Neuropathology of Mowat-Wilson Syndrome

Pediatr Dev Pathol. 2020 Aug;23(4):322-325. doi: 10.1177/1093526620903956. Epub 2020 Apr 6.

Abstract

Mowat-Wilson syndrome (MWS) is a syndromic form of Hirschsprung disease that is characterized by variable degrees of intellectual disability, characteristic facial dysmorphism, and a diverse set of other congenital malformations due to haploinsufficiency of ZEB2. A variety of brain malformations have been described in neuroimaging studies of MWS patients, and the role of ZEB2 in the brain has been studied in a multitude of genetically engineered mouse models that are now available. However, a paucity of autopsy information limits our ability to correlate data from neuroimaging studies and animal models with actual MWS patient tissues. Here, we report the autopsy neuropathology of a 19-year-old male patient with MWS. Autopsy neuropathology findings correlated well with the reported MWS neuroimaging data and are in keeping with data from genetically engineered MWS mouse models. This autopsy enhances our understanding of ZEB2 function in human brain development and demonstrates the reliability of MWS murine models.

Keywords: Mowat–Wilson syndrome; ZEB2; autopsy; microcephaly; neuropathology.

Publication types

  • Case Reports

MeSH terms

  • Autopsy
  • Biomarkers / metabolism
  • Brain / metabolism
  • Brain / pathology*
  • Facies
  • Fatal Outcome
  • Hirschsprung Disease / diagnosis
  • Hirschsprung Disease / genetics
  • Hirschsprung Disease / metabolism
  • Hirschsprung Disease / pathology*
  • Humans
  • Intellectual Disability / diagnosis
  • Intellectual Disability / genetics
  • Intellectual Disability / metabolism
  • Intellectual Disability / pathology*
  • Male
  • Microcephaly / diagnosis
  • Microcephaly / genetics
  • Microcephaly / metabolism
  • Microcephaly / pathology*
  • Young Adult
  • Zinc Finger E-box Binding Homeobox 2 / genetics
  • Zinc Finger E-box Binding Homeobox 2 / metabolism

Substances

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

Supplementary concepts

  • Mowat-Wilson syndrome