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

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 (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Book Volume: 20

Pages Range: 965-975

Journal Issue: 9

DOI: 10.1038/gim.2017.221

Abstract

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.

Authors with CRIS profile

Involved external institutions

University of Bologna / Università di Bologna Italy (IT) Azienda Unità Sanitaria Locale die Reggio Emilia Italy (IT) Great Ormond Street Hospital (GOSH) United Kingdom (GB) Tepecik Education and Research Hospital Turkey (TR) University of Turin / Università degli Studi di Torino (UNITO) Italy (IT) Università degli Studi di Ferrara Italy (IT) University of Washington United States (USA) (US) Ente ospedaliero Ospedali Galliera Italy (IT) Centre Hospitalier Universitaire de Bordeaux / CHU Bordeaux France (FR) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven Belgium (BE) Università degli studi "La Sapienza" Italy (IT) Alexandria University / جامعة الإسكندرية‎‎ Egypt (EG) Università degli Studi di Catania Italy (IT) University of Southern Denmark / Syddansk Universitet Denmark (DK) Catholic University of the Sacred Heart / Università Cattolica del Sacro Cuore Italy (IT) Istituto di ricovero e cura a carattere scientifico (IRCCS) Italy (IT) Centre Hospitalier Régional Universitaire de Tours France (FR) Policlinico San Matteo Pavia Fondazione IRCCS Italy (IT) Copenhagen University Hospital Denmark (DK) ASST Rhodense Italy (IT) Erasmus University Rotterdam (EUR) / Erasmus Universiteit Rotterdam Netherlands (NL) Azienda Ospedaliera Gaetano Rummo Via dell’Angelo Italy (IT) Institute for Mother and Child Health Care Serbia (RS) Azienda Provinciale per i Servizi Sanitari Italy (IT) Wrocław Medical University / Uniwersytet Medyczny we Wrocławiu Poland (PL) Arcispedale Santa Maria Nuova Italy (IT) Institute of Mother and Child / Instytut Matki I Dziecka Poland (PL) Sveučilište u Rijeci / University of Rijeka Croatia (HR) Kennedy Centret Denmark (DK) Hospital San Pedro Spain (ES) Universitätsklinikum Magdeburg A.ö.R. Germany (DE) University of Zurich / Universität Zürich (UZH) Switzerland (CH) Foundation of the Carlo Besta Neurological Institute (IRCCS) Italy (IT) Università degli Studi di Modena e Reggio Emilia (UNIMORE) Italy (IT) University of Milano-Bicocca / Università degli Studi di Milano-Bicocca, UNIMIB Italy (IT) Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia Italy (IT) Università degli Studi di Siena (UNISI) / University of Siena Italy (IT) Zealand University Hospital Denmark (DK) University of São Paulo / Universidade de São Paulo (USP) Brazil (BR) Università degli studi di Milano Italy (IT) Leiden University Netherlands (NL) Copenhagen University Hospital Hvidovre Denmark (DK) Dartmouth-Hitchcock Medical Center (DHMC) United States (USA) (US) Eastern Virginia Medical School United States (USA) (US) University of Belgrade / Универзитет у Београду Serbia (RS) Poznan University of Medical Sciences / Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu Poland (PL) Azienda Ospedaliera di Rilievo Nazionale Santobono Pausilipon Italy (IT) L'Azienda Ospedaliera di Rilievo Nazionale Antonio Cardarelli Italy (IT) Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico Italy (IT) University Hospital Ghent Belgium (BE)

How to cite

APA:

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. https://doi.org/10.1038/gim.2017.221

MLA:

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.

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