Clinical features and management issues in Mowat–Wilson syndrome

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.

Phenotype and genotype of 87 patients with Mowat–Wilson syndrome and recommendations for care

“…3,4 In 2002 Zweier et al 5 further delineated the phenotype of MWS with or without HSCR, invariably characterized by ZEB2 gene defects, and proposed that the condition be named Mowat-Wilson syndrome. More than 300 patients have been reported so far [6][7][8][9][10][11][12][13][14][15][16][17] (additional reviewed articles are listed in Supplementary File S1 online).…”

“…The purpose of the article is to assist clinicians to identify the disease and to provide them with updated care recommendations for patient management. 13 …”

Avoiding Pitfalls in Molecular Genetic Testing

“…10,11 According to prior publications, there may be variability in the presence and/or age of onset for some features (eg, microcephaly, short stature/growth parameters). 10,12 Both of our patients showed Hirschsprung disease, microcephaly, eye abnormalities, delayed growth, significant developmental delay/mental retardation, and seizures. The first patient additionally showed a cardiac anomaly, genitourinary developmental anomaly, and partial absence of the corpus callosum, which were not reported in the second patient.…”

“…The first patient additionally showed a cardiac anomaly, genitourinary developmental anomaly, and partial absence of the corpus callosum, which were not reported in the second patient. At present, in Mowat-Wilson syndrome, the clinical phenotype does not appear to significantly change according to the underlying genotype 10,12 ; almost all patients, regardless of the specific underlying ZEB2 abnormality (ie, small mutations or large deletions), have the facial gestalt and moderate to severe mental retardation, supporting the concept that this syndrome results from ZEB2 haploinsufficiency rather than it being a contiguous gene syndrome. 10 Approximately 80% of the mutations described in ZEB2 are nonsense mutations and frameshift mutations (small insertions or deletions) 11,13,14 that are detectable by Sanger sequencing.…”

Psychopharmacological Management of Problem Behaviors in Mowat–Wilson Syndrome

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M owat-Wilson Syndrome (MWS) is a neurodevelopmental disorder characterized by intellectual disability (ID), Hirschsprung disease, agenesis of the corpus collosum, seizures, expressive language deficits, a distinct facial gestalt, congenital heart defects, and behavioral dysregulation, with a happy and social demeanor (Adam et al 2006). It is caused by de novo heterozygous mutations in the ZEB2 gene, which is produced at high levels in postmitotic neocortical neurons and may play a role in determining neuronal cell fate in corticogenesis (Seuntjens et al 2009).

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