Mowat-Wilson syndrome is a genetic disease affecting females twice as often as males [1]. This syndromic illness presents with a variety of clinical manifestations which include a distinctive facies, developmental anomalies, central nervous system, cardiac, gastrointestinal, and genitourinary disorders.

A typical facial appearance is one of the most predominant features seen in Mowat-Wilson syndrome patients, present in up to 98% of affected individuals. Palatal anomalies are seen commonly with cleft palate, bifid uvula, and a high arched palate being the common findings [2]. Some patients present with velopharyngeal insufficiency, micrognathia, glossoptosis, or laryngeal/tracheal abnormalities.

Abnormal growth and development may accompany these features with short stature seen in almost half of affected patients. Microcephaly and delayed gross motor milestones may also be frequently seen.

Amongst the most common central nervous system manifestations of Mowat-Wilson syndrome are focal/absence seizures (seen in 70-75% of patients) and agenesis of the corpus callosum (seen in approximately 50% of patients) [3]. Other less frequent findings include hippocampal dysgenesis, cerebral atrophy, and external hydrocephalus with ventriculomegaly.

Intellectual disability is universally present in patients with Mowat-Wilson syndrome with a large number of individuals having impaired verbal language skills. Repetitive behaviors and antisocial personalities are commonly seen.

Structural congenital heart disorders affecting the pulmonary arteries and/or the valves are seen in a high percentage of cases. Pulmonary artery slings, atrial or ventricular septal defects, coarctation of the aorta, patent ductus arteriosus, and tetralogy of Fallot may be some of the manifestations [4].

Close to half of all patients may suffer from Hirschsprung disease. Pyloric stenosis, chronic constipation, and dysphagia may also occur [5].

Hypospadias and cryptorchidism are some of the frequent genitourinary findings. Other pathologies include hydronephrosis, bifid scrotum, pelvic/duplicated kidney, vesicoureteral reflux, etc.

Strabismus, nystagmus, otitis media, dental anomalies, and pigmentation changes may be seen in a few.

The diagnosis of Mowat-Wilson syndrome is suspected in patients presenting with the typical clinical features associated with the disease. An atypical presentation is seen only in approximately 2% of individuals and hence, all investigations are geared towards detecting the common anomalies seen in this syndrome (namely the congenital heart diseases, Hirschsprung disease, agenesis of the corpus callosum etc.)

Patterns on electroencephalograms (EEG) are usually unrelated to the structural brain disorders seen in this syndrome with only mild slowing of background activity evident on initial evaluation. Repeat testing may show the characteristic seizure patterns.

All patients suspected of having Mowat-Wilson syndrome must undergo genetic testing of the ZEB2 gene. Sequence analysis of the gene may help detect mutations whilst fluorescence in situ hybridization (FISH) may identify submicroscopic deletions [6] [7]. Polymerase chain reaction (PCR) may enable detection of other genetic abnormalities responsible for this syndrome.

There is no cure for Mowat-Wilson Syndrome, but treatment focuses on managing symptoms and improving quality of life. A multidisciplinary approach is often necessary, involving specialists such as neurologists, cardiologists, and speech therapists. Interventions may include physical therapy, speech therapy, and medications to control seizures. Surgical procedures might be required to address congenital anomalies like heart defects or Hirschsprung disease.

The prognosis for individuals with Mowat-Wilson Syndrome varies depending on the severity of symptoms and associated health issues. While intellectual disability and developmental delays are common, many individuals can achieve a good quality of life with appropriate support and interventions. Lifespan may be affected by the presence of severe congenital anomalies or complications from associated conditions.

Mowat-Wilson Syndrome is caused by mutations in the ZEB2 gene, which is located on chromosome 2. This gene is responsible for producing a protein that regulates the development of various tissues and organs. Mutations in ZEB2 disrupt normal development, leading to the characteristic features and symptoms of the syndrome. Most cases occur sporadically, meaning they are not inherited from parents.

Mowat-Wilson Syndrome is considered a rare disorder, with an estimated prevalence of 1 in 50,000 to 1 in 70,000 individuals. It affects both males and females equally and has been reported in various ethnic groups worldwide. Due to its rarity, MWS may be underdiagnosed or misdiagnosed, especially in individuals with milder symptoms.

The pathophysiology of Mowat-Wilson Syndrome involves the disruption of normal developmental processes due to mutations in the ZEB2 gene. This gene plays a critical role in the formation of neural crest cells, which contribute to the development of facial features, the nervous system, and other structures. The absence or malfunction of the ZEB2 protein leads to the diverse range of symptoms seen in MWS.

Currently, there are no known methods to prevent Mowat-Wilson Syndrome, as it is a genetic condition resulting from spontaneous mutations. Genetic counseling may be beneficial for families with a history of the syndrome or those who have a child diagnosed with MWS, to understand the risks and implications for future pregnancies.

Mowat-Wilson Syndrome is a rare genetic disorder caused by mutations in the ZEB2 gene, leading to distinctive facial features, intellectual disability, and various congenital anomalies. Diagnosis involves clinical evaluation and genetic testing, while treatment focuses on managing symptoms through a multidisciplinary approach. Although there is no cure, individuals with MWS can achieve a good quality of life with appropriate support.

For patients and families affected by Mowat-Wilson Syndrome, understanding the condition is crucial. MWS is a genetic disorder that affects development, leading to unique facial features, intellectual challenges, and other health issues. While there is no cure, many treatments and therapies can help manage symptoms and improve quality of life. Support from healthcare professionals, educators, and support groups can be invaluable in navigating the challenges associated with MWS.

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