Adam MP, Conta J, Bean LJH. Classic Mowat-Wilson Syndrome. 2007 Mar 28 [updated 2026 Apr 23]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2026. PMID: 20301585.
Excerpt
Clinical characteristics: Classic Mowat-Wilson syndrome (MWS) is characterized by distinctive facial features (widely spaced eyes, broad eyebrows with a medial flare, low-hanging columella, prominent or pointed chin, open-mouth expression, and uplifted earlobes with a central depression), congenital heart defects with predilection for abnormalities of the pulmonary arteries and/or valves, Hirschsprung disease and/or chronic constipation, genitourinary anomalies (particularly hypospadias in males), and hypogenesis or agenesis of the corpus callosum. Most affected individuals have moderate-to-severe intellectual disability. Speech is typically limited to a few words or is absent, with relative preservation of receptive language skills. Growth restriction with microcephaly and epilepsy are also common. Most affected people have a happy demeanor and a wide-based gait that can sometimes be confused with Angelman syndrome.
Diagnosis/testing: The diagnosis of classic MWS is established in a proband with the typical recognizable dysmorphic facial features and developmental delay / intellectual disability and/or a heterozygous pathogenic variant in ZEB2 (most classic MWS-related ZEB2 pathogenic variants lead to predicted haploinsufficiency for the functional components of the ZEB2 protein) identified by molecular genetic testing.
Management: Treatment of manifestations: Care by the appropriate specialist for dental anomalies, seizures, ocular abnormalities, congenital heart defects, chronic constipation, Hirschsprung disease, genitourinary abnormalities, and pectus anomalies of the chest and/or foot/ankle anomalies; educational intervention and speech therapy beginning in infancy.
Surveillance: Annual eye examination in childhood to monitor for strabismus and refractive errors; monitoring for otitis media; regular developmental assessments to plan/refine educational interventions; periodic reevaluation by a clinical geneticist.
Genetic counseling: Classic MWS is an autosomal dominant disorder caused by a pathogenic variant in ZEB2, a heterozygous deletion of 2q22.3 involving ZEB2, or (rarely) a chromosome rearrangement that disrupts ZEB2. Almost all individuals reported to date have been simplex cases (i.e., a single occurrence in a family) resulting from a de novo genetic alteration; rarely, recurrence in a family has been reported when a parent has a low level of somatic or presumed gonadal mosaicism for a classic MWS-causing pathogenic variant. Individuals with classic MWS are not known to reproduce. Once the causative genetic alteration has been identified in the proband, prenatal testing may be offered to parents of a child with classic MWS because of the recurrence risk associated with the possibility of parental mosaicism or a balanced chromosome rearrangement.
Adam MP, Schelley S, Gallagher R, Brady AN, Barr K, Blumberg B, Shieh JT, Graham J, Slavotinek A, Martin M, Keppler-Noreuil K, Storm AL, Hudgins L. Clinical features and management issues in Mowat-Wilson syndrome. Am J Med Genet A. 2006 Dec 15;140(24):2730-41. doi: 10.1002/ajmg.a.31530. PMID: 17103451.
Abstract
Mowat-Wilson syndrome (MWS) is a relatively newly described multiple congenital anomaly/mental retardation syndrome. Haploinsufficiency of a gene termed ZFHX1B (also known as SIP1) on chromosome 2 is responsible for this condition, and clinical genetic testing for MWS recently became available. The majority of reports in the literature originate from Northern Europe and Australia. Here we report our clinical experience with 12 patients diagnosed with MWS within a 2-year period of time in the United States, with particular emphasis on clinical characteristics and management strategies. 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 the diagnosis. Medical issues in our cohort of patients included seizures (75%) with no predeliction for any particular seizure type; agenesis of the corpus callosum (60% of our patients studied); congenital heart defects (75%), particularly involving the pulmonary arteries and/or valves; hypospadias (55% of males); severely impaired or absent speech (100% of individuals over 1 year of age) with relatively spared receptive language; and Hirschsprung disease (50%) or chronic constipation (25%). The incidence of MWS is unknown, but based on the number of patients identified in a short period of time within the US, it is likely greatly under recognized. MWS should be considered in any individual with severely impaired or absent speech, especially in the presence of seizures and anomalies involving the pulmonary arteries (particularly pulmonary artery sling) or pulmonary valves.
Ju Y, Ji TY. Electro-clinical features of Mowat-Wilson syndrome: A retrospective study of 31 children in mainland China. Epileptic Disord. 2026 Apr;28(2):344-358. doi: 10.1002/epd2.70149. Epub 2025 Dec 27. PMID: 41454799; PMCID: PMC13084205.
Abstract
Objective: To summarize the electro-clinical and genetic characteristics of children with Mowat-Wilson syndrome (MWS).
Methods: This study is a hospital-based case series analyzing clinical data from 31 pediatric patients with MWS and epilepsy treated at Peking University First Hospital between June 2020 and December 2024. Information on seizures, electroencephalographic features, genetic characteristics, treatment, and prognosis was summarized and analyzed using descriptive statistics.
Results: Among the 31 children (16 males and 15 females), seizure onset occurred at a median age of 25.5 months (range: 1-113 months). Eighteen cases (58.1%, 18/31) began with fever-induced seizures; all 31 children experienced focal seizures, and 16 (51.6%, 16/31) exhibited atypical seizure presentations. Twelve (38.7%, 12/31) experienced seizures accompanied by gastrointestinal (GI) symptoms. Two children had myoclonic seizures, one had epileptic spasms, and another had atypical absence seizures. Ten (32.3%, 10/31) experienced convulsive status epilepticus. Electroencephalographic findings evolved from posterior head-dominant discharges to multifocal or anterior head-dominant discharges, with a significant increase in discharges during sleep. All 31 children had de novo ZEB2 variants, including 27 with single-nucleotide variants (SNVs) or insertions/deletions (indels) and four with copy number variants. Among the SNVs/indels, nonsense (13) and frameshift (12) variants predominated. One patient with rare seizures did not receive anti-seizure medication (ASM). Thirty received ASMs; both levetiracetam and valproic acid, used as monotherapy or in combination, proved effective. Sixteen children achieved seizure control for more than 6 months, and seven maintained seizure control for over 1 year.
Significance: Our findings reveal the electro-clinical characteristics, genetic variants, and effective treatments associated with MWS, providing an important basis for clinical diagnosis and management.
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