Mowat-Wilson syndrome

Mowat-Wilson syndrome is a multisystem genetic condition that combines distinctive facial features with significant developmental and neurological challenges as well as a range of congenital malformations. The disorder is caused by pathogenic variants in the ZEB2 gene, which is important for orchestrating early organ and tissue development. Signs usually emerge in infancy or early childhood when delays in growth, speech, and bowel function prompt medical evaluation. Although exact numbers are not available, the syndrome is considered uncommon worldwide, affecting both males and females. Because many body systems can be involved, care typically requires coordination among several medical specialists.

The facial appearance is often the first clue for clinicians. A low-hanging columella (the tissue between the nostrils), widely spaced eyes, and an open-mouth expression create a recognizable look shared by most children with the syndrome. Nearly all affected individuals have severe intellectual disability accompanied by markedly delayed or absent speech, reflecting the condition’s significant cognitive and developmental impact. Early in life, prolonged constipation or intestinal blockage may occur because a substantial proportion of children develop Hirschsprung disease, a form of aganglionic megacolon that requires surgical management. Seizures and low muscle tone (hypotonia) are frequent neurological findings, and magnetic resonance imaging may reveal abnormalities of the corpus callosum or other white-matter structures. Growth can be slowed, leading to short stature and microcephaly in many but not all individuals. Other body systems can also be affected. Genitourinary anomalies such as hypospadias or undescended testes are common in males. Heart defects, kidney malformations, recurrent ear infections, strabismus, and dental issues such as tooth malposition or delayed eruption contribute to the broad clinical spectrum. Not all individuals experience all features, and severity varies considerably from person to person.

Mowat-Wilson syndrome is inherited in an autosomal dominant pattern, meaning that a single altered copy of the ZEB2 gene can lead to the condition. In this inheritance model, each child of an affected individual has a 50% chance of inheriting the pathogenic variant. The ZEB2 protein helps regulate how other genes are switched on or off during embryonic development, so changes in ZEB2 can disrupt the formation of multiple organs and brain structures. Families who receive this diagnosis are encouraged to meet with a genetic counselor to discuss testing of relatives, family-planning options, and the variable ways the condition may appear in different family members (variable expressivity).

Currently, management focuses on supportive care and symptom management. Treatment is tailored to the individual and typically involves a multidisciplinary team that may include neurologists, gastroenterologists, surgeons, cardiologists, developmental pediatricians, and therapists. Early-intervention services such as speech, occupational, and physical therapies aim to maximize developmental potential and improve daily functioning. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Examples include growth monitoring, neurologic evaluations for seizure control, hearing assessments for recurrent ear infections, and periodic cardiac or renal imaging when congenital anomalies are present. Families should discuss with their care team which specialists to see and how often. Because no targeted or gene-specific therapies are yet approved, participation in registries or clinical trials may provide access to emerging interventions as research advances.

Outcomes for individuals with Mowat-Wilson syndrome depend on the combination and severity of congenital anomalies, seizure control, and access to comprehensive support services. Many children require lifelong assistance with daily activities and communication, yet with coordinated care they can achieve meaningful developmental gains and enjoy a good quality of life within their abilities. Severity and symptoms vary widely between individuals, making it difficult to predict any single course. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with expert centers, patient support groups, and genetic counselors to stay informed about emerging therapies and to navigate educational and social resources.

Clinical trials are underway exploring new treatment approaches and natural-history studies for Mowat-Wilson syndrome. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.