Molecular Genetics of Pediatric Orthopaedic Disorders PDF
Preview Molecular Genetics of Pediatric Orthopaedic Disorders
Molecular Genetics of Pediatric Orthopaedic Disorders Carol A. Wise • Jonathan J. Rios Editors Molecular Genetics of Pediatric Orthopaedic Disorders 2123 Editors Carol A. Wise Jonathan J. Rios Sarah M. and Charles E. Seay Center for Sarah M. and Charles E. Seay Center for Musculoskeletal Research Musculoskeletal Research Texas Scottish Rite Hospital for Children Texas Scottish Rite Hospital for Children Dallas Dallas Texas Texas USA USA ISBN 978-1-4939-2168-3 ISBN 978-1-4939-2169-0 (eBook) DOI 10.1007/978-1-4939-2169-0 Library of Congress Control Number: 2015930329 Springer New York Heidelberg Dordrecht London © Springer Science+Business Media New York 2015 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) The editors thank the patients and families with pediatric orthopaedic disorders who have participated in research studies and furthered our understanding of their conditions. Preface Pediatric orthopaedic practice typically centers around a diverse array of heritable disorders. At one extreme end of the heritability spectrum are completely penetrant Mendelian disorders such as brachydactyly, where unaffected parents never have affected offspring. Described by Farabee in 1905, brachydactyly was the first pub- lished description of autosomal dominant inheritance of a human malformation (1). Even earlier, however, Galton described the concept of traits such as height that, although often lacking a clear transmission pattern in families, are still heritable to some degree (2). We of course now appreciate that there are significant genetic underpinnings in many non-traumatic childhood orthopaedic disorders, such as idiopathic scoliosis and talipes equinovarus (clubfoot), and that the care of such complex diseases typically represents the majority of pediatric orthopaedic practice. Finally, at the other extreme of the heritability spectrum is the startling discovery that completely non-heritable malformations such as macrodactyly, paradoxically, have genetic origins. Disease gene discovery for these disorders began, for all prac- tical purposes, in the late 1980’s and has since moved ahead with dizzying speed, driven in large part by technological advances. Such discoveries are enabling a new biochemical understanding of disease processes and, more importantly, informing the design of new treatments, as for example therapies that target the signaling path- ways causing the troubling manifestations in neurofibromatosis (3). The purpose of this volume is to update the pediatric orthopaedic community— clinicians, surgeons, geneticists, and researchers—on recent genetic developments relevant to the diverse presentations in these patients. We begin with an introduction to “next-generation” technologies that are enabling rapid gene discovery. We also present chapters describing post-gene discovery advancements for neurofibromato- sis, various disorders of the joints, and basic bone development. Almost half of the volume is devoted to the complex disorders scoliosis and clubfoot and describes their classification, genetic contributions, and the exciting breakthrough in under- standing genetic and environmental interactions. Finally we present the very recent discoveries of the mutations causing somatic, non-heritable, and all too devastating overgrowth malformations. New insights into each of these areas are no doubt waiting in the wings, given the pace of discovery today. Our goal in this volume is to provide pediatric clinicians, vii viii Preface surgeons, geneticists, and researchers with a resource for understanding these emerging new developments as a means to advance the care of affected children. References 1. Farabee. Inheritance of digital malformations in man. Papers of the peabody museum for American archeology and ethnology. (Harvard University) 1905;3:69. 2. Galton F. Hereditary talent and character. Macmillan’s Mag. 1865;12:157. 3. Kalamarides MI, Acosta MT, Babovic-Vuksanovic D, Carpen O, Cichowski K, Evans DG, Giancotti F, Hanemann CO, Ingram D, Lloyd AC, Mayes DA, Messiaen L, Morrison H, North K, Packer R, Pan D, Stemmer-Rachamimov A, Upadhyaya M, Viskochil D, Wallace MR, Hunter-Schaedle K, Ratner N. Neurofibromatosis 2011: a report of the children’s tumor foun- dation annual meeting. Acta Neuropathol. 2012;123(3):369–80. Contents 1 Overview of Next Generation, High-Throughput Molecular Genetic Methods ......................................................................................... 1 Jonathan J. Rios 2 N eurofibromin in Skeletal Development .................................................. 17 Mateusz Kolanczyk and David A. Stevenson 3 Molecular Genetics of Congenital Multiple Large Joint Dislocation .... 39 Stephen P. Robertson 4 DMP-1 in Postnatal Bone Development ................................................... 57 Shuxian Lin and Jerry Jian Q. Feng 5 The Genetic Architecture of Idiopathic Scoliosis .................................... 71 Carol A. Wise 6 Insights into the Genetics of Clubfoot ...................................................... 91 Katelyn S. Weymouth, Susan H. Blanton and Jacqueline T. Hecht 7 Classification and Etiologic Dissection of Vertebral Segmentation Anomalies ........................................................................... 105 Peter D. Turnpenny 8 Genetic and Environmental Interaction in Malformation of the Vertebral Column ............................................................................ 131 Sally L. Dunwoodie and Duncan B. Sparrow 9 Somatic Mutations in Overgrowth Syndromes ....................................... 153 Jonathan J. Rios and Marybeth Ezaki Index .................................................................................................................. 167 ix Contributors Susan H. Blanton Department of Human Genetics, University of Miami, Miami, FL, USA Sally L. Dunwoodie Developmental and Stem Cell Biology, Victor Chang Cardiac Research Institute, Sydney, NSW, Australia Marybeth Ezaki Department of Orthopaedics, Texas Scottish Rite Hospital for Children, Dallas, TX, USA Jerry Jian Q. Feng Biomedical Sciences, Baylor College of Dentistry, Dallas, TX, USA Jacqueline T. Hecht Department of Pediatrics, University of Texas Health Science Center—Medical School and School of Dentistry, Houston, TX, USA Mateusz Kolanczyk Campus Virchow Institut für Medizinische Genetik und Humangenetik, Neurofibromin in Skeletal Development, Charité Universitätsmedizin, Berlin, Germany Shuxian Lin Biomedical Sciences, Baylor College of Dentistry, Dallas, TX, USA Jonathan J. Rios Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Texas Scottish Rite Hospital for Children, Dallas, TX, USA Stephen P. Robertson Department of Women’s and Children’s Health, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand Duncan B. Sparrow Developmental and Stem Cell Biology, Victor Chang Cardiac Research Institute, Sydney, NSW, Australia David A. Stevenson Department of Pediatrics, Division of Medical Genetics, University of Utah, Salt Lake City, UT, USA Peter D. Turnpenny Clinical Genetics, Royal Devon & Exeter Hospital, Exeter, UK Katelyn S. Weymouth Department of Pediatrics, University of Texas Medical School, Houston, TX, USA xi xii Contributors Carol A. Wise Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Texas Scottish Rite Hospital for Children, Dallas, TX, USA Departments of Orthopaedic Surgery, Pediatrics, and McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, USA
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