CHARGE-like presentation, craniosynostosis and mild Mowat-Wilson syndrome diagnosed by recognition of the distinctive facial gestalt in a cohort of 28 new cases

Mowat-Wilson syndrome(MWS) is characterized bymoderate 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, andmicrocephaly. Less commonclinical features include ocular anomalies, craniosynostosis, mild intellectual disability, and choanal atresia. These casesmay bemore difficult to diagnose. In this report, we add 28MWS patients withmolecular confirmation of ZEB2 mutation, including seven with an uncommon presenting feature. Among the "unusual" patients, two patients hadclinical featuresof charge syndrome includingchoanalatresia, coloboma, cardiac defects, genitourinary anomaly (1/2), and severe intellectual disability; two patients had craniosynostosis; and three patientshadmildintellectualdisability. Sixteenpatients 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 withMWSwith unusual features, and is the first report of MWS in children previously thought to have CHARGE syndrome. Thesepatients highlight the importance of facialgestalt in the accurate identification ofMWSwhen less common features are present.