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]

  stature, and genitourinary anomalies. [ncbi.nlm.nih.gov]

  The striking facial phenotype in addition to other features such as microcephaly, congenital heart defects, Hirschsprung disease (HSCR), severely delayed motor/speech development, seizures, short stature, corpus callosum agenesis and hypospadias are particularly [jhu.pure.elsevier.com]

• Lymphedema

  […] syndrome ) · PAX3 ( Waardenburg syndrome 1&3 ) · PAX4 ( MODY 9 ) · PAX6 (Gillespie syndrome, Coloboma of optic nerve ) · PAX8 ( Congenital hypothyroidism 2 ) · PAX9 ( STHAG3 ) 3.3: FOXC1 ( Axenfeld syndrome 3, Iridogoniodysgenesis, dominant type ) · FOXC2 (Lymphedema–distichiasis [enacademic.com]

  MT-TF, MT-ND5, MT-TK, MITO Melnick-Needles-Syndrom FLNA, Merosin-deficient CMD LAMA2 Metachromatische Leukodystrophie ARSA Metaphyseal chondrodysplasia, Schmid type COL10A1 Microcephaly ASPM, SLC25A19, CEP152 MIDAS-Syndrom HCCS, HCCS Milroy Disease/Lymphedema-Dystichiasis [meduniwien.ac.at]

  Germline CBL mutation associated with a noonan-like syndrome with primary lymphedema and teratoma associated with acquired uniparental isodisomy of chromosome 11q23. American Journal of Medical Genetics, Part A, 164A (4), 1003-1009. [sydney.edu.au]

• Dysostosis

  Li-Fraumeni syndrome · Ulnar–mammary syndrome 4.7: Campomelic dysplasia · MODY 3 · MODY 5 · SF1 (SRY XY gonadal dysgenesis, Premature ovarian failure 7 ) · SOX10 ( Waardenburg syndrome 4c, Yemenite deaf-blind hypopigmentation syndrome) 4.11: Cleidocranial dysostosis [enacademic.com]

  Spermatogenic failure 4 SYCP3 spinal muscular atrophy with respiratory distress (SMARD1) IGHMBP2 Spinale Muskelatrophie (SMA) SMN1 Spinale und bulbäre Muskelatrophie Kennedy AR Spinocerebelläre Ataxie SCA1, SCA2, SCA3, SCA6, SCA7, SCA17 Spondylocostal dysostosis [meduniwien.ac.at]

• Pallister-Hall Syndrome

  […] congenita · MODY 1 · Familial partial lipodystrophy 3 · SF1 XY gonadal dysgenesis 2.2: Barakat syndrome · Tricho–rhino–phalangeal syndrome 2.3: Greig cephalopolysyndactyly syndrome / Pallister-Hall syndrome · Denys–Drash syndrome · Duane-radial ray syndrome [enacademic.com]

  MID1 Orofaciodigitales-Syndrom OFD1 Osteogenesis Imperfecta COL1A1, COL1A2, SERPINF1, CRTAP, LEPRE1, FKBP10 Pachyonychia Congenita KRT6A Pallister-Hall syndrome GLI3 Parkinson disease, juvenile, type 2 PARK2 PDGFC_Research PDGFC Pelizäus Merzbacher PLP1 [meduniwien.ac.at]

• Abdominal Distension

  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]

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

  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]

• Broad Eyebrows

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

  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]

  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]

  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]

• 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]

• Broad Nasal Bridge

  Facial properties include prominent narrow chin, open mouth, cupped ears with protruding lobes, broad nasal bridge with rounded nasal tip, and wide set eyes. [mowatwilson.org]

  Facial features include square-shaped face with deep-set, widely spaced eyes, broad nasal bridge with a rounded nasal tip and a prominent pointed c read more [ctgt.net]

  Mowat-Wilson syndrome: a genetic ( inherited ) condition present at birth that features square-shaped face with deep-set, widely spaced eyes, a broad nasal bridge, pointed chin, uplifted earlobes, intellectual disability,the intestinal disorder Hirschsprung [medicinenet.com]

  They also have a broad nasal bridge with a rounded nasal tip; a prominent and pointed chin; large, flaring eyebrows; and uplifted earlobes with a dimple in the middle. [mowat-wilson.org]

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.

Treatment is supportive and symptomatic. [en.wikipedia.org]

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]

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]

Treatment Treatment Options: Treatment may be directed at specific defects but there is no treatment for the general disorder. Individuals can live to adulthood. Treatment is largely symptomatic. [disorders.eyes.arizona.edu]

There are two main types of clinical studies: Clinical trials determine if a new test or treatment for a disease is effective and safe by comparing groups receiving different tests/treatments. [rarediseases.info.nih.gov]

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

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 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]

Medical subspecialist care may be required if other organs are involved (e.g., a cardiologist and/or cardiac surgeon for congenital heart disease, gastroenterologist and or surgeon for Hirschsprung's disease or constipation.[8] Prognosis[edit] There is [en.wikipedia.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]

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]

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]

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

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]

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.