TY - JOUR

T1 - Phenotype and genotype of 87 patients with Mowat-Wilson syndrome and recommendations for care

AU - Ivanovski, Ivan

AU - Djuric, Olivera

AU - Caraffi, Stefano Giuseppe

AU - Santodirocco, Daniela

AU - Pollazzon, Marzia

AU - Rosato, Simonetta

AU - Cordelli, Duccio Maria

AU - Abdalla, Ebtesam

AU - Accorsi, Patrizia

AU - Adam, Margaret P

AU - Ajmone, Paola Francesca

AU - Badura-Stronka, Magdalena

AU - Baldo, Chiara

AU - Baldi, Maddalena

AU - Bayat, Allan

AU - Bigoni, Stefania

AU - Bonvicini, Federico

AU - Breckpot, Jeroen

AU - Callewaert, Bert

AU - Cocchi, Guido

AU - Cuturilo, Goran

AU - De Brasi, Daniele

AU - Devriendt, Koenraad

AU - Dinulos, Mary Beth

AU - Hjortshøj, Tina Duelund

AU - Epifanio, Roberta

AU - Faravelli, Francesca

AU - Fiumara, Agata

AU - Formisano, Debora

AU - Giordano, Lucio

AU - Grasso, Marina

AU - Grønborg, Sabine

AU - Iodice, Alessandro

AU - Iughetti, Lorenzo

AU - Kuburovic, Vladimir

AU - Kutkowska-Kazmierczak, Anna

AU - Lacombe, Didier

AU - Lo Rizzo, Caterina

AU - Luchetti, Anna

AU - Malbora, Baris

AU - Mammi, Isabella

AU - Mari, Francesca

AU - Montorsi, Giulia

AU - Moutton, Sebastien

AU - Møller, Rikke S

AU - Muschke, Petra

AU - Nielsen, Jens Erik Klint

AU - Obersztyn, Ewa

AU - Pantaleoni, Chiara

AU - Pellicciari, Alessandro

AU - Pisanti, Maria Antonietta

AU - Prpic, Igor

AU - Poch-Olive, Maria Luisa

AU - Raviglione, Federico

AU - Renieri, Alessandra

AU - Ricci, Emilia

AU - Rivieri, Francesca

AU - Santen, Gijs W

AU - Savasta, Salvatore

AU - Scarano, Gioacchino

AU - Schanze, Ina

AU - Selicorni, Angelo

AU - Silengo, Margherita

AU - Smigiel, Robert

AU - Spaccini, Luigina

AU - Sorge, Giovanni

AU - Szczaluba, Krzysztof

AU - Tarani, Luigi

AU - Tone, Luis Gonzaga

AU - Toutain, Annick

AU - Trimouille, Aurelien

AU - Valera, Elvis Terci

AU - Vergano, Samantha Schrier

AU - Zanotta, Nicoletta

AU - Zenker, Martin

AU - Conidi, Andrea

AU - Zollino, Marcella

AU - Rauch, Anita

AU - Zweier, Christiane

AU - Garavelli, Livia

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Abnormalities, Multiple/genetics

KW - Adolescent

KW - Adult

KW - Child

KW - Child, Preschool

KW - Facies

KW - Female

KW - Genetic Association Studies/methods

KW - Genotype

KW - Hirschsprung Disease/diagnosis

KW - Humans

KW - Infant

KW - Intellectual Disability/diagnosis

KW - Male

KW - Microcephaly/diagnosis

KW - Mutation

KW - Phenotype

KW - Zinc Finger E-box Binding Homeobox 2/genetics

U2 - 10.1038/gim.2017.221

DO - 10.1038/gim.2017.221

M3 - Journal article

C2 - 29300384

VL - 20

SP - 965

EP - 975

JO - Genetics in Medicine

JF - Genetics in Medicine

SN - 1098-3600

IS - 9

ER -