MOWAT-WILSON SYNDROME
ALSO KNOWN AS
• MWS
• MICROCEPHALY, MENTAL RETARDATION, AND DISTINCT FACIAL
FEATURES, WITH OR WITHOUT HIRSCHSPRUNG DISEASE
• HIRSCHSPRUNG DISEASE SYNDROME
• HIRSCHSPRUNG DISEASE-MENTAL RETARDATION SYNDROME
GENERAL INFORMATION ABOUT MOWAT-WILSON
SYNDROME
Mowat-Wilson syndrome is a rare genetic condition that may be evident at
birth (congenital) or during infancy. Some cases may not be recognised
until childhood or adulthood especially when Hirschsprung disease is not
present.
The major symptoms include intellectual disability, distinctive facial
characteristics and seizures. Additional features may include
Hirschsprung disease (disorder of the colon), microcephaly (smaller than
normal head size), congenital heart disease, male genital abnormalities,
kidney anomalies and short stature.
Mowat-Wilson syndrome results from new genetic changes (mutations) in
the ZFHX1B gene located on chromosome 2.
Mowat-Wilson syndrome is characterised by the following facial features:
• Square shaped face (infancy)
• Long face (adolescence)
• Prominent but narrow triangular chin
• Hypertelorism (wide set eyes)
• Deep set but large eyes
• Broad nasal bridge
• Prominent rounded nasal tip
• Open mouth
• High arched palate
• Full or everted lower lip
• Medially sparse broad eyebrows
• Uplifted ear lobes with a central depression
Moderate to severe intellectual disability is usual. Most people with
Mowat-Wilson syndrome have a happy demeanour with frequent smiling. Speech is
often very delayed or absent although comprehension is usually much better. Some
children communicate well using signing techniques.
Motor milestones are always very delayed. Most children cruise for longer than
expected before walking independently. Seizures are common, occurring in
approximately 90% of individuals by 10 years of age. Seizures can be difficult
to control in childhood but are not usually a major problem in adults. Cerebral
imaging (MRI or CT) sometimes demonstrates absence of the corpus callosum, a
structure connecting the two hemispheres of the brain or smaller brain size
(especially frontal lobes).
Short stature is usual although some people have normal stature.
Hirschsprung disease has been present in approximately 60% of individuals
diagnosed so far.
Hirschsprung disease (HSCR) is a rare condition of the colon usually diagnosed
soon after birth with symptoms of bowel obstruction or severe constipation.
Milder forms of HSCR might not be diagnosed in infancy. A history of significant
constipation warrants investigation for possible mild HSCR (rectal biopsy).
Additional features may include congenital heart disease, problems with the
development of the kidneys and/or the male genitalia, ptosis (droopy eyelids),
strabismus (crossed eyes), pigmented spots in the iris, calcaneovalgus (foot
position alteration, a bit similar to flat feet), slender fingers and toes, and
rarely cleft palate.
IS THERE ANY TREATMENT FOR MOWAT-WILSON SYNDROME?
Mowat-Wilson syndrome is usually diagnosed during infancy or childhood, based upon a thorough clinical evaluation, identification of characteristic physical findings and facial appearance, and information from a variety of specialised tests. Such testing may include imaging techniques, such as computerised tomography (CT) scanning or magnetic resonance imaging (MRI) of the brain.
Standard chromosome testing is usually normal in MWS. The clinical diagnosis can
be confirmed by DNA testing or FISH directed at the ZFHX1B gene. As MWS is rare,
all children with suspected
MWS should be referred to a clinical geneticist, who will be able to organise
the specialised testing if necessary.
Treatment.
The treatment of Mowat-Wilson
syndrome is directed toward the specific symptoms that are apparent in each
individual. Such treatment may require the coordinated efforts of a team of
medical professionals.
In some cases seizures have been resistant to treatment in childhood, but appear
to be more easily managed in adolescents and adults.
Treatment of Hirschsprung disease usually consists of surgery to relieve bowel
obstruction. A temporary bowel opening of the colon in the abdominal wall
(colostomy) is usually performed. A second operation is performed later to
remove the non-functioning section of the colon, and rejoin the healthy sections
of bowel.
It is important to distinguish this condition from other similar syndromes that
may have a different mode of inheritance. Since Mowat-Wilson syndrome occurs
sporadically, the recurrence risk is low. To help understand this, families may
benefit from genetic counselling.
Mowat-Wilson syndrome usually occurs as a result of new genetic changes in a gene called zinc finger homeobox 1B (ZFHX1B), which is located on chromosome 2 in the region known as 2q22.
These changes lead to loss of function of one copy of the gene. The genetic
change causing MWS is almost always sporadic, meaning that in nearly all cases,
the genetic change has occurred at the time of formation of the egg or sperm for
that child only, and no other family member will be
affected. Gene testing is available on a limited basis at present, but can be
useful to confirm the diagnosis and to aid in genetic counselling.
MWS is distinguished from other syndromic forms of HSCR by the characteristic
facial
appearance. One such form of syndromic HSCR is called Goldberg-Shprintzen
syndrome (GSS). In GSS the facial features are different and there may be
additional features such as coloboma of the iris or retina. GSS is thought to be
inherited in an autosomal recessive manner, as in reported cases, there have
been some recurrences within families and a higher proportion of consanguinity
(related parents) than expected. The chromosome locus, or the gene, causing GSS
has not been identified. Mutations in the ZFHX1B gene have not yet been found in
children with GSS.
Some MWS children have been thought to have Angelman syndrome because both
conditions share features such as a happy personality, microcephaly, seizures
and poor balance. The facial appearance is quite different in Angelman syndrome,
and an experienced clinical geneticist should
be able to recognise the difference.
Who is affected?
Mowat-Wilson syndrome has been identified in
more males than females so far. This is probably because the initial cases were
identified because of the presence of HSCR and HSCR is more
common in males. In cases identified because of the facial features and
intellectual disability the ratio of males to females is 1:1.
This syndrome was first recognised as a distinct cause of syndromic HSCR in
1998. The gene involved, ZFHX1B (previously called SIP1) was identified in 2001.
Since then there have been more than 100 confirmed cases with mutations within
the ZFHX1B gene reported in the literature.
As this is a newly described condition it is likely that many more cases will be
recognised over the next few years. MWS may be responsible for up to 50% of
syndromic HSCR. The exact incidence
of MWS is unknown, although it is likely to be a rare condition (less than 1 in
20,000). Cases without HSCR are more difficult to recognise unless the doctor is
familiar with the characteristic facial features of MWS.
Source
The Centre for
Genetics Education, a branch of
the NSW Genetics Service.
Disclaimer
Please note that the information contained within this page are not intended to be used as a diagnosis. If you suspect that you have a child with MWS you should consult your doctor. Whilst we have made every effort to ensure the information is accurate, we will not assume any responsibility for any errors.