GENETICS AND ETIOLOGY OF DOWN SYNDROME Edited by Subrata Dey Contents Preface IX Part 1 Genetics and Etiology 1 Chapter 1 Genetics of Down Syndrome 3Thomas Eggermann and Gesa Schwanitz Chapter 2 Etiology of Down Syndrome: Risk of Advanced Maternal Age and Altered Meiotic Recombination for Chromosome 21 Nondisjunction 23 Subrata Kumar Dey and Sujoy Ghosh Chapter 3 Combinatorial Gene Effects on the Neural Progenitor Pool in Down Syndrome 37 Jie Lu and Volney Sheen Chapter 4 Down Syndrome: A Complex and Interactive Genetic Disorder 65 Samantha L. Deitz, Joshua D. Blazek, Jeffrey P. Solzak and Randall J. Roper Chapter 5 Abnormal Folate Metabolism and Maternal Risk for Down Syndrome 97 Érika Cristina Pavarino, Bruna Lancia Zampieri, Joice Matos Biselli and Eny Maria Goloni Bertollo Chapter 6 Down Syndrome Expressed Protein; DSCR-1 Deters Cancer and Septic Inflammation 121 Takashi Minami Chapter 7 Down Syndrome and Vascular Disease: DSCR1 and NFAT Signaling 137 Monica Y. Lee and Brian R. Wamhoff Part 2 Down Syndrome Models 157 Chapter 8 Down Syndrome Model of Alzheimer’s Disease: Beyond Trisomy 21 Nondisjunction 159 Antoneta Granic and Huntington Potter Chapter 9 Deficiency of Adult Neurogenesis in the Ts65Dn Mouse Model of Down Syndrome 177 Pavel V. Belichenko and Alexander M. Kleschevnikov Part 3 Neurologic, Urologic, Dental and Allergic Disorders 193 Chapter 10 Dermatological Manifestations of Down Syndrome 195 Dominguez-Cruz JJ and Bueno Delgado MA Chapter 11 Down Syndrome and Periodontal Disease 209 Ahmed Khocht Chapter 12 Dysfunctional Voiding of Non-Neurogenic Neurogenic Bladder: A Urological Disorder Associated with Down Syndrome 231 Narihito Seki and Nouval Shahab Chapter 13 Down Syndrome and Epilepsy 241 A. Nascimento and C. Ortez-González Chapter 14 Endocrine and Autonomic Nervous Adaptations during Physical Exercise in Down Syndrome 259 Véronique ~ Aurélie Bricout Chapter 15 Language and Visuospatial Abilities in Down Syndrome Phenotype: A Cognitive Neuroscience Perspective 275 George Grouios and Antonia Ypsilanti Part 4 Prenatal Diagnosis and Screening 287 Chapter 16 Prenatal Diagnosis of Down Syndrome 289 Myungshin Kim, Jong Chul Shin and In Yang Park Chapter 17 First Trimester Screening for Trisomy 21 by Maternal Age, Nuchal Translucency and Fetal Nasal Bone in Unselected Pregnancies 301 Ksenija Gersak, Maja Pohar-Perme and Darija M. Strah Chapter 18 Noninvasive Prenatal Nucleic Acid Diagnostics of Down Syndrome 313 Radek Vodicka, Radek Vrtel, Jana Böhmova, Romana Kratochvilova, Ladislav Dusek, Ishraq Dhaifalah and Jiri Santavy Preface This book provides the recent developments and advances in research on Down syndrome. It also covers a wide range of topics, including investigations on neurologic, urologic, dental and allergic disorders in Down syndrome. Chromosomal aneuploidy is the leading cause of fetal death in our species and the information about chromosomal nondisjunction in man largely comes from studies in trisomy 21 or Down syndrome, the most frequent of the autosomal trisomies in liveborns. The cause of nondisjunction of chromosome 21 remains largely unknown. Accurate investigations on meiotic nondisjunction have been made possible in recent years by the development and utilization of microsatellite markers. Although several hypotheses have been put forward, it is still unclear as to whether particular gene loci on chromosome 21 are sufficient to cause Down syndrome and its associated features. For over two decades trisomy 21 has represented a prototype disorder for the study of human aneuploidy and copy-number variation, but the genes responsible for most Down syndrome phenotypes are still unknown. The genetic mechanism by which wide variability in the phenotypes arise is not understood, additional complexity may exist due to possible epigenetic changes that may act differently on Down syndrome. Consequently, gene-disease links have often been based on indirect evidence from cellular or animal models. Numerous mouse models with features reminiscent of those seen in individuals with Down syndrome have been produced and studied in some depth, and these have added considerable insight into possible genetic mechanisms by which trisomy 21 leads to Down syndrome. The book is organized into four sections. All sections include chapters on recent advances in Down syndrome research. Section I deals with our present knowledge on the genetics and etiology of Down syndrome. Section II discusses the utility of using mouse model for in depth study of Down syndrome. Down syndrome could be used as model for understanding the genetics of Alzheimer’s disease. Section III describes the etiology and clinical aspects of some common disorders of Down syndrome patients such as neurologic, urologic, dental and allergic disorders. Section IV focuses on prenatal diagnosis and screening of Down syndrome. This book provides a concise yet comprehensive source of current information on Down syndrome. Research workers, scientists, medical graduates and paediatricians will find it an excellent source for reference and review. Acknowledgements The editor wants to acknowledge the superb assistance of staff members and management of InTech Publisher. In particular, Ms. Romina Krebel for her coordination and editorial assistance. We are grateful to all contributing authors and scientists who made this book possible by providing valuable research and review papers. Subrata Dey Salt Lake City, Kolkata, India
