Mowat-Wilson Syndrome, a rare genetic condition with intestinal and cerebral symptoms

Mowat Wilson syndrome is a rare genetic condition. Hallmarks are congenital heart defects, urogenital malformations, developmental delay and epileptic seizures. Heterozygous mutations or deletions of the ZEB2 gene, mostly sporadic, are causal for MWS. In about 50% neonatal Hirschsprung disease (HSCR) is an early symptom. Genetics can confirme MWS and induce surveillance and couselling of the patient and its family. We report on a 3 year old girl, first child of healthy unrelated German parents. She was born after an uneventful pregnancy. At her third day of life she presented with ileus and emergency laparatomy was done several times during her first month of life. HSCR was detected via biopsy. Heart defects (ASD, VSD, PDA), a discrete facial phenotype, recognizable ear shapes like red blood cells were present. Molecular genetics was performed showing a well known mutation c.2083C>T, p.R695X in the ZEB2 gene as in Mowat-Wilson-Syndrom. Both parents were negative for that mutation.

Dominant loss of function mutations at the ZEB2 gene are causal for MWS. This gene codes for a Homebox-transcription factor. The gene regulates cell growth and organogenesis. The regulation of the TGF-beta-signal pathway seems to be most relevant in pathogenesis. More than 80% of the patients wear these inactivating mutations/deletions, mostly as de novo mutation, but germ line muatations are prevelant as well. Larger deletions >5Mb predict a more severe clinical phenotype. Our patient has a severe developmental delay, growth retardation, suffers from chronic constipation and has seizures. Treatment is symptomatic. The facial phenotype has become more prominent. The family stays in contact with MWS support group. They have a second child: a healthy daughter.

Mowat Wilson Syndrome - Hirschsprung Disease