Characterization of the Natural History of Microduplication Syndrome 7q11.23 (HINADU7)

Characterization of the Natural History of Microduplication Syndrome

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Autism Spectrum Disorder (ASD); 7q11.23 Microduplication Syndrome (7DUP); Neurodevelopmental Disorders (NDD)
• Intervention / Treatment: Other: clinical assessment; Other: Parental questionnaires; Other: Cognitive assessment; Device: Reasoning assessment; Other: Motor assessment; Other: Social assessment; Other: Brain MRI (structural and functional)

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dr Massimiliano ROSSI; Phone Number: +33 (0)4.27.85.55.72; Email: massimiliano.rossi01@chu-lyon.fr

Study Locations

• France
  • Bron, France, 69677
    • Developmental Anomalies Reference Center, Genetics Department Woman Mother and Child Hospital, University Hospital of Lyon, Hospices Civils de Lyon
    • Contact: Dr Massimiliano ROSSI
  • Bron, France, 69677
    • Reference Center of Rare Disease with Intellectual Disability- in Lyon, Woman Mother and Child Hospital, University Hospital of Lyon, Hospices Civils de Lyon
    • Contact: Dr Aurore CURIE

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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).

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

Other: clinical assessment; 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.; Other: Parental questionnaires; 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.; Other: Cognitive assessment; 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.; Device: Reasoning assessment; Simple reasoning tasks on tablets performed at the inclusion visit.; Other: Motor assessment; Purdue-Pegboard test , Kinematic task and Renzi scale will be performed at inclusion visit.; Other: Social assessment; Two eye-tracking tasks, ADOS, theory of mind assessment will be performed at inclusion visit.; Other: Brain MRI (structural and functional); Optional brain MRI acquisition (structural and functional) will be performed at inclusion visit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Full-Scale Intelligence Quotient (FSIQ)	The Full-Scale Intelligence Quotient (FSIQ) is a standardized measure of global cognitive functioning, with scores ranging from 40 to 160. It is assessed using age-appropriate Wechsler scales: Wechsler Preschool and Primary Scale of Intelligence Fourth Edition (WPPSI-IV) for children aged 5-6 years, Wechsler Intelligence Scale for Children Fifth Edition (WISC-V) for children older than 6 years, and Wechsler Adult Intelligence Scale Fourth Edition (WAIS-IV) for individuals older than 16 years. An IQ score below 70 is indicative of intellectual disability.	At inclusion visit
Nonverbal Intelligence Quotient (NVIQ)	The Nonverbal Intelligence Quotient (NVIQ) is a standardized measure of nonverbal cognitive functioning, with scores ranging from 30 to 170. It is assessed using the Leiter International Performance Scale Third Edition (Leiter-3) when Wechsler scales cannot be administered. The assessment includes four cognitive subtests to derive the nonverbal IQ score and two additional subtests evaluating nonverbal memory. An IQ score below 70 is indicative of intellectual disability.	At inclusion visit
Epilepsy Status	Epilepsy status is recorded as a dichotomous variable (Yes/No) based on information extracted from the participant's medical file at the inclusion visit. This outcome reflects the presence or absence of a documented diagnosis of epilepsy at the time of study enrollment.	At inclusion visit
Atypical Sensory Profile Type	The type of atypical sensory profile (auditory, visual, tactile, and movement-related) is determined using the Dunn Sensory Profile. This assessment is based on parent-completed questionnaires evaluating patterns of hypo- and hypersensitivity across the specified sensory domains.	At inclusion visit
24-Hour Activity and Sleep Duration (Minutes)	Total duration of physical activity (minutes) and total sleep duration (minutes) over a 24-hour period, measured using actimetry data collected at the inclusion visit. This outcome is derived from objective actigraphy recordings quantifying movement-based activity and sleep patterns across a continuous 24-hour monitoring period.	At inclusion visit

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Estimated): March 15, 2026
• Primary Completion (Estimated): July 15, 2027
• Study Completion (Estimated): July 15, 2027

Study Registration Dates

• First Submitted: December 5, 2025
• First Submitted That Met QC Criteria: March 10, 2026
• First Posted (Actual): March 13, 2026

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: autism spectrum disorder; ASD; neurodevelopmental disorders; 7q11.23 microduplication; 7DUP syndrome
• Additional Relevant MeSH Terms: Mental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Neurodevelopmental Disorders; Williams-Beuren Region Duplication Syndrome; Public Health; Environment and Public Health; Health Services; Health Care Facilities Workforce and Services; Behavioral Disciplines and Activities; Rehabilitation; Health Status; Demography; Epidemiologic Measurements; Psychological Tests; Activities of Daily Living; Neuropsychological Tests; Functional Status; Mental Status and Dementia Tests
• Other Study ID Numbers: 69HC24_0991; 2025-A01944-45 (Other Identifier: ID-RCB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No