Developmental and Epileptic Encephalopathies Diagnosed Via Long-read Genome Sequencing

NCT07396883 | Not Yet Recruiting

• 1 other identifier: 9964
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 4

Brief Summary

This study focuses on children with Developmental and Epileptic Encephalopathy (DEE), a severe form of epilepsy that often has a genetic origin. Currently, standard diagnostic tools-known as short-read genome sequencing-fail to provide a diagnosis for over 50% of affected patients because they cannot detect certain complex DNA abnormalities. The purpose of this study is to evaluate the effectiveness of a newer, more advanced technology called Long-read Genome Sequencing (lrWGS). Unlike traditional methods, this technology analyzes very long fragments of DNA, allowing researchers to identify genetic errors that were previously "invisible." The study aims to answer whether Long-read Sequencing can successfully identify the genetic cause of epilepsy in patients who have already received a negative result from standard testing. By finding these missing answers, the research seeks to enable personalized medical treatments, improve genetic counseling for families, and advance our understanding of how these complex neurological conditions develop.

Conditions

Epilepsy in Children; Developmental and Epileptic Encephalopathy

Keywords

Developmental and Epileptic Encephalopathy (DEE); Drug-Resistant Epilepsy; Long-read Whole Genome Sequencing (lrWGS); Long-read Sequencing; Negative Short-read Sequencing; Genetic Diagnosis; Pediatric Neurology; High-Throughput Nucleotide Sequencing; Early-Onset Epilepsy; Genetic Epilepsy

Outcome Measures

Primary Outcomes (1)

• Number of pathogenic and likely pathogenic genetic variants identified by long-read whole genome sequencing (lrWGS)

  Evaluate the efficacy of long-read whole genome sequencing (lrWGS) in identifying genetic causes in patients with developmental and epileptic encephalopathy who did not obtain a molecular diagnosis despite previous short-read whole genome sequencing (srWGS) analysis within the framework of the French Genomic Medicine Plan 2025 (PFMG 2025).

  At the results delivery visit (Visit 1), up to 15 months after enrollment.

Study Arms (1)

DEE Long-read

his cohort is composed of pediatric patients (under 18 years old) with Developmental and Epileptic Encephalopathy (DEE) as defined by the 2022 ILAE criteria. The group is specifically characterized by a prior negative molecular diagnosis despite analysis via short-read Whole Genome Sequencing (srWGS) through the French Genomic Medicine Plan 2025 (AURAGEN platform). Selection follows a clinical prioritization strategy: while the study includes all eligible DEE patients without a genetic answer, priority is given to those with early-onset forms, familial cases, or current therapeutic impasse (patients for whom standard treatments have failed). The study excludes cases where a clear non-genetic cause is identified, such as perinatal brain injury, focusing the cohort on high-probability "hidden" genetic etiologies.

Diagnostic Test: Long-read Whole Genome Sequencing (lrWGS)

Interventions

Long-read Whole Genome Sequencing (lrWGS) DIAGNOSTIC_TEST

Long-read Whole Genome Sequencing (lrWGS) using high-molecular-weight DNA previously extracted and banked during the patient's initial clinical workup.

DEE Long-read

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The study population is drawn from specialized pediatric neurology and genetics departments within the French university hospital network (CHU). Participants are specifically sourced from the existing patient base of the AURAGEN platform, one of the two national sequencing hubs established under the French Genomic Medicine Plan 2025 (PFMG 2025). These individuals represent a highly selected sub-population of children across France who have already undergone extensive clinical phenotyping and "first-line" genomic screening but remain without a molecular diagnosis. The recruitment occurs primarily at the Strasbourg University Hospital (Hôpitaux Universitaires de Strasbourg) and collaborating clinical sites. These centers serve as regional and national referral points for rare and refractory childhood epilepsies, ensuring that the study population includes the most complex and diagnostically challenging cases of Developmental and Epileptic Encephalopathy (DEE) in the country.

You may qualify if:

• Pediatric Participants:
• Age \< 18 years.
• Diagnosis of Developmental and Epileptic Encephalopathy (DEE) according to 2022 ILAE criteria (severe epilepsy, encephalopathic EEG, multiple drug-resistant seizures, and neurodevelopmental disorder).
• Brain MRI without markers of perinatal anoxia.
• Negative molecular diagnosis after short-read Whole Genome Sequencing (srWGS) via the French Genomic Medicine Plan 2025 (AURAGEN).
• Available banked DNA at a participating center.
• Parents/Legal Guardians:
• Age ≥ 18 years.
• Able to understand study objectives and risks.
• Signed and dated informed consent.
• Affiliated with or beneficiary of a social security scheme.

You may not qualify if:

• Pediatric Participants:
• Brain MRI findings in favor of perinatal cerebral anoxia.
• Intercurrent diseases preventing the completion of protocol examinations.
• Parents/Legal Guardians:
• Inability to receive or understand informed information (e.g., life-threatening emergency).
• Subject under judicial protection, tutelage, or curatorship.
• Language barriers where an official interpreter is unavailable.

Sponsors & Collaborators

• University Hospital, Strasbourg, France: lead
• IGBMC: collaborator
• Laboratoire de diagnostic génétique - NHC: collaborator
• Groupe Méthode en Recherche Clinique (GMRC): collaborator
• Bio-informatique médicale appliquée au diagnostic (UF7363) - NHC: collaborator

Study Sites (4)

CHU Jean Minjoz

Besançon, 25000, France

Location

American Memorial Hospital

Reims, 51092, France

Location

Hôpitaux Universitaires de Strasbourg

Strasbourg, 67098, France

Location

CHU de Nancy - hôpital d'enfant

Vandœuvre-lès-Nancy, 54511, France

Location

MeSH Terms

Conditions

Drug Resistant Epilepsy

Condition Hierarchy (Ancestors)

Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Central Study Contacts

Sarah BAER

CONTACT

+333.88.12.84.98; sarah.baer@chru-strasbourg.fr

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2026
• First Posted: February 9, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: February 9, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (4)