GENETICS

This course will provide up-to-date information on genetics and epidemiology of renal and liver tumors in children, including Wilms tumor and hepatoblastoma. We will discuss recent findings in germ-line mutations and familial associations. The course will inform the clinician of the emerging association of hepatoblastoma and premature and low-birth weight infants and introduce strategies for cancer surveillance in the high-risk child.

Genetics of Wilms Tumor
Max J. Coppes, Alberta Children's Hospital, Alberta, Canada

Cytogenetics of Renal and Liver Tumors in Children
Nancy R. Schneider, University of Texas Southwestern Medical Center, Dallas, TX

Cancer Surveillance for Overgrowth Syndromes
Michael R. DeBaun, Washington University School of Medicine, St. Louis, MO

This 3-hour mini-course will update primary and subspecialty care providers on the advances in our understanding of von Willebrand Disease, the most common inherited bleeding disorder. The minicourse will provide an overview of both basic and clinical aspects of this disease, including discussion of the biochemistry and genetics of von Willebrand Factor, dilemmas in the diagnosis of this highly variable disease, and advances in the management of children and adolescents with von Willebrand Disease. Congenital platelet function abnormalities, which share clinical similarities with von Willebrand Disease, will also be discussed.

Overview
Sara J. Israels, University of Manitoba, Winnipeg, Canada

The Biology and Molecular Genetics of von Willebrand Factor and von Willebrand Disease
J. Evan Sadler, Howard Hughes Medical Institute and Washington University School of Medicine, St Louis, MO

Approach to the Diagnosis of von Willebrand Disease
Robert R. Montgomery, Medical College of Wisconsin and the Blood Research Institute of the Blood Center, Milwaukee, WI

Break

Management of Children and Adolescents with von Willebrand Disease
Donna DiMichele, New York Presbyterian Hospital/Weill Medical College of Cornell University, New York, NY

Approaches to the diagnosis, prevention, and treatment of chronic conditions in childhood and adolescence have changed greatly with greater survival of most children, even with severe conditions. Thus, for most children, new issues include preparation for adulthood rather than expectation of early death. Community pediatricians have increasing numbers of children with chronic conditions in their practices and thereby face new challenges in the care of these children and their families. Advances in molecular biology and genetics will lead to more effective ways to identify and treat many conditions. At the same time, children and adolescents face a great rise in new epidemics of chronic conditions, with marked increases in obesity, asthma, Type 2 diabetes, mental health conditions (especially ADHD and depression). This session will examine new advances in the biology of chronic conditions, important changes in epidemiology, consideration of important outcomes for children and adolescents with chronic conditions, and new efforts to improve their pediatric care.

Overview

New Morbidities: Clinical and Social Changes in Childhood Chronic Conditions
James M. Perrin, Mass General Hospital for Children, Harvard Medical School, Boston, MA

Prospects for New Treatments
Alan B. Ezekowitz, Massachusetts General Hospital, Boston, MA

Improving the Care of Children with Chronic Illness
Carole M. Lannon, AAP liaison, National Initiative for Children's Helathcare Quality, University of North Carolina, Chapel Hill, NC

Outcomes of Chronic Conditions: What Should We Measure?
Ruth E. K. Stein, Albert Einstein College of Medicine/Children's Hospital of Montefiore, Bronx, NY

This minicourse will highlight new technologies in genetics and genomics that build on the mapping and sequencing of human and model organism genomes to define the function of genes and their clinical importance in normal health and disease.

Genetic Analysis of Hematopoiesis and Cancer
Leonard I. Zon, Howard Hughes Medical Institute, Children's Hospital, Boston, MA

Genetic Polymorphisms for Linkage and Association Studies
Aravinda Chakravarti, Johns Hopkins University School of Medicine, Baltimore, MD

Gene Expression: Expression Profiling and Microarray Technology
Jeffrey M. Trent, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD

As we entered the molecular genetics era, the hope had been that correlation of mutations with clinical course would permit accurate prediction of prognosis with future patients. However, as increasing information has been accumulated, what has emerged has been the recognition that clinical variability among individuals with identical mutations is the rule, not the exception. We will explore mechanisms for clinical variability, including protein activity, thresholds, modifier genes, and system complexity.

Complexity of Single Gene Disorders
Edward R. B. McCabe, University of California School of Medicine, Los Angeles, CA

Even PKU Is Not a Simple Mendelian Disorder
Charles R. Scriver, McGill University, Montreal, PQ, Canada

Genetic Heterogeneity in CF
Garry R. Cutting, Johns Hopkins University, Institute of Genetic Medicine, Baltimore, MD

Muscle Diseases as Models of Complexity
Georgirene D. Vladutiu, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Children's Hospital, Buffalo, NY

Steroid-resistant nephrotic syndrome is one of the most common forms of primary nephrotic syndrome in childhood. Recent genetic and molecular studies indicate that the podocyte plays a central role in the pathogenesis of this disorder. This symposium will address recent advances in our understanding of the development, cell biology, and pathology of the glomerular podocyte. The recent identification of NPHS2, the gene encoding the glomerular protein podocin, and its role in autosomal recessive steroid-resistant nephrotic syndrome will be discussed. Finally, new strategies for therapeutic intervention in steroid-resistant nephrotic syndrome will be described.

Development of the Glomerular Capillary Wall
Dale R. Abrahamson, University of Kansas Medical Center, Kansas City, KS

Cell Biology and Pathology of Podocytes
Peter Mundel, Albert Einstein College of Medicine, Bronx, NY

The Genetic Basis of Steroid-Resistant Nephrotic Syndrome
Corinne Antignac, INSERM, Paris, France

Advances in molecular genetics, in our understanding of the origin of metabolic diseases and in imaging techniques are all having a major impact on perinatal medicine. The role of these new insights and interventions is no greater anywhere than their impact on the care of the fetus. This symposium will review these advances from the point of "The Fetus as the Patient." We will present new data demonstrating maternal-fetal chimerism and the role of this phenomenon in various pathobiologies. Advanced fetoscopic imaging techniques and the ways they can support new fetal therapies will be presented. Molecular diagnosis of genetic metabolic disorders can now be made prenatally to allow earlier fetal treatment and improvement in outcomes.

Overview
James F. Padbury, Women & Infants Hospital of Rhode Island, Brown University, Providence, RI

Bidirectional Feto-Maternal Cell Trafficking: Relevance for Pediatric and Adult Disorders
Diana W. Bianchi, Tufts University, New England Medical Center, Boston, MA

Fetal Surgery: In Praise of Tunnel Vision
Francois Luks, Brown University School of Medicine, Rhode Island Hospital, Hasbro Children's Hospital, Providence, RI

Genetic Metabolic Disorders: Current Status of Prenatal Diagnosis and Treatment
Mark Korson, Tufts University, New England Medical Center, Boston, MA

Discussion

This symposium will address a topic of considerable public debate, especially as it relates to research involving human subjects, among these clinical trials using children as subjects, and research involving gene therapy. A recent two-day meeting at NIH was devoted to this subject and it is likely that there will be new and more explicit guidelines promulgated by HHS. The symposium will address these issues from the perspective of academic pediatrics and pediatric research, in particular with regard to the impact on education at both the undergraduate and graduate levels and the availability of appropriate tests and therapies for children. The role of professional societies, such as the sponsoring members of the PAS meeting, will be examined. The symposium is planned to allow at least 30 minutes of interactive discussion between the members of the panel and the audience.

This session will provide important new mechanistic information about the maternal, placental and fetal influences on certain adult onset diseases. Investigators undertaking studies that are on the cutting edge will provide an overview and share some of their recent experimental results during this session. The first lecture will concentrate on maternal health and its role on adult onset diseases; the second lecture will delineate the role of placental factors; while the third session will detail fetal origins of adult hypertensive disease.

Overview
Sherin U. Devaskar, Mattel Children's Hospital, University of California, Los Angeles, CA

Maternal Health and Its Influence on Adult Onset Diseases
Judith G. Hall, University of British Columbia, Vancouver, Canada

The Placenta Dilemma
Susan Fisher, University of California, San Francisco, CA

Fetal Origins of Adult Hypertension
Susan Bagby, Oregon Health Sciences University, Portland, OR

Discussion

This session focuses on the developmental biology of hematopoiesis, utilizing the zebrafish as a genetic model. The focus of research over the next few years, described in this session, will be to understand stem cell biology, particularly focusing on the induction and self-renewal of the hematopoietic stem cell. Through the analysis of these newly derived mutant genes and cell biology, the hope is to develop a better understanding of stem cell plasticity. The fields of stem cell biology and cancer biology are likely to merge as we understand more about cell differentiation and proliferation during development.

Overview
Jeffrey M. Lipton, Schneider Children's Hospital, New Hyde Park, NY

Hematopoietic Stem Cell Development in Zebrafish
Leonard I. Zon, Howard Hughes Medical Institute, Children's Hospital, Boston, MA

Advances in Stem Cell Biology
Ron McKay, National Institutes of Health, Bethesda, MD

Hormones regulate critical biological functions including neurologic growth, sexual differentiation, and organ maturation, through intricate signaling mechanisms. Pregnant women, infants, and children are increasingly exposed to chemicals in the environment that mimic or block hormones, often at very small doses. Exposure to these endocrine disruptors occurs at home, in the workplace and the community, and even as a consequence of medical care. This session will review the growing evidence of adverse health effects due to exposure to endocrine disruptors and discuss new research efforts that will help fill in the gaps in our knowledge in this area.

Overview
Philip John Landrigan, Center for Children's Health & the Environment, Mt. Sinai School of Medicine, New York, NY

Evidence of Endocrine Disruption: Lessons from Wildlife
Louis Guillette, University of Florida, Gainesville, FL, University of Florida, Gainesville, FL

NHANES: A Rich Source of National Pediatric and Adolescent Exposure Data
Elaine Gunter, NHANES Laboratory, Centers for Disease Control & Prevention, Atlanta, GA

Biomarkers in Endocrine Disruptor Research
Cynthia F. Bearer, Case Western Reserve University, Cleveland, OH

Discussion

The diagnosis and treatment of H. pylori in children is a controversy surrounded with questions of who should be tested, what are the most reliable tests, who should be treated, and what is the preferred therapy. A panel of experts will examine the epidemiology and clinical outcomes of infection, microbial and host factors, and the newly published clinical practice guidelines from the North American Society for Pediatric Gastroenterology and Nutrition.

Overview
Benjamin D. Gold, Associate Professor of Pediatrics and Microbiology, Emory University School of Medicine, Atlanta, GA

Epidemiology and Clinical Outcomes of Infection
John D. Snyder, Professor of Pediatrics, University of California Medical Center, San Francisco, CA

Microbial Genome and Virulence Determinants
Philip M. Sherman, Professor of Paediatrics and Microbiology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

Host Responses as Determinants of Disease Outcome
Sheila Crowe, Associate Professor of Medicine, University of Texas Medical Branch, Galveston, TX

NASPGN Clinical Practice Guideline Summary and Recommendations
Steven J. Czinn, Director, Division of Pediatric Gastroenterology and Nutrition, Rainbow Babies and Children's Hospital, Case Western Reserve University, Cleveland, OH

The Human Genome Project is impacting every aspect of medicine. Dr. Craig Venter, President of Celera Genomics, one of the chief architects of this venture, will discuss the accomplishments of the human genome project and implications for future impact on health and disease in this special one-hour state of the art lecture.

Sequencing the Human Genome
J. Craig Venter, President, Celera Genomics, Rockville, MD

Supported in part by an educational grant from the Columbus Children's Hospital, Columbus, OH

Advances in molecular genetics and high through-put analytical chemistry like tandem mass spectrometry (MS/MS) are enabling technologies that permit expanded newborn screening for presymptomic diagnosis of disorders not previously feasible. The prototype genetic disease for which newborn screening is now available is cystic fibrosis. The group of metabolic diseases that can now be diagnosed by MS/MS includes medium chain acyl-CoA dehydrogenase (MCAD) deficiency and related disorders of fatty acid oxidation. This symposium will address the issue of whether these diseases should be added to expanded newborn screening profiles. If so, what is the sensitivity and specificity of the currently available tests? If included in expanded screening programs, who should do the testing and how? What are the implications for genetic counseling? Should any of the new approaches be adapted to preconceptual testing? What important policy issues are created by this new capacity? There is substantial variation among states currently on screening programs. Should there be national guidelines? Who should decide about expanded screening? How will these new tests be paid and by whom?

Overview
James F. Padbury, Women & Infants Hospital of Rhode Island, Brown University, Providence, RI

Newborn Screening for Cystic Fibrosis: An Opportunity To Give Every CF Patient a Healthy Start
Philip M. Farrell, Dean and Alfred Dorrance Daniels Professor on Diseases of Children, University of Wisconsin Medical School, Madison, WI

Tandem Mass Spectrometry and Expanded Newborn Screening
Charles R. Roe, Medical Director, Institute of Metabolic Diseases, Baylor University Medical Center, Dallas, TX

Public Policy Issues in Expanded Newborn Screening
Bradford L. Therrell, Director and Professor, National Newborn Screening and Genetics Resource Center, University of Texas Health Science Center, San Antonio, TX

The roles of nature and nurture in shaping behavior are complex and our understanding of them is constantly expanding. Exciting recent findings have given us new perspectives on biologic influences on brain functioning and subsequent behavior. Genetic conditions can be reflected in clearly identifiable behavioral phenotypes. Prenatal exposure to nicotine can have effects that are measurable in adolescence, and low level exposure to environmental toxins are impacting cognitive and behavioral functioning of the current generation. Three outstanding speakers will discuss these advances in our knowledge of neuroscience and their implications for the identification and treatment of a variety of neurodevelopmental conditions.

Overview
Daniel Lee Coury, Children's Hospital, Columbus, OH

Fragile X Syndrome: A Model of Gene-Brain Behavior Relationships
Randi J. Hagerman, University of California at Davis Medical Center, Sacramento, CA

Tobacco, Nicotine and Fetal Brain Damage: The Smoking Gun in ADHD and SIDS
Theodore Slotkin, Duke University Medical Center, Durham, NC

Neurotoxicity of Low-Level Exposure to Pesticides and PCBs
Philip John Landrigan, Center for Children's Health & the Environment, Mt. Sinai School of Medicine, New York, NY

The role of experience and the environment in early child development has long been appreciated, but it has been likened to loading software on a computer.  Recent research in neurobiology suggests that early experiences are not only loading software but actually changing the hard wiring of the brain.  Many of the brain’s pathways are in place by three years of age.  What are the implications for this research?  Do these pathways continue to change and evolve with experience? What are the effects of early insults on brain development? This program will focus on the Institute of Medicine Report From "Neurons to Neighborhoods".  The speakers will focus on what is known about the neurobiology of brain development and the implications this research has on child development programs.  The session will highlight how the current knowledge of brain development will impact future research as well as how it may translate into public policy.

Overview
Barry S. Zuckerman, Boston University School of Medicine, Boston, MA

The Critical Period Viewpoint and a More Complete View of the Effects of Experience on the Brain
William Greenough, University of Illinois College of Medicine, Chicago, IL

Early Biologic Insults on Brain Development
Betsy Lozoff, University of Michigan, Ann Arbor, MI

Neurons to Neighborhood: Translating the Science to Policy and Program
Deborah Phillips, Georgetown University, Washington, DC

Discussion