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

Genet Med. 2017 Jun;19(6):691-700. doi: 10.1038/gim.2016.176. Epub 2016 Nov 10.

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.Genet Med advance online publication 10 November 2016.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / diagnostic imaging*
  • Brain / pathology
  • Child
  • Child, Preschool
  • Cohort Studies
  • Epilepsy / pathology
  • Facies
  • Female
  • Genotype
  • Haploinsufficiency
  • Hirschsprung Disease / diagnostic imaging*
  • Hirschsprung Disease / genetics
  • Hirschsprung Disease / pathology
  • Humans
  • Infant
  • Intellectual Disability / diagnostic imaging*
  • Intellectual Disability / genetics
  • Intellectual Disability / pathology
  • Longitudinal Studies
  • Magnetic Resonance Imaging*
  • Male
  • Microcephaly / diagnostic imaging*
  • Microcephaly / genetics
  • Microcephaly / pathology
  • Neuroimaging*
  • Phenotype
  • Zinc Finger E-box Binding Homeobox 2 / genetics

Substances

  • ZEB2 protein, human
  • Zinc Finger E-box Binding Homeobox 2

Supplementary concepts

  • Mowat-Wilson syndrome