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Review
. 2021 Jun 27;12(7):982.
doi: 10.3390/genes12070982.

Neurological Phenotype of Mowat-Wilson Syndrome

Duccio Maria Cordelli  1 , Veronica Di Pisa  1 , Anna Fetta  1 , Livia Garavelli  2 , Lucia Maltoni  1 , Luca Soliani  1 , Emilia Ricci  3
Affiliations
Review

Neurological Phenotype of Mowat-Wilson Syndrome

Duccio Maria Cordelli et al. Genes (Basel). .

Abstract

Mowat-Wilson Syndrome (MWS) (OMIM # 235730) is a rare disorder due to ZEB2 gene defects (heterozygous mutation or deletion). The ZEB2 gene is a widely expressed regulatory gene, extremely important for the proper prenatal development. MWS is characterized by a specific facial gestalt and multiple musculoskeletal, cardiac, gastrointestinal, and urogenital anomalies. The nervous system involvement is extensive and constitutes one of the main features in MWS, heavily affecting prognosis and life quality of affected individuals. This review aims to comprehensively organize and discuss the neurological and neurodevelopmental phenotype of MWS. First, we will describe the role of ZEB2 in the formation and development of the nervous system by reviewing the preclinical studies in this regard. ZEB2 regulates the neural crest cell differentiation and migration, as well as in the modulation of GABAergic transmission. This leads to different degrees of structural and functional impairment that have been explored and deepened by various authors over the years. Subsequently, the different neurological aspects of MWS (head and brain malformations, epilepsy, sleep disorders, and enteric and peripheral nervous system involvement, as well as developmental, cognitive, and behavioral features) will be faced one at a time and extensively examined from both a clinical and etiopathogenetic point of view, linking them to the ZEB2 related pathways.

Keywords: GABAergic transmission; ZEB2; corpus callosum; epilepsy; intellectual disability.; neural crest; neurodevelopmental delay; sleep disorders.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Role of ZEB2 haploinsufficiency in central and peripheral nervous system development.
Figure 2
Figure 2
EEG evolution at 0 (A), 3 (C,D), 5 (E,F) and 9 (G,H) years old, and RM features (B) of a MWS individual. Caption: At birth, electroencephalographic activity is essentially normal (A). With time, a worsening is observed, with an increase in paroxysmal abnormalities in wakefulness (C,E,G), dramatically activated during sleep (D,F,H). MRI images performed at 4 months show complete agenesis of the corpus callosum (B). Interestingly, abnormalities in sleep can sometimes appear asynchronous although bilateral: this is probably related to this type of malformation. Note: low frequency filter: 1.6 Hz; high frequency filter: 60 Hz; paper speed: 20mm/sec; sensitivity: 150 microV/cm (A,C,D,E,F), 200 microV/cm (G) and 100 microV/cm (H).
See this image and copyright information in PMC

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