Mowat-Wilson Syndrome - Symptoms, Diagnosis, and Management

Introduction

Mowat-Wilson syndrome is a genetic disease caused by genetic changes in the ZEB2 gene. The characteristic features of this disorder include distinct facial features, mental retardation, seizures, Hirschsprung disease, and other variable congenital disabilities. Although it is not a common syndrome, it is important to understand and detect it early so that it can be managed and supported in a personalized way. This syndrome has special medical, developmental, and social aspects, so it needs care from different types of doctors and specialists.

What Are the Clinical Features of Mowat-Wilson Syndrome?

Symptoms of this disease start appearing during pregnancy and after birth. Symptoms may also appear in later stages of life.

Distinctive Facial Features

• Square-shaped face.

• High forehead and frontal bossing.

• Deep-set and large eyes.

• Widely spaced eyes (hypertelorism).

• Large and uplifted earlobes with central depression (shaped like red blood corpuscles).

• Saddle nose and a broad nasal bridge.

• Prominent rounded nasal tip.

• The portion between the nostrils (columella) is prominent.

• Open mouth with M-shaped upper lip.

• Frequent smiling.

• A prominent chin that is narrow and triangular pointed.

• Facial features become more apparent as the baby ages.

• In adolescents, the face becomes long with a long pointed chin (prognathism).

What Are the Other Physical and Intellectual Features and Symptoms?

1. Neurologic Findings

• Most people with Mowat-Wilson syndrome have mild to severe intellectual disabilities.

• Delayed development of motor skills.

• Speech is delayed or absent in most cases, with few exceptions.

• Comprehensive ability (understanding what others say) is better than speech. Therefore, children affected by this syndrome learn to communicate through other methods like sign language or communication devices.

• Some patients have a wide-based or ataxic-like gait (insatiable walking).

• Most patients have happy demeanors smiling frequently.

• Happy, friendly, and pleasant personalities are common.

• Seizures of variable nature are present in the majority of the cases.

• Hypoplasia or agenesis of the carpus callosum (brain area connecting two cerebral hemispheres) is seen in about half of the known cases.

• Short stature is common, though some are in normal stature.

• Microcephaly is present in some cases.

2. Hirschsprung Disease

One of the common congenital abnormalities in most cases is Hirschsprung disease. Hirschspruing disease is a gastrointestinal disorder that affects the smooth muscles of the large intestine (colon). Some of the symptoms of Hirschsprung disease include:

• Severe constipation.

• Loss of appetite.

• Vomiting.

• Abdominal bloating or swelling.

• Abnormal accumulation of feces within the colon.

• The Hirschsprung disease may often lead to diarrhea and dehydration, resulting in poor growth and weight gain.

3. Other Clinical Findings

Many other clinical findings are associated with Mowat-Wilson syndrome, but these findings are uncommon in all the known cases.

• Gastrointestinal anomalies like pyloric stenosis.

• Congenital heart defects like patent ductus arteriosus, pulmonary stenosis, and ventricular septal defects.

• Anomalies in the urinary tract and genitalia, such as hypospadias (opening of the urethra on the underside of the penis), cryptorchidism, vesicoureteral reflux, etc.

• Musculoskeletal anomalies - slender build, slender tapering fingers, prominent fingertip pads, pes planus, etc.

• Eye defects like strabismus, astigmatism, and myopia.

• Hearing defects.

• Teeth anomalies like delayed eruptions, crowding, and malpositioned teeth may be seen in some cases.

• Very rarely, skin depigmentation and other skin-related conditions are seen.

What Is the Cause of Mowat-Wilson Syndrome?

Mutations in the ZEB2 gene are the cause of this syndrome. The ZEB2 gene provides instructions for forming a protein important in forming many organs and tissues before birth. When a mutation occurs in a copy of this gene, the protein becomes faulty, absent, or insufficient. Clinical features suggest that the gene is involved in developing the central nervous system, neural crest-derived cells, midline formation, and heart separation. The mutation of the ZEB2 gene usually occurs on its own and is not inherited from the parent.

How Is Mowat-Wilson Syndrome Diagnosed?

Diagnosis is usually made through a thorough clinical evaluation. The characteristic facial feature plays an important role in diagnosing this syndrome. Imaging techniques like CT (computed tomography) scan, MRI (magnetic resonance imaging), and ultrasound of the heart and kidney can be done by doctors to analyze the clinical features of the patient better. The diagnosis can be confirmed by molecular genetic testing to check for mutations.

What Are the Other Conditions That Are Similar to Mowat-Wilson Syndrome?

Symptoms of Mowat-Wilson syndrome overlap with those of other syndromes:

• Goldberg-Shprintzen syndrome is associated with intellectual disability and Hirschsprung disease. This syndrome is due to a mutation in a different gene than Mowat-Wilson syndrome. The facial features also differ between both syndromes.

• Angel man syndrome is often confused with Mowat Wilson syndrome since it shares symptoms like a happy personality, seizures, poor balance, etc. However, some typical congenital abnormalities and facial features distinguish both.

• Smith-Lemli-Opitz syndrome also has many similar clinical features to Mowat-Wilson syndrome.

How Is Mowat-Wilson Syndrome Managed?

• There is no specific treatment for Mowat-Wilson syndrome since the malformations due to the mutated gene occur at the early embryonic stage.

• Treatment depends on the individual’s symptoms and needs.

• The treatment plan is devised according to each individual's clinical findings by a group of different specialists.

• Due to serious congenital malformations, early investigations and interventions by a team of specialists are done.

• Congenital heart disease requires surgery early in life.

• Hirschsprung disease is treated by surgery to relieve bowel obstruction. First, a temporary colostomy is done. Later, surgery is done to remove the affected colon and reattach the healthy parts.

• Physical therapy and occupational therapy are done to treat and improve delayed developmental skills.

• Speech therapy to help overcome speech delays is required.

• Seizures are treated with suitable therapies.

• Surgery is done to correct any genitourinary anomalies if present.

• Other symptoms, like constipation, are treated with appropriate medications.

• Genetic counseling is given to the family members. It involves providing information on the mode of inheritance, nature, and implications of the genetic disorder to help them make medical and personal decisions.

• A periodic follow-up is done regularly to monitor different clinical problems.

What Is the Prognosis for Patients With Mowat-Wilson Syndrome?

There is little information available about the prognosis of patients with Mowat-Wilson syndrome. The oldest patient to be reported so far is 30 years of age. Early molecular diagnosis, available recently, is greatly useful in starting treatment and rehabilitation as early as possible.

Conclusion

Support from the family and caregivers is very crucial for Mowat-Wilson syndrome. Families and caregivers help patients deal with the challenges of this syndrome by giving them support, understanding, and help to find the right resources. Supporting patients with Mowat-Wilson syndrome also contributes to improving their psychomotor development and fostering autonomy. Through ongoing research and awareness efforts, advancements in diagnosis and treatment continue to emerge, for individuals living with Mowat-Wilson Syndrome.