Case-ControlDevelopmental medicine and child neurology2025

Alterations in cortical and subcortical neuroanatomy and associations with behavior in females with fragile X syndrome.

Kristi L Bartholomay, Tracy L Jordan, Lara C Foland-Ross and 3 others

PMID 39279261

WHAT IT FOUND

Females with fragile X syndrome had distinct cortical and subcortical brain patterns compared with matched females.

Brain measures tracked cognition, academics, social function, and mood in fragile X; in comparison females, only a social avoidance pattern appeared.

Key findings

01Females with fragile X syndrome had larger cortical gray matter volume in posterior occipital areas and smaller volume in frontal, temporal, insular, and central regions than comparison females.

02Females with fragile X syndrome had smaller pial surface area in seven regions and no regions with larger surface area.

03Total pial surface area and total gray matter volume were associated with cognition, academics, social function, and mood in females with fragile X syndrome.

STILL TO COME

How it was doneWhat they found

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What it does not show

The comparison group was not typically developing; it included females with other genetic conditions, parent-reported diagnoses, or special educational needs. The fragile X group was recruited across North America, while the comparison group was recruited locally, which could affect the findings. The sample was mostly White, and most parents had at least a four-year college degree, limiting generalizability. Some participants were excluded because scans could not be completed due to anxiety, braces or other MRI contraindications, or motion artifacts. The study did not measure activation ratio in females with fragile X syndrome, which can affect phenotype severity. The brain behaviour links were exploratory and do not show cause.

The easy way to misread this

Do not treat these brain patterns as a diagnostic test or as proof that a treatment works. The study compared groups at one time point, and the brain behaviour links were exploratory.

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The study

Participants
45 females with fragile X syndrome and 33 comparison females with usable scans
Certainty of evidence
Low

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    Cite

    Kristi L Bartholomay, Tracy L Jordan, Lara C Foland-Ross, et al. Alterations in cortical and subcortical neuroanatomy and associations with behavior in females with fragile X syndrome. Developmental medicine and child neurology. 2025.

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