MOLECULAR BASIS OF LANGUAGE DEVELOPMENT AND ASSOCIATED DISORDERS (TSLO)

BASES MOLECULAIRES DU DEVELOPPEMENT DU LANGAGE ORAL ET DES TROUBLES SPECIFIQUES ASSOCIES

Developmental Language Disorder (DLD) refers to children who present with language difficulties that are not due to a known biomedical condition or associated with autism spectrum disorder (ASD) or intellectual disability. The prevalence of DLD is ~7%-8% or 2% if severe forms are considered.

However, the clinical heterogeneity of language disorders, the presence of co-morbidities and the inconsistent terminology used for many years have hindered research and clinical practice. Distinguishing sub-groups of children with language problems is crucial when tackling the underlying genetic causes of this disease. Recently, several studies using high-throughput sequencing have better define the genetic basis of CAS but such studies focusing on DLD are limited. The investigation of more homogeneous cohorts of individuals that clearly distinguish DLD cases, from ID and not including children with CAS should improve our understanding of the genetic basis of this disorder.

In this study, we aim to built and investigate a well-characterized cohort of DLD patients using pangenomic approaches to better define the molecular basis of this disorder. All individuals will be analyzed using chromosomal microarray analysis and whole genome sequencing. Multiple observations and preliminary results suggest strong links with the genetic basis of other neurodevelopmental disorders.

The goal is to identify CNV or SNV as causative allele or risk factor and already known to be involved in other neurodevelopmental disorders as well as potential new variants.

Study Overview

• Status: Recruiting
• Conditions: Developmental Language Disorder
• Intervention / Treatment: Genetic: blood draw

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Vincent Cantagrel, PhD; Phone Number: 33 142754237; Email: vincent.cantagrel@inserm.fr

Study Locations

• France
  • Corbeil-Essonnes, France, 91100
    • Recruiting
    • Hôpital Sud Francilien
    • Contact: Christine CONTI, Dr; Phone Number: 01 69 31 02 63; Email: christine.conti@chsf.fr
  • Garches, France, 92380
    • Recruiting
    • Raymond Poincaré- Garches
    • Contact: Emilie SCHLUMBERGER, Dr; Phone Number: 01 47 10 76 58; Email: emilie.schlumberger@aphp.fr
  • Paris, France, 75015
    • Recruiting
    • Hopital Necker
    • Contact: Clothilde ORMIERES, DR; Phone Number: 01 44 49 54 02; Email: clothilde.ormieres@institutimagine.org

Participation Criteria

Eligibility Criteria

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

Description

Patients

Inclusion Criteria:

• Eligible families included at least one child over five years old with a formal diagnosis of severe and isolated DLD according to Phase 2 CATALISE criteria . Patients have undergone age-appropriate speech, language and reading evaluations by a speech-language physician and cognitive evaluations by a neuropsychologist, as well as evaluation by a pediatric neurologist to identify co-occurring developmental disorders (ADHD, ASD…) and a medical geneticist for known genetic disorders and genetic testing recommendations. All children included received appropriate speech therapy for at least one year, with a progress report indicating the persistence of language difficulties.

Exclusion Criteria:

• Cognitive impairment with non-verbal intellectual quotient (IQ) below 2 SD assessed with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI), or the Wechsler Intelligence Scale for Children (WISC-IV or V) according to the age-appropriateness, ASD, moderate to severe hearing loss, orofacial structural abnormalities, known neurological or genetic disorders at the initial assessment. None of the patients met the diagnostic criteria for CAS according to the ASHA (American Speech-Language-Hearing Association, 2007. Childhood apraxia of speech www.asha.org/policy).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• 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: DLD patient and relative	Genetic: blood draw; Multiple blood draw for genomic and transcriptomic investigations

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Identification of CNV or SNV involved in neurodevelopmental disorders	2 years

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Collaborators: Imagine Institute

Publications and helpful links

General Publications

• Ormieres C, Lesieur-Sebellin M, Siquier-Pernet K, Delplancq G, Rio M, Parisot M, Nitschke P, Rodriguez-Fontenla C, Bodineau A, Narcy L, Schlumberger E, Cantagrel V, Malan V. Deciphering the genetic basis of developmental language disorder in children without intellectual disability, autism or apraxia of speech. Mol Autism. 2025 Feb 13;16(1):10. doi: 10.1186/s13229-025-00642-8.

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2025
• Primary Completion (Estimated): March 25, 2027
• Study Completion (Estimated): March 25, 2028

Study Registration Dates

• First Submitted: October 24, 2024
• First Submitted That Met QC Criteria: October 24, 2024
• First Posted (Actual): October 26, 2024

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neurobehavioral Manifestations; Communication Disorders; Language Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Language Development Disorders; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: C23-79; IDRCB (Other Identifier: 2025-A01568-41)

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