From Cortical and Subcortical Grey Matter Abnormalities to Neurobehavioral Phenotype of Angelman Syndrome: A Voxel-Based Morphometry Study.
Angelman syndrome (AS) is a rare neurogenetic disorder due to loss of expression of maternal ubiquitin-protein ligase E3A (UBE3A) gene. It is characterized by severe developmental delay, speech impairment, movement or balance disorder and typical behavioral uniqueness. Affected individuals show normal magnetic resonance imaging (MRI) findings, although mild dysmyelination may be observed. In this study, we adopted a quantitative MRI analysis with voxel-based morphometry (FSL-VBM) method to investigate disease-related changes in the cortical/subcortical grey matter (GM) structures. Since 2006 to 2013 twenty-six AS patients were assessed by our multidisciplinary team. From those, sixteen AS children with confirmed maternal 15q11-q13 deletions (mean age 7.7 ± 3.6 years) and twenty-one age-matched controls were recruited. The developmental delay and motor dysfunction were assessed using Bayley III and Gross Motor Function Measure (GMFM). Principal component analysis (PCA) was applied to the clinical and neuropsychological datasets. High-resolution T1-weighted images were acquired and FSL-VBM approach was applied to investigate differences in the local GM volume and to correlate clinical and neuropsychological changes in the regional distribution of GM. We found bilateral GM volume loss in AS compared to control children in the striatum, limbic structures, insular and orbitofrontal cortices. Voxel-wise correlation analysis with the principal components of the PCA output revealed a strong relationship with GM volume in the superior parietal lobule and precuneus on the left hemisphere. The anatomical distribution of cortical/subcortical GM changes plausibly related to several clinical features of the disease and may provide an important morphological underpinning for clinical and neurobehavioral symptoms in children with AS.
Unit of Neuroradiology, Fondazione CNR/Regione Toscana G. Monasterio, Pisa, Italy.
Gayane
G
Aghakhanyan
Epilepsy and Clinical Neurophysiology Unit, E. Medea Scientific Institute, Conegliano (TV), Italy.
Paolo
P
Bonanni
Epilepsy and Clinical Neurophysiology Unit, E. Medea Scientific Institute, Conegliano (TV), Italy.
Giovanna
G
Randazzo
Epilepsy and Clinical Neurophysiology Unit, E. Medea Scientific Institute, Conegliano (TV), Italy.
Sara
S
Nappi
Epilepsy and Clinical Neurophysiology Unit, E. Medea Scientific Institute, Conegliano (TV), Italy.
Federica
F
Tessarotto
Epilepsy and Clinical Neurophysiology Unit, E. Medea Scientific Institute, Conegliano (TV), Italy.
Lara
L
De Martin
Unit of Neuroradiology, Fondazione CNR/Regione Toscana G. Monasterio, Pisa, Italy.
Francesca
F
Frijia
Unit of Neuroradiology, Fondazione CNR/Regione Toscana G. Monasterio, Pisa, Italy.
Daniele
D
De Marchi
Division of Anesthesiology and Intensive Care, University Hospital of Pisa, Pisa, Italy.
Francesco
F
De Masi
Division of Anesthesiology and Intensive Care, University Hospital of Pisa, Pisa, Italy.
Beate
B
Kuppers
Unit of Neuroradiology, Fondazione CNR/Regione Toscana G. Monasterio, Pisa, Italy.
Francesco
F
Lombardo
Diagnostic and Interventional Radiology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
Davide
D
Caramella
Unit of Neuroradiology, Fondazione CNR/Regione Toscana G. Monasterio, Pisa, Italy.
Domenico
D
Montanaro
D017204:Angelman Syndrome / Q000000981:diagnostic imaging / Q000473:pathology*; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D016022:Case-Control Studies; D002648:Child; D004569:Electroencephalography; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009048:Motor Skills / Q000502:physiology; D059906:Neuroimaging; D009483:Neuropsychological Tests