Italy, 41100
    • Recruiting
    • Azienda Ospedaliero Universitaria di Modena, Neonatology Unit
    • Contact: Prof. Alberto Berardi; Email: alberto.berardi@unimore.it
    • Contact: Dr Licia Lugli; Email: licia.lugli@gmail.com
  • Roma, Italy, 00189
    • Recruiting
    • San Pietro Fatebenefratelli Hospital
    • Contact: Prof. Marco Bonito, UOC Obstetrics and Gynecology; Email: bonito.marco@fbfrm.it
    • Contact: Dott.ssa Maria Eleonora Scapillati, UOC Pediatrics and Neonatology; Email: scapillati.eleonora@fbfrm.it
  • Lazio
    • Rome, Lazio, Italy, 00165
      • Recruiting
      • Ospedale Pediatrivo Bambino Gesu IRCCS
      • Contact: Enrico S Bertini; Phone Number: +39 0668592104; Email: enricosilvio.bertini@opbg.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• TREAT-panel:

  • newborns
  • Infants born in one of the participating hospitals and birth centres
  • Informed consent signed by both parents/legal guardian to participate in genetic newborn screening (TREAT-panel)

• Whole genome sequencing:

  • Participation in the TREAT-panel study
  • Symptoms suggestive of a genetic disease within the first 2 years of life
  • Informed consent signed by both parents/legal guardian to participate in genetic newborn screening (TREAT-panel) and the whole genome sequencing

Exclusion Criteria:

• Missing informed consent of parents/legal guardian

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: newborn screening; All newborns participating in the study will receive a genetic newborn screening for predefined treatable diseases. Newborns participating in the TREAT-panel developing symptoms suggestive of a genetic disease during the first 2 years of life can receive whole genome sequencing.	Diagnostic test: newborn genetic screening and whole genome sequencing; newborn genetic screening (panel of treatable diseases); whole genome sequencing (if newborn develops symptoms suggestive of a genetic disease)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: University Hospital Freiburg
• Collaborators: Charite University, Berlin, Germany; Centre Hospitalier Universitaire Dijon; Università degli Studi di Ferrara; Brno University Hospital; Illumina, Inc.; Innovative Medicines Initiative; University of Rzeszow; University of Siena; University Hospital Goettingen; San Camillo Hospital, Rome; Hospital San Pietro Fatebenefratelli; General Hospital Of Thessaloniki Ippokratio; Ospedale Pediatrico Bambin Gesù; Centro Nacional de Análisis Genómico; Real Genix; Genoox; Municipal Hospital Karlsruhe; Schwarzwald-Baar Hospital
• Investigators: Principal Investigator: Alessandra Ferlini, Professor, Unit Medical Genetics, Azienda Ospedaliero-Universitaria Sant'Anna

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: July 29, 2024
• First Submitted That Met QC Criteria: August 7, 2024
• First Posted (Actual): August 12, 2024

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Rare Diseases
• Other Study ID Numbers: 101034427

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