Neuroimaging findings in Mowat-Wilson syndrome: A study of 54 patients

Livia Garavelli, Ivan Ivanovski, Stefano Giuseppe Caraffi, Daniela Santodirocco, Marzia Pollazzon, Duccio Maria Cordelli, Ebtesam Abdalla, Patrizia Accorsi, Margaret P. Adam, Chiara Baldo, Allan Bayat, Elga Belligni, Federico Bonvicini, Jeroen Breckpot, Bert Callewaert, Guido Cocchi, Goran Cuturilo, Koenraad Devriendt, Mary Beth Dinulos, Olivera DjuricRoberta Epifanio, Francesca Faravelli, Debora Formisano, Lucio Giordano, Marina Grasso, Sabine Grønborg, Alessandro Iodice, Lorenzo Iughetti, Didier Lacombe, Massimo Maggi, Baris Malbora, Isabella Mammi, Sebastien Moutton, Rikke Møller, Petra Muschke, Manuela Napoli, Chiara Pantaleoni, Rosario Pascarella, Alessandro Pellicciari, Maria Luisa Poch-Olive, Federico Raviglione, Francesca Rivieri, Carmela Russo, Salvatore Savasta, Gioacchino Scarano, Angelo Selicorni, Margherita Silengo, Giovanni Sorge, Luigi Tarani, Luis Gonzaga Tone, Annick Toutain, Aurelien Trimouille, Elvis Terci Valera, Samantha Schrier Vergano, Nicoletta Zanotta, Marcella Zollino, William B. Dobyns, Alex R. Paciorkowski

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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 genotype-phenotype 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 neurodevelopment.

Original languageEnglish (US)
Pages (from-to)691-700
Number of pages10
JournalGenetics in Medicine
Volume19
Issue number6
DOIs
StatePublished - Jun 1 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 American College of Medical Genetics and Genomics.

Keywords

  • Mowat-Wilson syndrome
  • ZEB2
  • agenesis of corpus callosum
  • brain MRI
  • genotype-phenotype correlation

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