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.
Highlights
Mowat-Wilson Syndrome (MWS) (OMIM # 235730) is a condition due to ZEB2 gene defects [1] and is characterized by a wide clinical spectrum that ranges from mild to severe forms [2].It is a rare syndrome: in the literature a little less than 300 patients have been described so far [3,4,5,6,7,8,9,10,11,12,13,14,15]
Other clinical aspects associated with MWS are constipation (43.5%), Hirschsprung disease (30.6%), urogenital anomalies (61.25%; in particular hypospadias and cryptorchidism), and short stature [7]
Consistent with the role of the transcription factor ZEB2 in regulating intracortical and cortical-subcortical connections [33], the corpus callosum abnormalities turn out to be a hallmark of brain MRI findings in these individuals, presenting in about 75% of patients
Summary
Mowat-Wilson Syndrome (MWS) (OMIM # 235730) is a condition due to ZEB2 gene defects (heterozygous mutation or deletion) [1] and is characterized by a wide clinical spectrum that ranges from mild (usually associated with missense mutations) to severe forms [2]. It is a rare syndrome: in the literature a little less than 300 patients have been described so far [3,4,5,6,7,8,9,10,11,12,13,14,15]. We will analyze the neurological and neurodevelopmental phenotype in MWS focusing on ZEB2 function in brain development
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