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

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

• Enuresis

  The Parental Questionnaire: Enuresis/Urinary Incontinence, as well as the Developmental Behaviour Checklist (DBC) were completed by parents or care-givers. [ncbi.nlm.nih.gov]

• 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]

  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. [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]

• Muscle Hypotonia

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

• 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]

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

  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]

• Chordee

  Clinical findings can also include cryptorchidism (37% of males), bifid scrotum, vesicoureteral reflux (VUR), hydronephrosis, short penile chordee or "webbed penis," septum of the vagina, duplex kidney, pelvic kidney, hydrocele, and multicystic renal [ncbi.nlm.nih.gov]

• Nocturnal Enuresis

  OUTCOMES AND RESULTS: 97.7% of persons with MWS had incontinence (nocturnal enuresis 74.4%; daytime urinary incontinence 76.2%; fecal incontinence 81.4%). [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.

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.