Volumetric Analysis of the Basal Ganglia and Cerebellar Structures in Patients with Phelan-McDermid Syndrome
Open accessAbstract
Objective Phelan-McDermid syndrome is caused by haploinsufficiency of SHANK3 on terminal chromosome 22. Knowledge about altered neuroanatomic circuitry in Phelan-McDermid syndrome comes from mouse models showing striatal hypertrophy in the basal ganglia, and from humans with evidence of cerebellar atrophy. To date, no studies have performed volumetric analysis on Phelan-McDermid syndrome patients.Methods We performed volumetric analysis of baseline brain MRIs of Phelan-McDermid syndrome patients (ages three to 21 years) enrolled in a prospective natural history study (ClinicalTrials.gov NCT02461420). Using MRI segmentations carried out with PSTAPLE algorithm, we measured relative volumes (volume of the structure divided by the volume of the brain parenchyma) of basal ganglia and cerebellar structures. We compared these measurements to those of age- and sex-matched healthy controls part of another study. Among the patients, we performed linear regression of each relative volume using Repetitive Behavior Scale-Revised total score and Aberrant Behavior Checklist stereotypy score. Eleven patients with Phelan-McDermid syndrome (six females, five males) and 11 healthy controls were in this analysis.Results At time of MRI, the mean age of the patients and controls was 9.24 (5.29) years and 9.00 (4.49) years, respectively (P = 0.66). Compared to controls, patients had decreased caudate (P ≤ 0.013), putamen (P ≤ 0.026), and left pallidum (P = 0.033) relative volumes. Relative volume of cerebellar vermal lobules I to V (beta coefficient = -17119, P = 0.017) decreased with increasing Repetitive Behavior Scale-Revised total score.Conclusions The volumes of the striatum and left pallidum are decreased in individuals with Phelan-McDermid syndrome. Cerebellar vermis volume may predict repetitive behavior severity in Phelan-McDermid syndrome. These findings warrant further investigation in larger samples.
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Alterations in posterior vermis volume correlate with repetitive behaviors.
“Alterations in posterior vermis volume correlate with repetitive behaviors6,33”
From Regulation of autism-relevant behaviors by cerebellar-prefrontal cortical circuits (2020) · cites this paper as [33]
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- Authors
- Srivastava, S., Scherrer, B., Prohl, A. K., Filip-Dhima, R., Kapur, K., Kolevzon, A., Buxbaum, J. D., Berry-Kravis, E., Soorya, L., Thurm, A., Powell, C. M., Bernstein, J. A., Warfield, S. K., & Sahin, M.
- Affiliations
- Boston Children's Hospital (US)
- Mount Sinai Hospital (US)
- Icahn School of Medicine at Mount Sinai (US)
- Rush University Medical Center (US)
- National Institutes of Health (US)
- The University of Texas Southwestern Medical Center (US)
- Stanford Medicine (US)
- ORCID
- Venue
- Pediatric Neurology
- Publisher
- Elsevier BV
- Published
- 2019-01
- Volume
- 90
- Pages
- 37-43
- ISSN
- 0887-8994 (ISSN-L)
- PMC
- PMC6309632
- OpenAlex
- W2892363427
- Cited by
- 23
- References
- 34
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 4 · 2020: 5 · 2019: 3
- FWCI
- 1.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Pediatric Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Developmental Synaptopathies Consortium (U54NS092090)
- National Center for Advancing Translational Sciences
- National Institute of Mental Health
- National Institute of Neurological Disorders and Stroke
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
- Keywords
- Phelan-McDermid syndrome, basal ganglia, cerebellum, striatal volume, caudate nucleus, putamen, globus pallidus, cerebellar vermis, repetitive behavior, stereotypy, neuroanatomy
- MeSH terms
- Adolescent, Basal Ganglia, Cerebellum, Child, Child, Preschool, Chromosome Deletion, Chromosomes, Human, Pair 22, Female, Humans, Magnetic Resonance Imaging, Male, Organ Size, Chromosome Disorders, Young Adult, Neuroimaging
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