Mowat-Wilson syndrome

Mowat-Wilson syndrome (MWS), also known as Mowat-Wilson syndrome due to ZEB2 deficiency or Hirschsprung disease–intellectual disability syndrome, is a rare genetic neurodevelopmental disorder caused by heterozygous loss-of-function mutations or deletions of the ZEB2 (also known as SIP1 or ZFHX1B) gene on chromosome 2q22. The condition affects multiple body systems and is characterized by a distinctive facial appearance (widely spaced eyes, broad nasal bridge, prominent rounded nasal tip, open mouth with M-shaped upper lip, and uplifted earlobes), moderate to severe intellectual disability, delayed motor development, and limited or absent speech. Seizures (epilepsy) occur in the majority of affected individuals, typically presenting in early childhood. Hirschsprung disease (aganglionosis of the colon) is a hallmark feature, present in approximately 50–60% of individuals with MWS, and is often the presenting clinical finding that leads to diagnosis. Other frequently associated anomalies include congenital heart defects (such as patent ductus arteriosus, ventricular septal defect, and pulmonary artery sling), urogenital anomalies (hypospadias, cryptorchidism, renal malformations), eye abnormalities (microphthalmia, coloboma, strabismus), and structural brain anomalies including agenesis or hypoplasia of the corpus callosum. Growth may be affected, with short stature observed in some patients. Individuals with MWS typically have a happy and sociable demeanor. There is no cure for Mowat-Wilson syndrome, and management is supportive and symptom-directed. Hirschsprung disease requires surgical intervention (pull-through procedure). Epilepsy is managed with antiepileptic medications, and congenital heart defects may require surgical correction. Speech therapy, physical therapy, occupational therapy, and special educational support are essential components of long-term care. Regular monitoring by a multidisciplinary team including neurology, cardiology, gastroenterology, urology, and ophthalmology is recommended.

Common questions about Mowat-Wilson syndrome