Mowat–Wilson syndrome is a rare

genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...

that was clinically delineated by David R. Mowat and Meredith J. Wilson in 1998. The condition affects both males and females, has been described in various countries and ethnic groups around the world, and occurs in approximately 1 in 50,000-100,000 births.

Presentation

This

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

disorder is characterized by a number of health defects including

Hirschsprung disease Hirschsprung's disease (HD or HSCR) is a birth defect in which nerves are missing from parts of the intestine. The most prominent symptom is constipation. Other symptoms may include vomiting, abdominal pain, diarrhea and slow growth. Symptoms u ...

intellectual disability Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation, Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signif ...

epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrica ...

, delayed growth and motor development, congenital heart disease, genitourinary anomalies and absence of the

corpus callosum The corpus callosum (Latin for "tough body"), also callosal commissure, is a wide, thick nerve tract, consisting of a flat bundle of commissural fibers, beneath the cerebral cortex in the brain. The corpus callosum is only found in placental m ...

. However, Hirschsprung's disease is not present in all infants with Mowat–Wilson syndrome and therefore it is not a required diagnostic criterion.Todo A, Harrington JW
New-onset seizures in infant with square facies, hypospadias, and Hirschsprung disease
Consultant for Pediatricians. 2010;9:103-107. Distinctive physical features include

microcephaly Microcephaly (from New Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it ...

, narrow chin, cupped ears with uplifted lobes with central depression, deep and widely set eyes, open mouth, wide nasal bridge and a shortened

philtrum The philtrum ( la, philtrum from Ancient Greek ''phíltron,'' lit. "love charm"), or medial cleft, is a vertical indentation in the middle area of the upper lip, common to therian mammals, extending in humans from the nasal septum to the tuberc ...

. People with this condition have severe

in almost all cases; however, a small minority have moderate

. Speech is typically limited or absent. Many of those with Mowat–Wilson syndrome also have a distinctive open mouthed, smiling expression and friendly personalities.

Causes

The disorder is expressed in an

fashion and may result from a '' de novo'' loss of function

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, m ...

or total deletion of the ''

ZEB2 Zinc finger E-box-binding homeobox 2 is a protein that in humans is encoded by the ''ZEB2'' gene. The ZEB2 protein is a transcription factor that plays a role in the transforming growth factor β (TGFβ) signaling pathways that are essential durin ...

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

located on

chromosome 2 Chromosome 2 is one of the twenty-three pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 2 is the second-largest human chromosome, spanning more than 242 million base pairs and representing almost e ...

q22.

Diagnosis

Mowat–Wilson syndrome (MWS) can be diagnosed clinically on the basis of moderate to severe

in the presence of characteristic facial features (widely spaced eyes, broad eyebrows with a medial flare, low-hanging columella, prominent or pointed chin, open-mouth expression, and uplifted earlobes with a central depression — coined as orecchiette ears given their resemblance to the pasta). Other clinical features can include

congenital heart defect A congenital heart defect (CHD), also known as a congenital heart anomaly and congenital heart disease, is a defect in the structure of the heart or great vessels that is present at birth. A congenital heart defect is classed as a cardiovascul ...

or chronic constipation, genitourinary anomalies (particularly hypospadias in males), and hypogenesis or agenesis of the corpus callosum. Speech is typically limited to a few words or is absent, with relative preservation of receptive language skills. Growth restriction with microcephaly and seizure disorder are also common. Most affected people have a happy demeanor and a wide-based gait that can sometimes be confused with

Angelman syndrome Angelman syndrome or Angelman's syndrome (AS) is a genetic disorder that mainly affects the nervous system. Symptoms include a small head and a specific facial appearance, severe intellectual disability, developmental disability, limited to no ...

. The diagnosis of MWS confirmed by demonstrating a pathogenic variant (mutation) in the ''

'' gene by molecular genetic testing.

Treatment

To date, there is no cure for MWS. Affected individuals should see a

pediatrician Pediatrics ( also spelled ''paediatrics'' or ''pædiatrics'') is the branch of medicine that involves the medical care of infants, children, adolescents, and young adults. In the United Kingdom, paediatrics covers many of their youth until the ...

or adult physician at least annually to monitor growth, development, seizures and general health and well-being. Developmental potential is maximized through the use of

physiotherapy Physical therapy (PT), also known as physiotherapy, is one of the allied health professions. It is provided by physical therapists who promote, maintain, or restore health through physical examination, diagnosis, management, prognosis, patie ...

occupational therapy Occupational therapy (OT) is a global healthcare profession. It involves the use of assessment and intervention to develop, recover, or maintain the meaningful activities, or ''occupations'', of individuals, groups, or communities. The field of ...

and

speech pathology Speech is a human vocal communication using language Language is a structured system of communication. The structure of a language is its grammar and the free components are its vocabulary. Languages are the primary means by which hum ...

. Medical subspecialist care may be required if other organs are involved (e.g., a

cardiologist Cardiology () is a branch of medicine that deals with disorders of the heart and the cardiovascular system. The field includes medical diagnosis and treatment of congenital heart defects, coronary artery disease, heart failure, valvular ...

and/or

cardiac surgeon Cardiac surgery, or cardiovascular surgery, is surgery on the heart or great vessels performed by cardiac surgeons. It is often used to treat complications of ischemic heart disease (for example, with coronary artery bypass grafting); to corr ...

for

congenital heart disease A congenital heart defect (CHD), also known as a congenital heart anomaly and congenital heart disease, is a defect in the structure of the heart or great vessels that is present at birth. A congenital heart defect is classed as a cardiovascular ...

gastroenterologist Gastroenterology (from the Greek gastḗr- “belly”, -énteron “intestine”, and -logía "study of") is the branch of medicine focused on the digestive system and its disorders. The digestive system consists of the gastrointestinal tract, ...

and or

surgeon In modern medicine, a surgeon is a medical professional who performs surgery. Although there are different traditions in different times and places, a modern surgeon usually is also a licensed physician or received the same medical training as ...

for

Hirschsprung's disease Hirschsprung's disease (HD or HSCR) is a birth defect in which nerves are missing from parts of the intestine. The most prominent symptom is constipation. Other symptoms may include vomiting, abdominal pain, diarrhea and slow growth. Symptoms u ...

constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel moveme ...

Prognosis

There is no cure for this syndrome. Treatment is supportive and symptomatic. All children with Mowat–Wilson syndrome required early intervention with speech therapy, occupational therapy and physical therapy.

References

External links

GeneReview of Mowat–Wilson syndrome
{{DEFAULTSORT:Mowat-Wilson syndrome Transcription factor deficiencies Rare syndromes Rare genetic syndromes Syndromes affecting the gastrointestinal tract Syndromes affecting the heart Syndromes affecting the nervous system Syndromes with intellectual disability Syndromes with craniofacial abnormalities