Mowat-Wilson syndrome: clinical and molecular report of the first case in mainland China

Mowat-Wilson syndrome (MWS, MIM #235730) is a rare genetic disorder characterized by moderate-tosevere mental retardation, a recognizable facial gestalt and multiple congenital anomalies. The striking facial phenotype in addition to other features such as microcephaly, congenital heart defects, Hirschsprung disease (HSCR), severely delayed motor/speech development, seizures, short stature, corpus callosum agenesis and hypospadias are particularly important clues for the initial clinical diagnosis. All molecularly confirmed cases with typical MWS have a heterozygous loss-of-function mutation in the ZEB2 (zinc finger E-box binding homeobox 2) gene, suggesting that haploinsufficiency of the protein is the main pathological mechanism. Here, we report the first individual with MWS in mainland China confirmed by molecular genetic testing. A 1-day-old girl was referred to the department of surgery for abdominal distension and failure to pass meconium. Targeted exome sequencing revealed a de novo heterozygous nonsense mutation (p.Arg302X) in ZEB2 in the patient. Medical record review revealed mild facial gestalt, HSCR and severe congenital heart defects supporting the diagnosis of MWS. We concluded that facial dysmorphism in newborn babies might be atypical; doctors should pay more attention during physical examination and be aware of MWS if multiple congenital defects were discovered. ZEB2 gene mutation screening would be an effective manner to clarify the diagnosis.