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Structural Magnetic Resonance Imaging-Based Brain Morphology Study in Infants and Toddlers With Down Syndrome: The Effect of Comorbidities
Open accessAbstract
Background Down syndrome (DS) is the most prevalent chromosomal disorder characterized by intellectual disability, multiple organ anomalies, generalized muscular hypotonia, and characteristic physical features. The presence of DS-associated medical comorbidities has contributed to brain morphologic changes. The aim of this study was to evaluate brain morphologic characteristics during infant and toddler ages in patients with DS using structural brain magnetic resonance imaging. Methods Structural brain T1-weighted magnetic resonance images from participants with DS with complete chromosome 21 trisomy (n = 20; 1.6 ± 0.6 [mean ± standard deviation] years old) were analyzed using FreeSurfer. The measurements were compared with those of 60 gender- and age-matched neurotypical controls by Cohen's d statistic and unpaired t test with false discovery rate correction for multiple comparisons and analyzed using a univariate general linear model with the following DS-associated medical comorbidities: congenital cardiac disease, infantile spasms, and hypothyroidism. Results We identified 27 candidate measurements with large effect sizes (absolute d > 0.8) and statistically significant differences (P < 6.9 × 10-3). Among them were decreased volumes in bilateral cerebellar gray matter and right cerebellar white matter and brainstem and cortical abnormalities in the right superior temporal, right rostral anterior cingulate, and left rostral middle frontal gyrus, independent of comorbid effects. Only bilateral cerebellar gray matter volumes and brainstem volume showed differences between DS and healthy groups during infancy. Conclusion These results suggest that cerebellar gray matter and brainstem may represent the primary regions affected by the presence of an additional copy of chromosome 21.
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“Gross anatomical differences in brain structure are apparent in the fetal and neonatal brains of individuals with DS, including reductions in overall brain volume, white matter volume, gyral complexity, sulcal depth and growth of the cortical plate6,8–15.”
From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [15]
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Metadata
- Authors
- Shiohama, T., Levman, J., Baumer, N., & Takahashi, E.
- Affiliations
- Boston Children's Hospital (US)
- Corresponding author
- Shiohama, Tadashi
- Venue
- Pediatric Neurology
- Publisher
- Elsevier BV
- Published
- 2019-11
- Volume
- 100
- Pages
- 67-73
- ISSN
- 0887-8994 (ISSN-L)
- PMC
- PMC6755072
- OpenAlex
- W2923678875
- Cited by
- 27
- References
- 36
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 9 · 2021: 5 · 2020: 2 · 2019: 1
- FWCI
- 3.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Pediatric Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- Down syndrome, brain structure, cerebellar gray matter, brainstem volume, cerebellar white matter, cortical abnormalities, comorbidities, infantile spasms, hypothyroidism, infants and toddlers, neuroimaging
- MeSH terms
- Brain, Brain Stem, Child, Preschool, Down Syndrome, Female, Humans, Infant, Magnetic Resonance Imaging, Male, Cohort Studies, Comorbidity, Electronic Health Records, Gray Matter
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