Mowat-Wilson syndrome is a genetic disease affecting females twice as often as males [1]. This syndromic illness presents with a variety of clinical manifestations which include a distinctive facies, developmental anomalies, central nervous system, cardiac, gastrointestinal, and genitourinary disorders.

A typical facial appearance is one of the most predominant features seen in Mowat-Wilson syndrome patients, present in up to 98% of affected individuals. Palatal anomalies are seen commonly with cleft palate, bifid uvula, and a high arched palate being the common findings [2]. Some patients present with velopharyngeal insufficiency, micrognathia, glossoptosis, or laryngeal/tracheal abnormalities.

Abnormal growth and development may accompany these features with short stature seen in almost half of affected patients. Microcephaly and delayed gross motor milestones may also be frequently seen.

Amongst the most common central nervous system manifestations of Mowat-Wilson syndrome are focal/absence seizures (seen in 70-75% of patients) and agenesis of the corpus callosum (seen in approximately 50% of patients) [3]. Other less frequent findings include hippocampal dysgenesis, cerebral atrophy, and external hydrocephalus with ventriculomegaly.

Intellectual disability is universally present in patients with Mowat-Wilson syndrome with a large number of individuals having impaired verbal language skills. Repetitive behaviors and antisocial personalities are commonly seen.

Structural congenital heart disorders affecting the pulmonary arteries and/or the valves are seen in a high percentage of cases. Pulmonary artery slings, atrial or ventricular septal defects, coarctation of the aorta, patent ductus arteriosus, and tetralogy of Fallot may be some of the manifestations [4].

Close to half of all patients may suffer from Hirschsprung disease. Pyloric stenosis, chronic constipation, and dysphagia may also occur [5].

Hypospadias and cryptorchidism are some of the frequent genitourinary findings. Other pathologies include hydronephrosis, bifid scrotum, pelvic/duplicated kidney, vesicoureteral reflux, etc.

Strabismus, nystagmus, otitis media, dental anomalies, and pigmentation changes may be seen in a few.

• Short Stature

  Other features include short stature and intellectual disabilities. It is inherited as an autosomal recessive condition. [accessanesthesiology.mhmedical.com]

  stature References Promoted articles (advertising) [radiopaedia.org]

  Patients can show a variety of other anomalies like short stature, microcephaly, Hirschsprung disease, malformations of the brain, seizures, congenital heart defects and urogenital anomalies. [ncbi.nlm.nih.gov]

  Other features of Mowat-Wilson syndrome include short stature, seizures, heart defects, and abnormalities of the urinary tract and genitalia. Less commonly, this condition can also affect the eyes, teeth, hands, and skin coloring (pigmentation). [mowat-wilson.org]

• Abdominal Distension

  Abdominal distension, megacolon, and vomiting are frequent features. Barium enema shows transition zone between aganglionic contracted segment and dilated proximal bowel. [accessanesthesiology.mhmedical.com]

  A 1-day-old girl was referred to the department of surgery for abdominal distension and failure to pass meconium. Targeted exome sequencing revealed a de novo heterozygous nonsense mutation (p.Arg302X) in ZEB2 in the patient. [jhu.pure.elsevier.com]

  A male, 14 months aged patient, son of not consanguineous healthy immigrants parents from Colombia went to the emergency department of our hospital suffering abdominal distension and vomiting with no spontaneous bowels. [ncbi.nlm.nih.gov]

  Shortly after birth, he showed abdominal distension with vomiting. However, rectal biopsy was not performed to confirm a diagnosis of Hirschsprung disease. [labmedonline.org]

  At 20 days the patient had vomiting and abdominal distension; HSCR was diagnosed, and a colostomy was carried out at day 22. [jmg.bmjjournals.com]

• Corneal Opacity

  Other conditions to be considered Mietens-Weber Syndrome: Autosomal recessive disorder characterized by severe mental retardation, corneal opacity, nystagmus, strabismus, small pinched nose, flexion contracture of the elbows, dislocation of head of radius [accessanesthesiology.mhmedical.com]

• Broad Eyebrows

  The distinctive facial features include a high forehead, broad eyebrows, wide spaced eyes, small nose and the prominent pointed chin. The affected children also exhibit the delayed development progress that is slower than average. [mybiosource.com]

  Affected patients show an easily recognizable facial appearance with deep set eyes and hypertelorism, medially divergent, broad eyebrows, prominent columella, pointed chin and uplifted, notched ear lobes. Some patients manifest Hirschsprung disease. [uniprot.org]

  eyebrows, prominent or pointed chin, uplifted earlobes and an opened mouth expression. [dnatesting.uchicago.edu]

  Individuals with this condition have characteristic facial features, including microcephaly, hypertelorism, medially flared and broad eyebrows, prominent columella, pointed chin, and uplifted earlobes, which typically prompt the clinician to consider [ncbi.nlm.nih.gov]

• Sparse to No Eyebrows

  […] hair, sparse eyebrows, telecanthus, low and posteriorly set ears, anteverted nares, short columella, bulbous nasal tip, high-arched palate and short neck. [dovepress.com]

  During early childhood, however, the typical sparse medially flared eyebrows tend to become less obvious, while later on, the prognathism with a “chisel-shaped” chin and the overhanging nasal tip with a low-hanging columella contribute to a rather distinctive [scielo.br]

• Medially Flared Eyebrows

  It is characterized by a distinctive facial appearance, including hypertelorism, sunken eyes, broad nasal bridge, broad and medial flared eyebrows, prominent columella, pointed chin and uplifted earlobes. [scielo.br]

• Muscle Hypotonia

  The presence of hypotonia must be taken into consideration if muscle relaxation is indicated. No pharmacological contraindications are associated with this syndrome. [accessanesthesiology.mhmedical.com]

• Flexion Contracture

  Other conditions to be considered Mietens-Weber Syndrome: Autosomal recessive disorder characterized by severe mental retardation, corneal opacity, nystagmus, strabismus, small pinched nose, flexion contracture of the elbows, dislocation of head of radius [accessanesthesiology.mhmedical.com]

• Short Neck

  […] columella, bulbous nasal tip, high-arched palate and short neck. [dovepress.com]

The diagnosis of Mowat-Wilson syndrome is suspected in patients presenting with the typical clinical features associated with the disease. An atypical presentation is seen only in approximately 2% of individuals and hence, all investigations are geared towards detecting the common anomalies seen in this syndrome (namely the congenital heart diseases, Hirschsprung disease, agenesis of the corpus callosum etc.)

Patterns on electroencephalograms (EEG) are usually unrelated to the structural brain disorders seen in this syndrome with only mild slowing of background activity evident on initial evaluation. Repeat testing may show the characteristic seizure patterns.

All patients suspected of having Mowat-Wilson syndrome must undergo genetic testing of the ZEB2 gene. Sequence analysis of the gene may help detect mutations whilst fluorescence in situ hybridization (FISH) may identify submicroscopic deletions [6] [7]. Polymerase chain reaction (PCR) may enable detection of other genetic abnormalities responsible for this syndrome.

• Multifocal Epileptic Activity

  All the other patients presented with abnormal EEG, including symmetric or asymmetric slowing background activity (in five patients), associated focal epileptic activity (in five patients), multifocal epileptic activity (in one), and generalized epileptic [scielo.br]

• Gliosis

  Subcortical gliosis of the left medial frontal gyrus was also observed in patient 1, and in patient 6, an circumscribed oval lesion was observed, with T1 hypointensity and T2/FLAIR hyperintensity, with intense and homogeneous enhancement, and without [scielo.br]

Treatment The treatment is based on the symptoms evident in each case. In the case of developmental delays with children, the occupational, physical or speech therapy may be useful. [mybiosource.com]

Standard Therapies Treatment The treatment of individuals with MWS should be directed towards the needs of each individual. [rarediseases.org]

You can help by adding to it. ( July 2017 ) Treatment [ edit ] This section is empty. You can help by adding to it. ( July 2017 ) Prognosis [ edit ] There is no cure for this syndrome. Treatment is supportive and symptomatic. [en.wikipedia.org]

The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment. [orpha.net]

The proband was a 15-month-old boy, the youngest of 3 children (2 elder sisters), who was referred to our hospital for the treatment of severe seizures. [ncbi.nlm.nih.gov]

Prognosis Early molecular diagnosis is very practicable today and can be of abundant significance in order to begin the rehabitation and therapeutic treatment as quickly as possible. [syndrome.org]

You can help by adding to it. ( July 2017 ) Prognosis [ edit ] There is no cure for this syndrome. Treatment is supportive and symptomatic. [en.wikipedia.org]

Prognosis Mortality and morbidity depend on the presence and severity of congenital anomalies. Patients have been reported to live into early adulthood but require assistance with the activities of daily living. [orpha.net]

Prognosis There is no cure for this syndrome. Treatment is supportive and symptomatic. [wikidoc.org]

Our studies underscore the importance of genetic contributions in the etiology of infantile hepatobiliary disorders, including biliary atresia. [ncbi.nlm.nih.gov]

Etiology MWS is caused by heterozygous mutations or deletions in the zinc finger E-box-binding homeobox 2 gene, ZEB2, (2q22.3) previously called ZFHX1B (SIP1). [orpha.net]

Recent advances in neuroscience and genetics have greatly expanded our understanding of the brain and of the etiological factors involved in developmental delay and mental retardation. [books.google.de]

Data were compared with those for individuals selected from an epidemiological sample of people with ID from other causes. [ncbi.nlm.nih.gov]

Summary Epidemiology Prevalence is estimated at 1/50,000 to 1/70,000 live births. Over 200 patients have been reported so far. It seems probable that MWS is underdiagnosed, particularly in patients without HSCR. [orpha.net]

An epidemiological study of Wilson’s disease in the Republic of Ireland / M. Reilly, L. Daly, M. Hutchinson // J. Neurol. Neurosurg. Psychiatry. — 1993. — № 56. — Р. 298-300. Brewer G.J. [gastro.zaslavsky.com.ua]

In vitro studies showed that all the three mutations prevented binding and repression of the E-cadherin promoter, a characterized ZEB2 target gene. [ncbi.nlm.nih.gov]

Dramatic gains in 6 out of 7 developmental areas, against the background of a genetic expression trying to prevent that! Not a bad start to the week and another little superstar is born! [snowdrop-snowdropblog.blogspot.com]

Prevention There is still no known prevention for Pierre Robin Syndrome. Treatments are focused on the breathing, feeding, and choking difficulties. [syndromespedia.com]

We propose screening patients with clinical features suggestive of Mowat-Wilson syndrome for asplenia to evaluate the need for additional preventive care. [pediatrics.aappublications.org]

However, preventive measures are identical: NO halogenated agent NOR succinylcholine. [sites.uclouvain.be]

1. Garavelli L, Zollino M, Mainardi PC, et al. Mowat-Wilson syndrome: facial phenotype changing with age: study of 19 Italian patients and review of the literature. Am J Med Genet A. 2009;149A(3):417-426.
2. Mowat DR, Wilson MJ, Goossens M. Mowat-Wilson syndrome. J Med Genet. 2003;40(5):305-310.
3. Cordelli DM, Garavelli L, Savasta S, et al. Epilepsy in Mowat-Wilson syndrome: delineation of the electroclinical phenotype. Am J Med Genet A. 2013;161A(2):273-284.
4. Ishihara N, Yamada K, Yamada Y, et al. Clinical and molecular analysis of Mowat-Wilson syndrome associated with ZFHX1B mutations and deletions at 2q22-q24.1. J Med Genet. 2004;41(5):387-393.
5. Prijoles EJ, Adam M. Mowat-Wilson syndrome with associated dysphagia. Am J Med Genet A. 2010;152A(2):484-485.
6. Zweier C, Albrecht B, Mitulla B, et al. “Mowat-Wilson” syndrome with and without Hirschsprung disease is a distinct, recognizable multiple congenital anomalies-mental retardation syndrome caused by mutations in the zinc finger homeo box 1B gene. Am J Med Genet. 2002;108(3):177-181.
7. Dastot-Le Moal F, Wilson M, Mowat D, Collot N, Niel F, Goossens M. ZFHX1B mutations in patients with Mowat-Wilson syndrome. Hum Mutat. 2007;28(4):313-321.