At E14.5, Ankrd11 expression in the craniofacial complex is closely associated with developing bony structures, while expression at birth is markedly decreased. They show increased severity of several clinical manifestations described for KBG syndrome, such as cleft palate, retrognathia, midfacial hypoplasia, and reduced calvarial growth. Mice with a homozygous Ankrd11 deletion in neural crest cells (Ankrd11 ncko) die at birth. Here, we report that mice with heterozygous deletion of Ankrd11 in neural crest cells (Ankrd11 nchet) display a mild midfacial hypoplasia including reduced midfacial width and a persistent open fontanelle, both of which mirror KBG syndrome patient facial phenotypes. Quantitative analysis of 3D images of KBG syndromic subjects shows an overall reduction in the size of the middle and lower face. Despite this, the dramatic phenotype and precise role of ANKRD11 in embryonic craniofacial development remain unexplored. Craniofacial abnormalities include a distinct facial gestalt, delayed bone age, tooth abnormalities, delayed fontanelle closure, and frequently cleft or submucosal palate. ANKRD11 gene variants, or microdeletions of the 16q24.3 chromosomal region encompassing the ANKRD11 gene, cause KBG syndrome, a rare autosomal dominant congenital disorder with variable neurodevelopmental and craniofacial involvement. Ankyrin Repeat Domain 11 ( ANKRD11) is a chromatin regulator that has previously been shown to control neural stem cell fates via modulation of histone acetylation. 6Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, CanadaĮpigenetic and chromatin regulation of craniofacial development remains poorly understood.5Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.4Cell Biology Program, Hospital for Sick Children, Toronto, ON, Canada.3Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada. 2Department of Cell Biology & Anatomy, Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, Canada.1School of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.Egan 4,5†, Benedikt Hallgrímsson 2†, Daniel Graf 1,3*† and Anastassia Voronova 3,6*† Daniela Marta Roth 1†, Pranidhi Baddam 1†, Haiming Lin 1†, Marta Vidal-García 2†, Jose David Aponte 2†, Sarah-Thea De Souza 1†, Devyn Godziuk 3, Adrianne Eve Scovil Watson 3, Tim Footz 3, Nathan F.
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