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Mowat-Wilson Syndrome

Mowat Wilson Syndrome

Mowat-Wilson syndrome is a genetic disorder arising from mutations/deletions in the ZEB2 gene and is manifested by a characteristic facial appearance, growth disorders, and central nervous system anomalies such as mental retardation, seizures, or agenesis of the corpus callosum. Mowat-Wilson syndrome is also associated with other disorders including congenital heart diseases, Hirschsprung disease, and genitourinary abnormalities.


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
  • stature, and genitourinary anomalies.[ncbi.nlm.nih.gov]
  • Congenital anomalies, including Hirschsprung disease (HSCR), congenital heart disease, hypospadias, genitourinary anomalies, agenesis of the corpus callosum, and short stature are common.[ncbi.nlm.nih.gov]
  • 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]
  • It is characterized by a distinctive facial appearance in association with intellectual disability (ID) and variable other features including agenesis of the corpus callosum, seizures, congenital heart defects, microcephaly, short stature, hypotonia,[ncbi.nlm.nih.gov]
Single Transverse Palmar Crease
  • He also presented a high arched palate, penoscrotal hypospadias with penis recurvation (treated surgically at 4 years 5 months), right cryptorchidism, pes planus with calcaneovalgus, mild pectus excavatum, long tapered fingers, single transverse palmar[doi.org]
Abdominal Distension
  • 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]
  • 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]
  • At 20 days the patient had vomiting and abdominal distension; HSCR was diagnosed, and a colostomy was carried out at day 22.[doi.org]
Systolic Murmur
  • Cyanosis and cardiac systolic murmur were present at birth, and echocardiogram showed Fallot’s tetralogy with an absent pulmonary valve. Dysmorphism was observed but the karyotype was normal.[doi.org]
Broad Eyebrows
  • 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]
  • 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]
  • eyebrow Broad eyebrows Flared eyebrow Increased vertical height of eyebrow Increased vertical thickness of eyebrow [ more ] 0011229 Cupped ear Cup-shaped ears Simple, cup-shaped ears [ more ] 0000378 Downslanted palpebral fissures Downward slanting of[rarediseases.info.nih.gov]
Fair Complexion
  • At least two individuals have been described with a fair complexion compared to their family background [ Adam et al 2006 ].[ncbi.nlm.nih.gov]
Behavior Problem
  • Despite this, those with MWS displayed similarly high levels of behavioral problems as those with intellectual disabilities from other causes, with over 30% showing clinically significant levels of behavioral or emotional disturbance.[ncbi.nlm.nih.gov]


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.


  • After resection of the aganglionic colon at the age of 5 months, our patient initially suffered from intermittent constipation, and subsequently by the age of 5 years, he developed ongoing diarrhea requiring medical treatment for more than a decade.[ncbi.nlm.nih.gov]
  • 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]
  • Patient 2 suffered from typical HSCR and underwent surgical treatment, but did not have congenital heart disease. According to the gene analysis using white blood cells, they had nonsense mutations in ZFHX1B, R695X and Q433X, respectively.[ncbi.nlm.nih.gov]
  • Advice on follow-up and treatment Early contact with dental services for intensified prophylactic care and oral hygiene information is essential in cases of difficulty with managing dental treatment and tooth brushing.[mun-h-center.se]


  • 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 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]
  • 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]
  • Herein, we describe two patients who had long histories of unexplained signs and symptoms with a high clinical suspicion of an underlying genetic etiology.[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]
  • Codes: ICD-10: Q43.1 ORPHA: 2152 Estimated occurrence 2:100,000 inhabitants Etiology Mowat-Wilson syndrome normally appears due to a de novo mutation on the ZEB2 gene on chromosome 2q22.3, but can also be due to autosomal dominant inheritance.[mun-h-center.se]


  • 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]
Sex distribution
Age distribution


  • 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]
  • However, preventive measures are identical: NO halogenated agent NOR succinylcholine.[sites.uclouvain.be]
  • Centers for Disease Control and Prevention Intersex (Medical Encyclopedia) [ Read More ] Colonic Diseases Also called: Large intestine diseases Your colon, also known as the large intestine, is part of your digestive system.[icdlist.com]



  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.

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Last updated: 2019-06-28 10:47