TY - JOUR
T1 - Volumetric Analysis of the Basal Ganglia and Cerebellar Structures in Patients with Phelan-McDermid Syndrome
AU - Developmental Synaptopathies Consortium
AU - Srivastava, Siddharth
AU - Scherrer, Benoit
AU - Prohl, Anna K.
AU - Filip-Dhima, Rajna
AU - Kapur, Kush
AU - Kolevzon, Alexander
AU - Buxbaum, Joseph D.
AU - Berry-Kravis, Elizabeth
AU - Soorya, Latha
AU - Thurm, Audrey
AU - Powell, Craig M.
AU - Bernstein, Jonathan A.
AU - Warfield, Simon K.
AU - Sahin, Mustafa
N1 - Funding Information:
This study is supported by the Developmental Synaptopathies Consortium (U54NS092090), which is a part of the National Center for Advancing Translational Sciences Rare Diseases Clinical Research Network. The Rare Diseases Clinical Research Network is an initiative of the Office of Rare Diseases Research of the National Center for Advancing Translational Sciences, and Developmental Synaptopathies Consortium is funded through collaboration between the National Center for Advancing Translational Sciences, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. We are sincerely indebted to the generosity of the families and patients in PMS clinics across the United States who contributed their time and effort to this study. We would also like to thank the Phelan-McDermid Syndrome Foundation for their continued support in PMS research.
Publisher Copyright:
© 2019
PY - 2019/1
Y1 - 2019/1
N2 - 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.
AB - 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.
KW - 22q13.3 Deletion
KW - Autism
KW - MRI
KW - Repetitive behaviors
KW - SHANK3
UR - http://www.scopus.com/inward/record.url?scp=85055891350&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85055891350&partnerID=8YFLogxK
U2 - 10.1016/j.pediatrneurol.2018.09.008
DO - 10.1016/j.pediatrneurol.2018.09.008
M3 - Article
C2 - 30396833
AN - SCOPUS:85055891350
SN - 0887-8994
VL - 90
SP - 37
EP - 43
JO - Pediatric Neurology
JF - Pediatric Neurology
ER -