Research on the Molecular Mechanism of Cognitive Differences Between Williams Syndrome and Autism Spectrum Disorder (WS and ASD)

Williams Syndrome (WS) is a rare neurodevelopmental disorder, usually caused by microdeletions of approximately 26 genes in the long arm (7q11.23) region of chromosome 7. Children with this syndrome often exhibit distinctive facial features, mild to moderate intellectual disability, impaired spatial cognition, pronounced social extraversion, and relatively reserved language-expression characteristics. Although individuals with WS often demonstrate strong social interest and prosocial behaviors, significant deficiencies in abstract thinking, executive function, and visuospatial ability are frequently observed. At present, treatment for WS mainly focuses on behavioral intervention and educational rehabilitation, and clear molecular or pharmacological treatment methods remain limited. Due to the "opposite but related" social-cognitive profile observed in comparison with autism spectrum disorder, in-depth exploration of neural and molecular mechanisms underlying these differences has substantial scientific significance for understanding the biological basis of social-cognitive impairment.

Study Overview

• Status: Not yet recruiting
• Conditions: Williams Syndrome; Autism Disorder

• Study Type: Observational
• Enrollment (Estimated): 75

Contacts and Locations

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250012
      • Qilu Hospital of Shandong University
      • Contact: Ai Cao; Phone Number: 18560086317; Email: qlyyebk@163.com

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Source of research participants: WS research participants, ASD research participants and normal children controls who visited the pediatric health rehabilitation clinic

Description

Participants for Williams Syndrome Study

Inclusion criteria must all be met:

1. Age 3-12 years old.
2. Clinically diagnosed and confirmed by fluorescence in situ hybridization (FISH) test, with a typical microdeletion of approximately 1.55 Mb in the chromosome 7q11.23 region.
3. Their legal guardians fully understand the study content and voluntarily sign the informed consent form, agreeing for the study participants to undergo blood sampling and genetic testing.

Participants for Autism Spectrum Disorder Study

Inclusion criteria must all be met:

1. Age 3-12 years old.
2. Clinically diagnosed according to the second edition of the Autism Diagnostic Observation Schedule (ADOS-2) criteria.
3. Their legal guardians fully understand the study content and voluntarily sign the informed consent form, agreeing for the study participants to undergo blood sampling and genetic testing.

Participants for Healthy Children Study

Inclusion criteria must all be met:

1. Age 3-12 years old, with gender as close as possible to the participants in the above two groups.
2. No history of neurodevelopmental disorders, mental illnesses or major neurological diseases.
3. Their legal guardians fully understand the study content and voluntarily sign the informed consent form, agreeing for the study participants to undergo blood sampling and genetic testing.

Common Exclusion Criteria for All Study Participants

Any of the following conditions must be met to be excluded from the study:

1. Specific medical conditions:
2. For the Williams Syndrome group: Known or suspected presence of other pathogenic gene mutations/syndromes other than the 7q11.23 microdeletion.
3. For the Autism Spectrum Disorder group: Co-occurring other clearly diagnosed neurodevelopmental disorders (such as Rett syndrome, fragile X syndrome, etc.).
4. Brain structural abnormalities: According to recent cranial MRI and interpretation by neuro-radiology experts, significant brain structural lesions are found (for the patient group, referring to lesions unrelated to Williams Syndrome or autism; for the healthy group, referring to any clinically significant abnormalities).
5. Major systemic diseases: Presence of diseases with clinical significance as judged by the researchers, which may: affect the interpretation of study results, or endanger the safety of the study participants.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Williams Syndrome; After clinical diagnosis and confirmation through fluorescence in situ hybridization (FISH) testing, a typical microdeletion of approximately 1.55 Mb in the chromosome 7q11.23 region was identified.
Autism Spectrum disorder; It meets the clinical diagnostic criteria of the Second Edition of the Autism Diagnostic Observation Scale (ADOS-2).
healthy children; There is no history of neurodevelopmental disorders, mental illness or major neurological diseases

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The score of Motor Quotient in Peabody Developmental Motor Scales, Second Edition (PDMS-2)	Motor development will be assessed using the Peabody Developmental Motor Scales, Second Edition (PDMS-2). The endpoint is the Motor Quotient (range: 50-150). Higher scores indicate better motor functioning (i.e., better outcome). Group differences will be evaluated across WS, ASD, and typically developing controls.	Baseline
The score of Developmental Quotient (DQ) in Gesell Developmental Schedules (GDS)	Neurodevelopmental level will be assessed using the Gesell Developmental Schedules (Gesell Developmental Scale). The endpoint is the Developmental Quotient (DQ) (range: 0-130). Higher scores indicate better developmental functioning (i.e., better outcome). Group differences will be evaluated across WS, ASD, and typically developing controls.	Baseline
Fractional Anisotropy (FA)	White matter microstructural integrity will be quantified using DTI-derived fractional anisotropy (FA). FA values range from 0 to 1, with higher values indicating greater directional diffusion and typically better white matter integrity (i.e., better outcome). Group differences will be evaluated across WS, ASD, and typically developing controls. Unit of Measure : mm²/s (typically reported as ×10-³ mm²/s)	baseline
The score pf Social Responsiveness Scale, Second Edition (SRS-2)	Social communication will be assessed using the Social Responsiveness Scale, Second Edition (SRS-2). The primary endpoint is the SCI T-score (range: 0-100). Higher scores indicate worse social communication impairment (i.e., poorer outcome). Group differences will be compared across WS, ASD, and typically developing controls.	baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diffusion Tensor Imaging (DTI) Axial Diffusivity (AD)	White matter microstructural properties will be quantified using DTI-derived axial diffusivity (AD). AD will be summarized as the mean AD within prespecified white matter regions of interest (ROIs) (or whole-brain white matter skeleton, if applicable). Higher AD indicates greater diffusion along the principal axis; interpretation (better/worse) is direction-dependent and will be interpreted in the context of neurodevelopmental findings. Unit of Measure: mm²/s (typically reported as ×10-³ mm²/s)	Baseline
Diffusion Tensor Imaging (DTI) Mean Diffusivity (MD)	DTI-derived mean diffusivity (MD) will be calculated and summarized as the mean MD within prespecified white matter ROIs (or whole-brain white matter skeleton, if applicable). Higher MD indicates greater overall water diffusion and is commonly interpreted as reduced microstructural integrity (worse outcome). Unit of Measure: mm²/s (typically reported as ×10-³ mm²/s)	Baseline
Diffusion Tensor Imaging (DTI) Radial Diffusivity (RD)	DTI-derived radial diffusivity (RD) will be calculated and summarized as the mean RD within prespecified white matter ROIs (or whole-brain white matter skeleton, if applicable). Higher RD indicates greater diffusion perpendicular to the principal axis and is often interpreted as poorer myelination or reduced microstructural integrity (worse outcome).Unit of Measure: mm²/s (typically reported as ×10-³ mm²/s)	Baseline
Structural MRI (sMRI) Cortical Volume	Cortical morphology will be quantified from T1-weighted structural MRI. Cortical volume will be computed using an automated cortical reconstruction pipeline (e.g., FreeSurfer) and summarized as mean cortical volume (mm³) within prespecified cortical ROIs (or total cortical gray matter volume, if applicable). Higher cortical volume indicates greater cortical tissue volume. Unit of Measure: mm³	Baseline
Structural MRI (sMRI) Cortical Thickness	Cortical morphology will be quantified from T1-weighted structural MRI. Cortical thickness will be computed and summarized as mean cortical thickness (mm) within prespecified cortical ROIs (or mean global cortical thickness, if applicable). Higher thickness indicates greater cortical thickness;Unit of Measure: mm	Baseline
Structural MRI (sMRI) Subcortical Structure Volume	Subcortical anatomy will be quantified from T1-weighted structural MRI. Subcortical structure volumes (e.g., amygdala, hippocampus, thalamus, caudate, putamen, pallidum) will be computed using an automated segmentation pipeline (e.g., FreeSurfer) and summarized as volume (mm³) for prespecified subcortical regions. Higher volume indicates greater structure volume; Unit of Measure: mm³	Baseline

Collaborators and Investigators

• Sponsor: Qilu Hospital of Shandong University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 23, 2026
• First Submitted That Met QC Criteria: March 29, 2026
• First Posted (Actual): April 3, 2026

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: March 29, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Genetics; Autism Spectrum Disorder; Neuroimaging; Williams Syndrome
• Additional Relevant MeSH Terms: Aortic Valve Disease; Neurologic Manifestations; Nervous System Diseases; Cardiovascular Diseases; Mental Disorders; Heart Diseases; Genetic Diseases, Inborn; Neurobehavioral Manifestations; Heart Valve Diseases; Congenital Abnormalities; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Intellectual Disability; Aortic Valve Stenosis; Chromosome Disorders; Aortic Stenosis, Supravalvular; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Autism Spectrum Disorder; Autistic Disorder; Williams Syndrome
• Other Study ID Numbers: QL000007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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