MowatWilson

Mowat-Wilson syndrome (MWS) is a rare autosomal dominant genetic disorder caused by haploinsufficiency of the ZEB2 gene, typically due to de novo pathogenic variants or deletions. It was first described in 1998 by Mowat and Wilson. The condition affects multiple organ systems and is characterized by distinctive facial features, developmental delay, and various congenital anomalies.

Genetically, MWS results from loss of function of ZEB2, a transcription factor that plays a role in the development of neural crest derivatives and other tissues. The disruption of ZEB2 affects diverse body systems, contributing to the syndrome’s wide range of manifestations, including brain, gastrointestinal, and facial features.

Clinical features commonly observed in MWS include a characteristic facial gestalt with features such as a broad nasal bridge and uplifted ear lobes, developmental delay or intellectual disability, and microcephaly in many patients. About half of affected individuals have Hirschsprung disease, a congenital condition of the digestive tract. Brain anomalies, including agenesis or hypoplasia of the corpus callosum, structural abnormalities, and, in some cases, seizures, are also reported. Additional findings may include feeding difficulties, congenital heart defects, growth retardation, and various genital or limb anomalies.

Diagnosis is suggested by clinical presentation and confirmed by genetic testing of ZEB2, using sequencing and deletion analysis to identify pathogenic variants or CNVs. Management requires a multidisciplinary approach, including pediatric genetics, gastroenterology, neurology, developmental therapies, and ongoing medical surveillance. Prognosis varies with the severity of associated anomalies and intellectual disability, but with appropriate support, many individuals achieve meaningful levels of development and quality of life.