Mowat Wilson syndrome and Hirschsprung disease: a retrospective study on functional outcomes

Pediatr Surg Int. 2020 Nov;36(11):1309-1315. doi: 10.1007/s00383-020-04751-8. Epub 2020 Sep 27.


Aim of the study: Mowat Wilson syndrome (MWS) is a complex genetic disorder due to mutation or deletion of the ZEB2 gene (ZFHX1B), including multiple clinical features. Hirschsprung disease is associated with this syndrome with a prevalence between 43 and 57%. The aim of this study was to demonstrate the severe outcomes and the high complication rates in children with MWS, focusing on their complicated follow-up.

Methods: A retrospective comparative study was conducted on patients referred to Robert-Debré Children's Hospital for MWS from 2003 to 2018. Multidisciplinary follow-up was carried out by surgeons, geneticists, gastroenterologists, and neurologists. Data regarding patient characteristics, surgical management, postoperative complications, and functional outcomes were collected.

Results: Over this period of 15 years, 23 patients were diagnosed with MWS. Hirschsprung disease was associated with 10 of them (43%). Of these cases, two patients had recto-sigmoïd aganglionosis (20%), three had aganglionic segment extension to the left colic angle (30%), two to the right colic angle (20%), and three to the whole colon (30%). The median follow-up was 8.5 years (2 months-15 years). All patients had seizures and intellectual disability. Six children (60%) presented with cardiac defects. At the last follow-up, three patients still had a stoma diversion and 7 (70%) were fed orally. One patient died during the first months. Eight (80%) of these children required a second surgery due to complications. At the last follow-up, three patients reported episodes of abdominal bloating (42%), one recurrent treated constipation (14.3%), and one soiling (14.3%). Genetic analysis identified three patients with heterozygous deletions, three with codon mutations, and three with frameshift mutations.

Conclusions: MWS associated with Hirschsprung disease has a high rate of immediate surgical complications but some patients may achieve bowel function comparable with non-syndromic HD patients. A multidisciplinary follow-up is required for these patients.

Level of evidence: Retrospective observational single cohort study, Level 3.

Publication types

  • Comparative Study
  • Observational Study

MeSH terms

  • DNA Mutational Analysis
  • Defecation / physiology*
  • Digestive System Surgical Procedures / methods*
  • Facies
  • Female
  • Follow-Up Studies
  • Forecasting*
  • Hirschsprung Disease / genetics
  • Hirschsprung Disease / physiopathology*
  • Hirschsprung Disease / surgery
  • Humans
  • Infant, Newborn
  • Intellectual Disability / genetics
  • Intellectual Disability / physiopathology*
  • Intellectual Disability / surgery
  • Male
  • Microcephaly / genetics
  • Microcephaly / physiopathology*
  • Microcephaly / surgery
  • Mutation
  • Retrospective Studies
  • Treatment Outcome
  • Zinc Finger E-box Binding Homeobox 2 / genetics
  • Zinc Finger E-box Binding Homeobox 2 / metabolism
  • Zinc Fingers


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

Supplementary concepts

  • Mowat-Wilson syndrome