genes G C A T T A C G G C A T Review Growth Restriction and Genomic Imprinting-Overlapping Phenotypes Support the Concept of an Imprinting Network Thomas Eggermann 1, * , Justin H. Davies 2 , Maithé Tauber 3 , Erica van den Akker 4 , Anita Hokken-Koelega 5 , Gudmundur Johansson 6 and Irène Netchine 7   Citation: Eggermann, T.; Davies, J.H.; Tauber, M.; van den Akker, E.; Hokken-Koelega, A.; Johansson, G.; Netchine, I. Growth Restriction and Genomic Imprinting-Overlapping Phenotypes Support the Concept of an Imprinting Network. Genes 2021, 12, 585. https://doi.org/10.3390/ genes12040585 Academic Editors: Humaira Gowher, Miguel Constancia, Marika Charalambous, Ionel Sandovici and Eamonn Maher Received: 15 March 2021 Accepted: 13 April 2021 Published: 17 April 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Institute of Human Genetics, Medical Faculty, RWTH Aachen University, 52062 Aachen, Germany 2 Department of Paediatric Endocrinology, University Hospital Southampton, Southampton SO16 6YD, UK; Justin.Davies@uhs.nhs.uk 3 Research centre of rare diseases PRADORT, Childrens Hospital, CHU Toulouse, Toulouse Institute of Infectious and Inflammatory Diseases (Infinity), INSERM UMR1291-CNRS UMR5051-Tolouse III University, 31062 Toulouse, France; tauber.mt@chu-toulouse.fr 4 Erasmus University Medical Center, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands; e.l.t.vandenakker@erasmusmc.nl 5 Erasmus University Medical Center, Pediatrics, Subdivision of Endocrinology, 3015 GD Rotterdam, The Netherlands; a.hokken@erasmusmc.nl 6 Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg and Department of Endocrinology, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden; gudmundur.johannsson@medic.gu.se 7 Medical Faculty, AP-HP, Armand Trousseau Hospital-Functional Endocrine Research Unit, INSERM, Research Centre Saint-Antoine, Sorbonne University, 75012 Paris, France; irene.netchine@aphp.fr * Correspondence: teggermann@ukaachen.de; Tel.: +49-241-8088008; Fax: +49-241-8082394 Abstract: Intrauterine and postnatal growth disturbances are major clinical features of imprinting disorders, a molecularly defined group of congenital syndromes caused by molecular alterations affecting parentally imprinted genes. These genes are expressed monoallelically and in a parent-of- origin manner, and they have an impact on human growth and development. In fact, several genes with an exclusive expression from the paternal allele have been shown to promote foetal growth, whereas maternally expressed genes suppress it. The evolution of this correlation might be explained by the different interests of the maternal and paternal genomes, aiming for the conservation of maternal resources for multiple offspring versus extracting maximal maternal resources. Since not all imprinted genes in higher mammals show the same imprinting pattern in different species, the findings from animal models are not always transferable to human. Therefore, human imprinting disorders might serve as models to understand the complex regulation and interaction of imprinted loci. This knowledge is a prerequisite for the development of precise diagnostic tools and therapeutic strategies for patients affected by imprinting disorders. In this review we will specifically overview the current knowledge on imprinting disorders associated with growth retardation, and its increasing relevance in a personalised medicine direction and the need for a multidisciplinary therapeutic approach. Keywords: imprinting disorders; growth restriction; overgrowth; differentially methylated regions; imprinted gene network; Silver-Russell syndrome; transient neonatal diabetes; Prader-Willi syn- drome; temple syndrome; pseudoparahypoparathyreoidism 1. Introduction The epigenetic phenomenon of genomic imprinting allows the parent-of-origin-specific expression of only one allele of a gene in a spatial and temporal manner. From compre- hensive studies in mice, numerous imprinted genes and their biological functions were identified [1], and syntenic imprinted chromosomal regions have been determined in humans though their regulation is dynamic and variable between different species [2]. The proper setting of imprinting marks is crucial for normal developmental processes in Genes 2021, 12, 585. https://doi.org/10.3390/genes12040585 https://www.mdpi.com/journal/genes