Mowat-Wilson Syndrome: Growth Charts
Authors: Ivanovski Ivan , Djuric Olivera , Broccoli Serena , Caraffi Stefano Giuseppe , Patrizia Accorsi , Adam Margaret P , Avela Kristina , Badura-Stronka Magdalena , Bayat Allan , Clayton-Smith Jill , Cocco Isabella , Cordelli Duccio Maria , Cuturilo Goran , Pisa Veronica Di , Garcia Juliette Dupont , Gastaldi Roberto , Giordano Lucio , Guala Andrea , Hoei-Hansen Christina , Inaba Mie , Iodice Alessandro , Nielsen Jens Erik Klint , Kuburovic Vladimir , Lazalde-Medina Brissia , Malbora Baris , Mizuno Seiji , Moldovan Oana , Møller Rikke S , Muschke Petra , Otelli Valeria , Pantaleoni Chiara , Piscopo Carmelo , Poch-Olive Maria Luisa , Prpic Igor , Purificacion Marin Reina , Raviglione Federico , Ricci Emilia , Scarano Emanuela , Simonte Graziella , Smigiel Robert , Tanteles George , Tarani Luigi , Trimouille Aurelien , Valera Elvis Terci , Vergano Samantha Schrier , Writzl Karin , Callewaert Bert , Savasta Salvatore , Street Maria Elisabeth , Iughetti Lorenzo , Bernasconi Sergio , Rossi Paolo Giorgi , Garavelli Livia 
Published: March 2020

Abstract
Background: Mowat–Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of the ZEB2 gene, and characterized by typical face, moderate-to-severe intellectual disability, epilepsy, Hirschsprung disease, and multiple congenital anomalies, including genital anomalies, congenital heart defects, agenesis of the corpus callosum, and eye defects. To date, a clear description of the physical development of MWS patients does not exist. The aim of the study is to provide up-to-date growth charts specific for infants and children with MWS. The charts for males and females aged from 0 to 16 years were constructed using a total of 2,865 measurements of 99 MWS patients, of different ancestries. The data were collected through extensive collaboration with the Italian MWS association (AIMW) and the MWS Foundation. To model the growth charts, the GAMLSS package for the R statistical program was used. Height, weight, body mass index (BMI) and head circumference were compared to healthy children using CDC growth charts.Results: In newborns, weight and length were distributed as in the general population, while head circumference was slighlty smaller, with the average below the 30th centile. Weight and height distribution was slightly shifted to lower values than the general population until the age of 7, when the difference increased, with 50% of affected children below the 5th centile of the general population. BMI distribution was similar to that of non-affected children until the age of 7, at which point values in MWS children increase with a less steep slope, particuarly in males. Microcephaly is sometimes present at birth, but more often develops gradually in infancy and not all children were microcephalic (at least 2 SD below the mean) and the head circumference was often between the 3rd and the 10th centile. Most patients are of slender build.Conclusions: These charts contribute to the understanding of the natural history of MWS and should assist pediatricians and other caregivers in providing optimal care to MWS individuals with problems related to physical growth. This is the first study on growth in patients with MWS.