Mowat-Wilson Syndrome · What It Is, Causes, Signs and Symptoms, Diagnosis, and More

The signs and symptoms of Mowat-Wilson syndrome include a wide array of structural malformations. Distinctive facial features include a high forehead, microcephaly (i.e., small head), hypertelorism (i.e., wide space between eyes), pointed triangular chin, prominent round nasal tip (i.e., columella), dental crowding, and an open mouth. 

Individuals with Mowat-Wilson syndrome can have diminished development of or agenesis of the corpus callosum (i.e., fibers connecting two hemispheres of the brain), malformation of the hippocampus, reduced white matter, craniosynostosis, and cortical dysgenesis. A multitude of neurologic abnormalities can result, which include epilepsy, severe intellectual disabilities (e.g., autistic qualities, attention deficit disorder), sleep disturbance, bruxism, and impaired speech. Affected individuals may also display a happy demeanor, which can cause this disorder to be mistaken for Angelman syndrome. Poor eyesight can also occur due to eye abnormalities (e.g., strabismus, refractive errors). Sleep disturbances such as night wakings and early morning wakings are also common. 

Enteric complications are a result of Hirschsprung disease (e.g., a congenital condition affecting nerve cells in the colon), which may cause delayed passage of meconium as a neonate and chronic constipation, while the skeletal abnormalities seen (e.g., scoliosis, foot deformities) can cause discomfort and gait changes. Congenital heart disease (e.g., patent ductus arteriosus, ventricular septal defect, atrial septal defect, pulmonary stenosis, and coarctation of the aorta) can lead to fatigue, tachycardia (i.e., elevated heart rate), and difficulty breathing. Genitourinary anomalies (e.g., hypospadias, cryptorchidism, hydronephrosis, vesicoureteral reflux) are also common.

Mowat-Wilson syndrome can be diagnosed after a thorough medical and physical exam and confirmatory genetic testing. Although no formal diagnostic criteria are outlined, the distinctive characteristics may lead healthcare professionals to a clinical diagnosis. The pattern includes dysmorphic facial features, developmental delay, moderate to severe intellectual disabilities, impaired speech, epilepsy, and eye abnormalities. If all, or most, of these conditions, are present then there may be high suspicion of Mowat-Wilson syndrome.  Imaging studies (e.g., CT, MRI) may show neurological abnormalities.  

In addition to clinical findings, diagnosis of MWS is reliant on genetic analysis. If there is a high suspicion of Mowat-Wilson syndrome, gene-targeted testing, which analyzes the ZEB2 gene individually, can be performed. Other broader genetic testing may also be completed to assess for other syndromes.