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, 19 (6), 691-700

Neuroimaging Findings in Mowat-Wilson Syndrome: A Study of 54 Patients

Livia Garavelli  1 Ivan Ivanovski  1   2 Stefano Giuseppe Caraffi  3 Daniela Santodirocco  1 Marzia Pollazzon  1 Duccio Maria Cordelli  4 Ebtesam Abdalla  5   6 Patrizia Accorsi  7 Margaret P Adam  8 Chiara Baldo  9 Allan Bayat  10   11 Elga Belligni  12 Federico Bonvicini  1   13 Jeroen Breckpot  14 Bert Callewaert  15 Guido Cocchi  16 Goran Cuturilo  17   18 Koenraad Devriendt  14 Mary Beth Dinulos  19 Olivera Djuric  1 Roberta Epifanio  20 Francesca Faravelli  21 Debora Formisano  22 Lucio Giordano  7 Marina Grasso  9 Sabine Grønborg  23 Alessandro Iodice  24 Lorenzo Iughetti  13 Didier Lacombe  25   26 Massimo Maggi  27 Baris Malbora  28 Isabella Mammi  29 Sebastien Moutton  25   30 Rikke Møller  31   32 Petra Muschke  33 Manuela Napoli  27 Chiara Pantaleoni  34 Rosario Pascarella  27 Alessandro Pellicciari  4 Maria Luisa Poch-Olive  35 Federico Raviglione  36 Francesca Rivieri  37 Carmela Russo  27 Salvatore Savasta  38 Gioacchino Scarano  39 Angelo Selicorni  40   41 Margherita Silengo  12 Giovanni Sorge  42 Luigi Tarani  43 Luis Gonzaga Tone  44 Annick Toutain  45 Aurelien Trimouille  25 Elvis Terci Valera  44 Samantha Schrier Vergano  46   47 Nicoletta Zanotta  20 Marcella Zollino  48 William B Dobyns  49   50 Alex R Paciorkowski  51   52   53   54

Neuroimaging Findings in Mowat-Wilson Syndrome: A Study of 54 Patients

Livia Garavelli et al. Genet Med.


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.Genet Med advance online publication 10 November 2016.


Figure 1
Figure 1
Brain magnetic resonance imaging findings in the cohort and in the literature.
Figure 2
Figure 2
Brain magnetic resonance imaging findings in the cohort. (a) Complete agenesis of corpus callosum; (b) partial agenesis of corpus callosum; (c) hypoplasia of corpus callosum; (d) hippocampal abnormalities; (e) lateral ventricle enlargement and reduction of white matter thickness; (f) localized signal alteration of white matter; (g) cortical dysplasia; (h) ventricular temporal horn enlargement; (i) large basal ganglia; (j) posterior fossa findings; and (k) periventricular nodular heterotopia.
Figure 3
Figure 3
Genotype–phenotype correlation. (a) Brain magnetic resonance imaging features; (b) seizure onset; (c) types of seizures and resistance to therapy; and (d) developmental milestones.

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