Clinical Guidance

ZEB2 deletions and truncating pathogenic variants result in the typical facial features of classic MWS. Deletion sizes and breakpoints vary widely, with no obvious correlation between the phenotype and the size of the deletion, except for individuals with extremely large deletions (5 Mb) that include multiple adjacent genes. In general, those with a whole-gene deletion are more likely to have earlier onset of epilepsy and are at greater risk for epilepsy that is refractory to multiple medications compared to those in whom a defective protein is likely to be produced . Missense, splice site, or in-frame pathogenic variants in ZEB2 represent fewer than 5% of all reported cases and fewer than 2% of those with classic MWS (see also ).

Source: GeneReviews — "Classic Mowat-Wilson Syndrome"

Diagnostic Criteria

Formal clinical diagnostic criteria for classic Mowat-Wilson syndrome (MWS) have not been published. However, the facial features are recognizable and, when accompanied by other features of the condition (e.g., Hirschsprung disease and/or chronic constipation, developmental delay/ intellectual disability), can establish a clinical diagnosis.

Suggestive Findings

Classic MWS should be suspected in individuals with the following clinical and brain MRI findings and family history.

Clinical findings

Source: GeneReviews — "Classic Mowat-Wilson Syndrome"

Differential Diagnosis

Many of the congenital anomalies seen in classic Mowat-Wilson syndrome (MWS) can be seen as isolated anomalies in an otherwise normal individual. Genetic disorders with overlapping features are summarized in . Table 3. Genetic Disorders of Interest in the Differential Diagnosis of Classic Mowat-Wilson Syndrome

Management Guidelines

Clinical management guidelines for Mowat-Wilson syndrome (MWS) have been published (full text).

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs of an individual diagnosed with classic MWS, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 4.

Classic Mowat-Wilson Syndrome: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Constitutional

| Measurement of weight, length/height, head circumference | • To assess for growth restriction microcephaly

• MWS-specific growth charts have been published.1

Eyes | Ophthalmologic eval | To assess for eye anomalies, strabismus, refractive error

Ears | Audiologic eval | To assess for hearing loss

Mouth

| Dental eval | Early in childhood, typically starting at age ~3 yrs

Cardiovascular

| EKG echocardiogram, ideally w/cardiologist consultation | To assess for structural heart defects

Gastrointestinal

| Assessment for signs symptoms of dysphagia | Consider VFSS for those w/suggestive features.

Assessment for history of chronic constipation | • Referral to GI specialist for eval of possible HSCR /or primary gut motility issues

• Treatment of chronic constipation may improve rates of urinary incontinence.

Genitourinary

| Abdominal ultrasound | To assess for structural renal anomalies presence of a spleen

Assessment for hypospadias /or cryptorchidism in males | Consider referral to urologist.

Source: GeneReviews — "Classic Mowat-Wilson Syndrome"

Clinical Guidance

At least one individual with tantrums and difficulties focusing had worsening aggression after a trial of stimulant medication . Stimulant medication should be used with caution in individuals with classic MWS.

Source: GeneReviews — "Classic Mowat-Wilson Syndrome"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Classic Mowat-Wilson Syndrome"

Surveillance Guidelines

The specific features present in any given individual typically guide surveillance. Follow up with a cardiologist, gastroenterologist, neurologist, urologist, and developmental pediatrician as clinically indicated is recommended. In addition, the evaluations summarized in should be considered. Table 6. Classic Mowat-Wilson Syndrome: Recommended Surveillance

Source: GeneReviews — "Classic Mowat-Wilson Syndrome"