Research on the Molecular Mechanism of Cognitive Differences Between Williams Syndrome and Autism Spectrum Disorder

N/ANot Yet RecruitingNCT07509879

Qilu Hospital of Shandong University75 enrolled

Overview

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 Type

OBSERVATIONAL

Enrollment

Conditions

Williams Syndrome Autism Disorder

Eligibility

Sex: ALLMin age: 3 YearsMax age: 12 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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)

Time frame: 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.

Time frame: baseline

Secondary Outcomes

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)

Time frame: 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)

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Baseline

Research on the Molecular Mechanism of Cognitive Differences Between Williams Syndrome and Autism Spectrum Disorder

Overview

Conditions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes