Phenotype and genotype of 87 patients with Mowat-Wilson syndrome and recommendations for care

Journal article

Publication Details

Author(s): Ivanovski I, Djuric O, Caraffi SG, Santodirocco D, Pollazzon M, Rosato S, Cordelli DM, Abdalla E, Accorsi P, Adam MP, Ajmone PF, Badura-Stronka M, Baldo C, Baldi M, Bayat A, Bigoni S, Bonvicini F, Breckpot J, Callewaert B, Cocchi G, Cuturilo G, De Brasi D, Devriendt K, Dinulos MB, Hjortshoj TD, Epifanio R, Faravelli F, Fiumara A, Formisano D, Giordano L, Grasso M, Gronborg S, Iodice A, Iughetti L, Kuburovic V, Kutkowska-Kazmierczak A, Lacombe D, Lo Rizzo C, Luchetti A, Malbora B, Mammi I, Mari F, Montorsi G, Moutton S, Moller RS, Muschke P, Nielsen JEK, Obersztyn E, Pantaleoni C, Pellicciari A, Pisanti MA, Prpic I, Poch-Olive ML, Raviglione F, Renieri A, Ricci E, Rivieri F, Santen GW, Savasta S, Scarano G, Schanze I, Selicorni A, Silengo M, Smigiel R, Spaccini L, Sorge G, Szczaluba K, Tarani L, Tone LG, Toutain A, Trimouille A, Valera ET, Vergano SS, Zanotta N, Zenker M, Conidi A, Zollino M, Rauch A, Zweier C, Garavelli L
Journal: Genetics in Medicine
Publication year: 2018
Volume: 20
Journal issue: 9
Pages range: 965-975
ISSN: 1098-3600


PURPOSE: Mowat-Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype-phenotype correlations of MWS.
METHODS: In a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations.
RESULTS: All anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluation of MWS to date, we define its clinical evolution occurring with age and derive suggestions for patient management. Furthermore, we observe that its severity correlates with the kind of ZEB2 variation involved, ranging from ZEB2 locus deletions, associated with severe phenotypes, to rare nonmissense intragenic mutations predicted to preserve some ZEB2 protein functionality, accompanying milder clinical presentations.
CONCLUSION: Knowledge of the phenotypic spectrum of MWS and its correlation with the genotype will improve its detection rate and the prediction of its features, thus improving patient care.

External institutions with authors

Alexandria University / جامعة الإسكندرية‎‎
Arcispedale Santa Maria Nuova
ASST Rhodense
Azienda Ospedaliera di Rilievo Nazionale Santobono Pausilipon
Azienda Ospedaliera Gaetano Rummo Via dell’Angelo
Azienda Provinciale per i Servizi Sanitari
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Azienda Unità Sanitaria Locale die Reggio Emilia
Catholic University of the Sacred Heart / Università Cattolica del Sacro Cuore
Centre Hospitalier Régional Universitaire de TOURS
Centre Hospitalier Universitaire de Bordeaux / CHU Bordeaux
Copenhagen University Hospital
Copenhagen University Hospital Hvidovre
Eastern Virginia Medical School
Ente ospedaliero Ospedali Galliera
Erasmus University Rotterdam (EUR) / Erasmus Universiteit Rotterdam
Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
Foundation of the Carlo Besta Neurological Institute (IRCCS)
Great Ormond Street Hospital for Children NHS Foundation Trust
Hospital San Pedro
Institute for Mother and Child Health Care
Institute of Mother and Child
Istituto di ricovero e cura a carattere scientifico (IRCCS)
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
Kennedy Centret
L'Azienda Ospedaliera di Rilievo Nazionale Antonio Cardarelli
Leiden University
Policlinico San Matteo Pavia Fondazione IRCCS
Poznan University of Medical Sciences / Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu
Sveučilište u Rijeci / University of Rijeka
Tepecik Education and Research Hospital
Università degli Studi di Catania
Università degli Studi di Ferrara
Università degli studi di Milano
Università degli Studi di Modena e Reggio Emilia (UNIMORE)
Università degli Studi di Siena (UNISI) / University of Siena
Università degli studi "La Sapienza"
Universitätsklinikum Magdeburg A.ö.R.
Universität Zürich (UZH)
University Hospital Ghent
University of Belgrade / Универзитет у Београду
University of Bologna / Università di Bologna
University of Milano-Bicocca / Università degli Studi di Milano-Bicocca, UNIMIB
University of São Paulo / Universidade de São Paulo (USP)
University of Southern Denmark / Syddansk Universitet
University of Turin / Università degli Studi di Torino (UNITO)
University of Washington
Wrocław Medical University / Uniwersytet Medyczny we Wrocławiu
Zealand University Hospital

How to cite

Ivanovski, I., Djuric, O., Caraffi, S.G., Santodirocco, D., Pollazzon, M., Rosato, S.,... Garavelli, L. (2018). Phenotype and genotype of 87 patients with Mowat-Wilson syndrome and recommendations for care. Genetics in Medicine, 20(9), 965-975.

Ivanovski, Ivan, et al. "Phenotype and genotype of 87 patients with Mowat-Wilson syndrome and recommendations for care." Genetics in Medicine 20.9 (2018): 965-975.


Last updated on 2018-30-11 at 08:23