title: CHARGE-like presentation, craniosynostosis and mild Mowat-Wilson Syndrome diagnosed by recognition of the distinctive facial gestalt in a cohort of 28 new cases.
abstract: Mowat-Wilson syndrome (MWS) is characterized by moderate to severe intellectual disability and distinctive facial features in association with variable structural congenital anomalies/clinical features including congenital heart disease, Hirschsprung disease, hypospadias, agenesis of the corpus callosum, short stature, epilepsy, and microcephaly. Less common clinical features include ocular anomalies, craniosynostosis, mild intellectual disability, and choanal atresia. These cases may be more difficult to diagnose. In this report, we add 28 MWS patients with molecular confirmation of ZEB2 mutation, including seven with an uncommon presenting feature. Among the "unusual" patients, two patients had clinical features of charge syndrome including choanal atresia, coloboma, cardiac defects, genitourinary anomaly (1/2), and severe intellectual disability; two patients had craniosynostosis; and three patients had mild intellectual disability. Sixteen patients have previously-unreported mutations in ZEB2. Genotype-phenotype correlations were suggested in those with mild intellectual disability (two had a novel missense mutation in ZEB2, one with novel splice site mutation). This report increases the number of reported patients with MWS with unusual features, and is the first report of MWS in children previously thought to have CHARGE syndrome. These patients highlight the importance of facial gestalt in the accurate identification of MWS when less common features are present.
authors.affiliation: Division of Craniofacial Medicine, Seattle Children's Hospital, Seattle, WA.
authors.forename: Tara L
authors.initials: TL
authors.lastname: Wenger
authors.forename: Margaret
authors.initials: M
authors.lastname: Harr
authors.forename: Stefania
authors.initials: S
authors.lastname: Ricciardi
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bhoj
authors.forename: Avni
authors.initials: A
authors.lastname: Santani
authors.forename: Margaret P
authors.initials: MP
authors.lastname: Adam
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Barnett
authors.forename: Rebecca
authors.initials: R
authors.lastname: Ganetzky
authors.forename: Donna M
authors.initials: DM
authors.lastname: McDonald-McGinn
authors.forename: Domenica
authors.initials: D
authors.lastname: Battaglia
authors.forename: Stefania
authors.initials: S
authors.lastname: Bigoni
authors.forename: Angelo
authors.initials: A
authors.lastname: Selicorni
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sorge
authors.forename: Matteo Della
authors.initials: MD
authors.lastname: Monica
authors.forename: Francesca
authors.initials: F
authors.lastname: Mari
authors.forename: Elena
authors.initials: E
authors.lastname: Andreucci
authors.forename: Silvia
authors.initials: S
authors.lastname: Romano
authors.forename: Guido
authors.initials: G
authors.lastname: Cocchi
authors.forename: Salvatore
authors.initials: S
authors.lastname: Savasta
authors.forename: Baris
authors.initials: B
authors.lastname: Malbora
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Marangi
authors.forename: Livia
authors.initials: L
authors.lastname: Garavelli
authors.forename: Marcella
authors.initials: M
authors.lastname: Zollino
authors.forename: Elaine H
authors.initials: EH
authors.lastname: Zackai
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000328:Adult; D058747:CHARGE Syndrome / Q000175:diagnosis* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003398:Craniosynostoses / Q000175:diagnosis* / Q000235:genetics; D005145:Face / Q000002:abnormalities*; D019066:Facies; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D006627:Hirschsprung Disease / Q000175:diagnosis* / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008831:Microcephaly / Q000175:diagnosis* / Q000235:genetics; D009154:Mutation / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D055815:Young Adult; 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: CHARGE syndrome; Mowat-Wilson syndrome; craniosynostosis; intellectual disability; minor malformations