Characterization of the Natural History of Microduplication Syndrome 7q11.23

NCT07469566 | Not Yet Recruiting

• 2 other identifiers: 69HC24_09912025-A01944-45
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

7q11.23 duplication syndrome (7q duplication syndrome/7DUP) is caused by a microduplication of the 7q11.23 chromosomal region, encompassing 26-28 genes, including the GTF2I gene. This syndrome, often considered as a "mirror" phenotype of Williams-Beuren syndrome (WBS), is characterized by a wide range of neurodevelopmental impairments, including a neurodevelopmental disorder (NDD), autism spectrum disorders (ASD), selective mutism, mild dysmorphic features, and aortic dilation. Notably, one of the core clinical features of 7DUP is socialization impairment, which varies in severity across individuals. The GTF2I gene, identified as critical in the pathogenesis of both WBS and 7DUP, exhibits opposite expression patterns in the two syndromes, with reduced expression in WBS and overexpression in 7DUP. The gene's dysregulation in 7DUP plays a pivotal role in the pathogenesis of the associated NDD and social deficits. Despite progress in characterizing the genetic underpinnings of 7DUP, there remains a critical gap in understanding the developmental trajectory of socialization impairments in affected individuals, especially during their transition through different developmental stages, from early childhood to adulthood. Recent advancements in the study of neuronal models derived from induced pluripotent stem cells (iPSCs) and brain organoids have shed light on the molecular mechanisms driving 7DUP-related NDDs. Histone deacetylase inhibitors (HDAC inhibitors), which have been widely used in oncology, have shown promising preliminary results in reducing abnormal GTF2I expression in glutamatergic neurons differentiated from 7DUP patient-derived iPSCs. Preclinical studies in mouse models further demonstrated that these drugs can ameliorate socialization deficits, highlighting their therapeutic potential in addressing the core neurodevelopmental challenges in 7DUP. However, despite these advancements, no longitudinal clinical studies have characterized the developmental trajectory of socialization impairments in 7DUP patients. Understanding this trajectory is critical, as it can inform the timing and potential impact of therapeutic interventions, such as HDAC inhibitors. Given the complexity and variability of the 7DUP phenotype, a comprehensive clinical characterization of socialization impairments across the lifespan is essential to improve diagnostic accuracy, optimize intervention strategies, and ultimately improve patient outcomes. The aim of this research is to characterize the developmental trajectory of socialization impairments in patients with 7DUP, from early childhood through adulthood. By identifying patterns of socialization difficulties, this innovative study will allow to efficiently prepare future therapeutic trials, by specifying the phenotype of the patients, and by determining the most relevant outcome measures, taking into account, on one hand, their neurodevelopmental involvement and, on the other hand, the type of experimental design to be used in the context of rare diseases.

Conditions

7q11.23 Microduplication Syndrome (7DUP); Autism Spectrum Disorder (ASD); Neurodevelopmental Disorders (NDD)

Keywords

7q11.23 microduplication; 7DUP syndrome; neurodevelopmental disorders; autism spectrum disorder; ASD

Outcome Measures

Primary Outcomes (8)

• Developmental trajectory tracking through age of acquisition in months.

  \- Age at head control acquisition in months,

  At inclusion visit

• Developmental trajectory tracking

  \- Age at sitting alone in months,

  At inclusion visit

• Developmental trajectory tracking

  \- Age at walking alone in months,

  At inclusion visit

• Developmental trajectory tracking

  \- Age at running in months,

  At inclusion visit

• Developmental trajectory tracking

  \- Age at climbing stairs alternately in months,

  At inclusion visit

• Adaptive assessment of skills (communication, daily life, socialisation, and motor skills)

  * based on interview with the parents of the patient * and with the VABS2 (Vineland Adaptive Behaviour Scale second edition)

  At inclusion visit

• Description of the global social assessment from the ADOS scale score [0-28]

  * Social assessment: score \[0-28\] from the ADOS scale (Autism Spectrum Disorder) * A score \>7 indicated characteristics of autism spectrum disorder.

  At inclusion visit

• Description of the global autism spectrum disorder (ASD)

  * through parental questionnaires * score (range 0-19) derived from the Pervasive Developmental Disorder in Mentally Retarded Persons Scale (PDD-MRS). * A score \> 10 is positive for an autism spectrum disorder.

  At inclusion visit

Secondary Outcomes (5)

• Full-Scale Intelligence Quotient (FSIQ)

  At inclusion visit

• Nonverbal Intelligence Quotient (NVIQ)

  At inclusion visit

• Epilepsy Status

  At inclusion visit

• Atypical Sensory Profile Type

  At inclusion visit

• 24-Hour Activity and Sleep Duration (Minutes)

  At inclusion visit

Study Arms (1)

7q11.23 Microduplication Syndrome Patients (7DUP)

EXPERIMENTAL

Patients aged 5 to 50 years with a confirmed diagnosis of 7q11.23 microduplication syndrome (7DUP).

Other: clinical assessment; Other: Parental questionnaires; Other: Cognitive assessment; Device: Reasoning assessment; Other: Motor assessment; Other: Social assessment; Other: Brain MRI (structural and functional)

Interventions

clinical assessment OTHER

Clinical examination including Medical history, developmental trajectory, epilepsy history, clinical examination, actimetry over 24hours, podometry, 6 minutes walk test at the inclusion visit by a neuropediatrist.

7q11.23 Microduplication Syndrome Patients (7DUP)

Parental questionnaires OTHER

Parental questionnaires including Vineland Adaptive Behavior scale second edition (Vineland II) , SRS-2, CBI, Beach Center Family Quality Of Life , PPD-MRS, Dunn sensory profile, ABC, Nisonger Child Behavior Rating, PEDSQL, Pediatric Quality of Life Inventory , San Martin Scale completed at the inclusion visit.

7q11.23 Microduplication Syndrome Patients (7DUP)

Cognitive assessment OTHER

Cognitive assessment including Leiter-3, Bayley-4 (if Leiter-3 not possible), CPM-BF, 4 sub-tests from the WPPSI-IV, 4 sub-tests from KITAP.PPVT 5, EVT 3, EXALANG 3-6 and automatic language analysis will be performed at the inclusion visit.

7q11.23 Microduplication Syndrome Patients (7DUP)

Reasoning assessment DEVICE

Simple reasoning tasks on tablets performed at the inclusion visit.

7q11.23 Microduplication Syndrome Patients (7DUP)

Motor assessment OTHER

Purdue-Pegboard test , Kinematic task and Renzi scale will be performed at inclusion visit.

7q11.23 Microduplication Syndrome Patients (7DUP)

Social assessment OTHER

Two eye-tracking tasks, ADOS, theory of mind assessment will be performed at inclusion visit.

7q11.23 Microduplication Syndrome Patients (7DUP)

Brain MRI (structural and functional) OTHER

Optional brain MRI acquisition (structural and functional) will be performed at inclusion visit.

7q11.23 Microduplication Syndrome Patients (7DUP)

Eligibility Criteria

• Age: 5 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of 7q11.23 microduplication confirmed by Chromosomal Microarray Analysis or qPCR.
• Aged \> 5 to \< 50 years
• Whose maternal language is French
• Having signed the informed consent and/or for whom parents/legal guardian have signed the informed consent.
• Affiliated to national Health Insurance system (sécurité sociale) or parents/legal guardian affiliated to national health insurance system Each 7DUP patient will be matched to a sex- and chronological age-matched control. Data from controls will come from the CREAT\_criteria study (NCT 06018519). Each 7DUP patient will be matched to a sex- and mental age-matched control. Data from controls will come from the CREAT\_criteria study (NCT 06018519).

You may not qualify if:

• Refusal of the subject and/or the subject's parents/legal guardian to sign the informed consent
• Refusal of the subject and/or the subject's parents/legal guardian to be informed of possible abnormalities detected during the neuropsychological assessment.
• Regarding specifically the neuroimaging data (MRI):
• Having a contraindication to the MRI examination (people using a pacemaker or an insulin pump, people wearing a metal prosthesis or an intracerebral clip, and claustrophobic subjects).
• Refusal of the subject and/or the subject's parents/legal guardian to be informed of possible abnormalities detected by MRI.

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (2)

Developmental Anomalies Reference Center, Genetics Department Woman Mother and Child Hospital, University Hospital of Lyon, Hospices Civils de Lyon

Bron, 69677, France

Location

Reference Center of Rare Disease with Intellectual Disability- in Lyon, Woman Mother and Child Hospital, University Hospital of Lyon, Hospices Civils de Lyon

Bron, 69677, France

Location

MeSH Terms

Conditions

Williams-Beuren Region Duplication Syndrome; Autism Spectrum Disorder; Neurodevelopmental Disorders

Interventions

Mental Status and Dementia Tests; Functional Status

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Mental Disorders

Intervention Hierarchy (Ancestors)

Neuropsychological Tests; Psychological Tests; Behavioral Disciplines and Activities; Activities of Daily Living; Rehabilitation; Health Services; Health Care Facilities Workforce and Services; Health Status; Demography; Epidemiologic Measurements; Public Health; Environment and Public Health

Central Study Contacts

Dr Massimiliano ROSSI

CONTACT

+33 (0)4.27.85.55.72; massimiliano.rossi01@chu-lyon.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Only one prospective group included in this protocol. The control data come from CREAT\_criteria study (NCT06018519)

Study Record Dates

• First Submitted: December 5, 2025
• First Posted: March 13, 2026
• Study Start: March 15, 2026
• Primary Completion (Estimated): July 15, 2027
• Study Completion (Estimated): July 15, 2027
• Last Updated: March 13, 2026

Record last verified: 2026-03

Locations

FR (2)