title: Clinical spectrum of eye malformations in four patients with Mowat-Wilson syndrome.
abstract: Mowat-Wilson syndrome (MWS) is a rare genetic syndrome characterized by a specific facial gestalt, intellectual deficiency, Hirschsprung disease and multiple congenital anomalies. Heterozygous mutations or deletions in the zinc finger E-box-binding homeobox2 gene (ZEB2) cause MWS. ZEB2 encodes for Smad-interacting protein 1, a transcriptional co-repressor involved in TGF-beta and BMP pathways and is strongly expressed in early stages of development in mice. Eye abnormalities have rarely been described in patients with this syndrome. Herein, we describe four patients (two males and two females; mean age 7 years) with MWS and eye malformations. Ocular anomalies included, iris/retinal colobomas, atrophy or absence of the optic nerve, hyphema, and deep refraction troubles, sometimes with severe visual consequences. All eye malformations were asymmetric and often unilateral and all eye segments were affected, similarly to the nine MWS cases with ophthalmological malformations previously reported (iris/chorioretinal/optic disc coloboma, optic nerve atrophy, retinal epithelium atrophy, cataract, and korectopia). In human embryo, ZEB2 is expressed in lens and neural retina. Using the present report and data from the literature, we set out to determine whether or not the presence of eye manifestations could be due to specific type or location of mutations. We concluded that the presence of eye malformations, although a rare feature in MWS, should be considered as a part of the clinical spectrum of the condition.
authors.affiliation: Département de Pédiatrie 1, Hôpital d'Enfants, CHU Dijon et Université de Bourgogne, Dijon, France.
authors.forename: A
authors.initials: A
authors.lastname: Bourchany
authors.affiliation: Service de Biochimie Génétique, AP-HP, Université Paris-Est, Hôpital Henri Mondor, Créteil, France.
authors.forename: I
authors.initials: I
authors.lastname: Giurgea
authors.affiliation: Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, FHU TRANSLAD, Hôpital d'Enfants, CHU Dijon et Université de Bourgogne, Dijon, France.
authors.forename: J
authors.initials: J
authors.lastname: Thevenon
authors.affiliation: Unité de Génétique Clinique, Hôpital Charles Nicolle, Université de Rouen, France.
authors.forename: A
authors.initials: A
authors.lastname: Goldenberg
authors.affiliation: Centre d'activité de génétique clinique et oncogénétique, Hôpital Sud, Université de Picardie Jules Verne, Amiens, France.
authors.forename: G
authors.initials: G
authors.lastname: Morin
authors.affiliation: Service d'Ophtalmologie, centre Saint-Victor, CHU d'Amiens, Université de Picardie Jules-Verne, Amiens, France.
authors.forename: D
authors.initials: D
authors.lastname: Bremond-Gignac
authors.affiliation: Service d'Ophtalmologie, CHU Dijon et Université de Bourgogne, Dijon, France.
authors.forename: C
authors.initials: C
authors.lastname: Paillot
authors.affiliation: Service d'Ophtalmologie, CHU Dijon et Université de Bourgogne, Dijon, France.
authors.forename: P O
authors.initials: PO
authors.lastname: Lafontaine
authors.affiliation: Clinique Saint Nicolas, Toulouse, France.
authors.forename: D
authors.initials: D
authors.lastname: Thouvenin
authors.affiliation: Service d'Ophtalmologie, Hôpital Charles Nicolle, Université de Rouen, France.
authors.forename: J
authors.initials: J
authors.lastname: Massy
authors.affiliation: Service d'Ophtalmologie, Hôpital Charles Nicolle, Université de Rouen, France.
authors.forename: A
authors.initials: A
authors.lastname: Duncombe
authors.affiliation: Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, FHU TRANSLAD, Hôpital d'Enfants, CHU Dijon et Université de Bourgogne, Dijon, France.
authors.forename: C
authors.initials: C
authors.lastname: Thauvin-Robinet
authors.affiliation: Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, FHU TRANSLAD, Hôpital d'Enfants, CHU Dijon et Université de Bourgogne, Dijon, France.
authors.forename: A
authors.initials: A
authors.lastname: Masurel-Paulet
authors.affiliation: Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, FHU TRANSLAD, Hôpital d'Enfants, CHU Dijon et Université de Bourgogne, Dijon, France.
authors.forename: S El
authors.initials: SE
authors.lastname: Chehadeh
authors.affiliation: Département de Pédiatrie 1, Hôpital d'Enfants, CHU Dijon et Université de Bourgogne, Dijon, France.
authors.forename: F
authors.initials: F
authors.lastname: Huet
authors.affiliation: Service d'Ophtalmologie, CHU Dijon et Université de Bourgogne, Dijon, France.
authors.forename: A
authors.initials: A
authors.lastname: Bron
authors.affiliation: Service d'Ophtalmologie, CHU Dijon et Université de Bourgogne, Dijon, France.
authors.forename: C
authors.initials: C
authors.lastname: Creuzot-Garcher
authors.affiliation: Service de Génétique Médicale, Hôpital Necker-Enfants Malades, Université René-Descartes Paris 5, France.
authors.forename: S
authors.initials: S
authors.lastname: Lyonnet
authors.affiliation: Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, FHU TRANSLAD, Hôpital d'Enfants, CHU Dijon et Université de Bourgogne, Dijon, France.
authors.forename: L
authors.initials: L
authors.lastname: Faivre
mesh_terms: D000293:Adolescent; D001284:Atrophy / Q000473:pathology; D002386:Cataract / Q000473:pathology; D002675:Child, Preschool; D003103:Coloboma / Q000473:pathology; D005123:Eye / Q000473:pathology*; D019066:Facies; D005260:Female; D006627:Hirschsprung Disease / Q000235:genetics* / Q000473:pathology*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008831:Microcephaly / Q000235:genetics* / Q000473:pathology*; D009154:Mutation / Q000235:genetics; D009900:Optic Nerve / Q000473:pathology; D012097:Repressor Proteins / Q000235:genetics*; D055213:Retinal Pigment Epithelium / Q000473:pathology; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D018398:Homeodomain Proteins; D012097:Repressor Proteins; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2
keywords: Mowat-Wilson; ZEB2; eye malformation; syndromic Hirschsprung disease