Purpose: Mowat-Wilson syndrome (MWS) is a genetic disease characterized by distinctive facial features, moderate to severe intellectual disability, and congenital malformations, including Hirschsprung disease, genital and eye anomalies, and congenital heart defects, caused by haploinsufficiency of the ZEB2 gene. To date, no characteristic pattern of brain dysmorphology in MWS has been defined. Methods: Through brain magnetic resonance imaging (MRI) analysis, we delineated a neuroimaging phenotype in 54 MWS patients with a proven ZEB2 defect, compared it with the features identified in a thorough review of published cases, and evaluated genotypephenotype correlations. Results: Ninety-six percent of patients had abnormal MRI results. The most common features were anomalies of corpus callosum (79.6% of cases), hippocampal abnormalities (77.8%), enlargement of cerebral ventricles (68.5%), and white matter abnormalities (reduction of thickness 40.7%, localized signal alterations 22.2%). Other consistent findings were large basal ganglia, cortical, and cerebellar malformations. Most features were underrepresented in the literature. We also found ZEB2 variations leading to synthesis of a defective protein to be favorable for psychomotor development and some epilepsy features but also associated with corpus callosum agenesis. Conclusion: This study delineated the spectrum of brain anomalies in MWS and provided new insights into the role of ZEB2 in neuro-development.
Neuroimaging findings in Mowat-Wilson syndrome: a study of 54 patients / Garavelli, Livia; Ivanovski, Ivan; Caraffi, Stefano Giuseppe; Santodirocco, Daniela; Pollazzon, Marzia; Cordelli, Duccio Maria; Abdalla, Ebtesam; Accorsi, Patrizia; Adam, Margaret P; Baldo, Chiara; Bayat, Allan; Belligni, Elga; Bonvicini, Federico; Breckpot, Jeroen; Callewaert, Bert; Cocchi, Guido; Cuturilo, Goran; Devriendt, Koenraad; Dinulos, Mary Beth; Djuric, Olivera; Epifanio, Roberta; Faravelli, Francesca; Formisano, Debora; Giordano, Lucio; Grasso, Marina; Grønborg, Sabine; Iodice, Alessandro; Iughetti, Lorenzo; Lacombe, Didier; Maggi, Massimo; Malbora, Baris; Mammi, Isabella; Moutton, Sebastien; Møller, Rikke; Muschke, Petra; Napoli, Manuela; Pantaleoni, Chiara; Pascarella, Rosario; Pellicciari, Alessandro; Poch Olive, Maria Luisa; Raviglione, Federico; Rivieri, Francesca; Russo, Carmela; Savasta, Salvatore; Scarano, Gioacchino; Selicorni, Angelo; Silengo, Margherita; Sorge, Giovanni; Tarani, Luigi; Tone, Luis Gonzaga; Toutain, Annick; Trimouille, Aurelien; Valera, Elvis Terci; Vergano, Samantha Schrier; Zanotta, Nicoletta; Zollino, Marcella; Dobyns, William B; Paciorkowski, Alex R.. - In: GENETICS IN MEDICINE. - ISSN 1098-3600. - ELETTRONICO. - 19:6(2017), pp. 691-700. [10.1038/gim.2016.176]
Neuroimaging findings in Mowat-Wilson syndrome: a study of 54 patients
TARANI, Luigi;
2017
Abstract
Purpose: Mowat-Wilson syndrome (MWS) is a genetic disease characterized by distinctive facial features, moderate to severe intellectual disability, and congenital malformations, including Hirschsprung disease, genital and eye anomalies, and congenital heart defects, caused by haploinsufficiency of the ZEB2 gene. To date, no characteristic pattern of brain dysmorphology in MWS has been defined. Methods: Through brain magnetic resonance imaging (MRI) analysis, we delineated a neuroimaging phenotype in 54 MWS patients with a proven ZEB2 defect, compared it with the features identified in a thorough review of published cases, and evaluated genotypephenotype correlations. Results: Ninety-six percent of patients had abnormal MRI results. The most common features were anomalies of corpus callosum (79.6% of cases), hippocampal abnormalities (77.8%), enlargement of cerebral ventricles (68.5%), and white matter abnormalities (reduction of thickness 40.7%, localized signal alterations 22.2%). Other consistent findings were large basal ganglia, cortical, and cerebellar malformations. Most features were underrepresented in the literature. We also found ZEB2 variations leading to synthesis of a defective protein to be favorable for psychomotor development and some epilepsy features but also associated with corpus callosum agenesis. Conclusion: This study delineated the spectrum of brain anomalies in MWS and provided new insights into the role of ZEB2 in neuro-development.File | Dimensione | Formato | |
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