Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome 
characterized by a distinct facial phenotype (high forehead, frontal bossing, 
large eyebrows, medially flaring and sparse in the middle part, hypertelorism, 
deep set but large eyes, large and uplifted ear lobes, with a central 
depression, saddle nose with prominent rounded nasal tip, prominent columella, 
open mouth, with M-shaped upper lip, frequent smiling, and a prominent but 
narrow and triangular pointed chin), moderate-to-severe intellectual deficiency, 
epilepsy and variable congenital malformations including Hirschsprung disease 
(HSCR), genitourinary anomalies (in particular hypospadias in males), congenital 
heart defects, agenesis of the corpus callosum and eye anomalies. The prevalence 
of MWS is currently unknown, but 171 patients have been reported so far. It 
seems probable that MWS is under-diagnosed, particularly in patients without 
HSCR. MWS is caused by heterozygous mutations or deletions in the Zinc finger 
E-box-binding homeobox 2 gene, ZEB2, previously called ZFHX1B (SIP1). To date, 
over 100 deletions/mutations have been reported in patients with a typical 
phenotype; they are frequently whole gene deletions or truncating mutations, 
suggesting that haploinsufficiency is the main pathological mechanism. Studies 
of genotype-phenotype analysis show that facial gestalt and delayed psychomotor 
development are constant clinical features, while the frequent and severe 
congenital malformations are variable. In a small number of patients, unusual 
mutations can lead to an atypical phenotype. The facial phenotype is 
particularly important for the initial clinical diagnosis and provides the 
hallmark warranting ZEB2 mutational analysis, even in the absence of HSCR. The 
majority of MWS cases reported so far were sporadic, therefore the recurrence 
risk is low. Nevertheless, rare cases of sibling recurrence have been observed. 
Congenital malformations and seizures require precocious clinical investigation 
with intervention of several specialists (including neonatologists and 
pediatricians). Psychomotor development is delayed in all patients, therefore 
rehabilitation (physical therapy, psychomotor and speech therapy) should be 
started as soon as possible.