Mowat-Wilson syndrome is a rare genetic condition impacting multiple parts of the body. First described in 1998, it is characterized by distinct physical traits, developmental delays, and other health concerns apparent at birth or in early childhood. Affecting males and females equally, the syndrome occurs in approximately 1 in 50,000 to 70,000 live births. While features vary among individuals, the cause is a specific genetic alteration.
Genetic Origins of the Syndrome
Mowat-Wilson syndrome (MWS) is caused by a change in the ZEB2 gene. This gene holds instructions for making a protein that is important for the formation of many organs and tissues before birth. In MWS, a mutation or deletion results in an abnormal, nonfunctional protein or a complete loss of the protein from one gene copy. This is known as haploinsufficiency, where one of the two gene copies is not working correctly.
This genetic event is almost always de novo, meaning it is a new change that occurs randomly and is not inherited from a parent. This clarifies for families that the condition is not the result of anything the parents did or did not do. The ZEB2 protein acts as a transcription factor, helping control other genes, so its shortage disrupts multiple developmental processes.
The specific type of mutation—whether it is a small error in the gene’s sequence or a larger deletion—can influence the range and severity of features an individual might have.
Key Physical and Developmental Characteristics
Individuals with Mowat-Wilson syndrome have a recognizable pattern of physical traits, health conditions, and developmental differences. Not every person will have every feature, but a combination is common. The distinct facial appearance often becomes more noticeable as a child gets older.
Distinctive Facial Features
The facial features associated with MWS are distinct. These include widely spaced and deep-set eyes, a broad nasal bridge, and a rounded nasal tip. Eyebrows are often broad with a flare in the middle. Other characteristics are a prominent chin, an open-mouthed expression, and uplifted earlobes that may have a central dimple.
Associated Medical Conditions
Many individuals with MWS are born with other medical conditions.
- Hirschsprung disease, a condition of the large intestine where missing nerve cells make it difficult to pass stool, affects more than half of individuals.
- Congenital heart defects, such as patent ductus arteriosus or problems with pulmonary arteries and valves, are frequently seen.
- Seizures affect a large percentage of individuals, beginning in early childhood.
- Abnormalities of the urinary tract and genitalia, particularly in males, may be present.
- Structural brain differences, like the absence of the tissue connecting the brain’s hemispheres (agenesis of the corpus callosum), can occur.
Chronic constipation is also common in those without a formal Hirschsprung diagnosis.
Developmental Profile
Global developmental delay is a universal feature. Milestones like sitting, standing, and walking are achieved later, with children learning to walk between 4 and 6 years of age with a wide-based gait. The associated intellectual disability ranges from moderate to severe.
Speech is one of the most affected areas. Many individuals are nonverbal or learn to speak only a few words, with language development often delayed. Receptive language skills are often stronger than expressive skills, and many can communicate effectively using methods like sign language. A frequently noted characteristic is a happy and sociable demeanor.
The Diagnostic Process
The diagnostic process for Mowat-Wilson syndrome begins with a clinical evaluation. A physician, often a pediatrician or geneticist, may suspect the syndrome based on its characteristic facial features combined with developmental delays. The presence of specific medical issues, such as Hirschsprung disease or a congenital heart defect, strengthens this clinical suspicion.
While physical and developmental signs are strong indicators, formal diagnostic criteria have not been established. Imaging studies, such as an MRI of the brain or an ultrasound of the heart and kidneys, can help identify associated structural anomalies.
A conclusive diagnosis is made through molecular genetic testing. This involves a blood test to analyze the individual’s DNA for changes in the ZEB2 gene. Testing can identify different types of mutations, and confirming a pathogenic variant in the ZEB2 gene solidifies the diagnosis.
Managing Mowat-Wilson Syndrome
There is no cure for Mowat-Wilson syndrome, so management focuses on addressing symptoms and providing comprehensive support to help individuals reach their full potential. This requires a coordinated, multidisciplinary care team of specialists to address the complex health and developmental needs associated with the condition.
Interventions begin in early childhood and are tailored to each person’s needs. Physical therapy improves motor skills, balance, and coordination, while occupational therapy helps with daily living skills like dressing and feeding. Speech therapy is a primary component of care, often including augmentative and alternative communication (AAC) methods to facilitate communication.
Medical management involves regular monitoring and treatment by specialists. A gastroenterologist manages Hirschsprung disease or chronic constipation, which may require surgery. A cardiologist oversees congenital heart defects, and a neurologist manages seizures with medication. Specialized educational programs and behavioral therapies provide support for learning and social development.