Emery and Rimoin's Principles and Practice of Medical Genetics and Genomics Clinical Principles and Applications SEVENTH EDITION Editors Reed E. Pyeritz Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States Bruce R. Korf University of Alabama at Birmingham, Birmingham, AL, United States Wayne W. Grody UCLA School of Medicine, Los Angeles, CA, United States Table of Contents Cover image Title page Copyright List of Contributors Preface to the Seventh Edition of Emery and Rimoin’s Principles and Practice of Medical Genetics and Genomics Preface to Clinical Principles and Applications 1. A Clinical Approach to the Dysmorphic Child 1.1. Introduction 1.2. Prenatal Versus Postnatal Onset of Developmental Problems 1.3. Prenatal-Onset Problems in Development 1.4. Postnatal-Onset Problems in Development 1.5. Conclusion 2. Clinical Teratology 2.1. Introduction 2.2. Evaluating the Patient and Her Exposure 2.3. Recognized Teratogenic Exposures 2.4. Paternal Exposures and Maternal Exposures Before or Shortly After Conception 2.5. Future Perspective 2.6. Conclusion 3. Neurodevelopmental Disabilities: Global Developmental Delay, Intellectual Disability, and Autism 3.1. Intellectual Disability and Global Developmental Delay 3.2. Global Developmental Delay 3.3. Definition of a Diagnosis 3.4. Whole Exome Sequencing 3.5. Whole Genome Sequencing 3.6. Phenotyping 3.7. Genetic Mechanisms of ID 3.8. Diagnostic Testing of Patients With ID of Unknown Cause 3.9. Cytogenomic Copy Number Abnormalities 3.10. X-Linked ID 3.11. Fragile X Syndrome 3.12. Autism Spectrum Disorders 3.13. Inborn Errors of Metabolism and ID 3.14. CNS Malformations, Intellectual Disability and Brain Imaging 3.15. Summary 4. Abnormal Body Size and Proportion Glossary 4.1. Introduction 4.2. Approach to the Patient With Abnormal Stature 4.3. Mechanisms of Growth 4.4. Pathologic Short Stature 4.5. Pathologic Overgrowth 4.6. Conclusion Chapter 5. Cytogenetic Analysis 5.1. Introduction 5.2. Milestones in Human Cytogenetics 5.3. Indications for Cytogenetic Analysis 5.4. Tissue Samples and Cell Culture 5.5. Chromosome Banding 5.6. Normal Human Karyotype 5.7. Chromosome Abnormalities 5.8. In Situ Hybridization 6. Diagnostic Molecular Genetics 6.1. Introduction 6.2. Indications for Molecular Genetic Testing 6.3. Technical Approaches to Molecular Genetic Testing 6.4. Molecular Genetic Diagnosis of Some Commonly Tested Diseases 6.5. Mitochondrial DNA Disorders 6.6. Other Targets of Molecular Genetic Screening 6.7. Pharmacogenetic Testing 6.8. Quality Assurance, Reimbursement, and Regulatory Issues 6.9. Internet Resources for Molecular Genetic Testing 6.10. Societal Impact of the New Genetic Technology 6.11. Future Directions 7. Therapies for Lysosomal Storage Diseases 7.1. Introduction 7.2. Enzyme Replacement Therapy 7.3. Bone Marrow Transplantation 7.4. Substrate Reduction Therapy 7.5. Pharmacologic Chaperone Therapy 7.6. Emerging Therapies: Gene Therapy and Genome Editing 8. Transplantation Genetics 8.1. The Major Histocompatibility Complex 8.2. Historical Iter Toward Histocompatibility Definition 8.3. Currently Most Used Methods for HLA Typing 8.4. Clinical Significance of HLA Molecular Typing 8.5. Stem Cells and Transplantation 8.6. Concluding Remarks 9. Genetic Evaluation for Common, Chronic Disorders of Adulthood 9.1. Background 9.2. Outcomes of Genetic Services 9.3. The Process of Genetic Consultation for Common, Chronic Diseases of Adulthood 9.4. Genetic Healthcare Models Summary 10. Carrier Screening and Heterozygote Testing Glossary 10.1. Introduction 10.2. Carrier Screening in Clinical Practice 10.3. Carrier Screening in Individuals of Defined Subpopulation Groups 10.4. Therapeutic Implications for Heterozygotes 10.5. Sensitivity and Specificity 10.6. Cost and Feasibility 10.7. Genetic Counseling and Informed Consent 10.8. Conclusions 11. Circadian Rhythms and Disease 11.1. Introduction 11.2. Molecular Mechanisms 11.3. Central and Peripheral Clocks 11.4. Circadian Diseases 11.5. Metabolic and Cardiovascular Disorders 11.6. Cancer 11.7. Psychologic and Neurologic Diseases and Circadian Rhythms 11.8. Chronotherapy 11.9. Concluding Remarks 12. The Genomic Health Record: Current Status and Vision for the Future 12.1. Introduction 12.2. Conclusion 13. Ethical and Social Issues in Clinical Genetics 13.1. Introduction 13.2. The Historical Context 13.3. Genetic Counseling, Testing, and Screening 13.4. Diagnostic Genetic Testing 13.5. Predictive Genetic Testing 13.6. Confidentiality 13.7. Genetic Testing in Childhood 13.8. Population Genetic Screening 13.9. Other Challenges in Genetic Counseling 14. Genetics and Genomics in Public Health 14.1. What Is Public Health Genetics/Genomics? 14.2. The Purposes of Public Health 14.3. The Public Health System Infrastructure 14.4. Evolution and Convergence of Two Fields of Science— Public Health and Genetics/Genomics 14.5. Future Direction for Public Health Genetics/Genomics 15. Implementation of Genomic Medicine: An International Perspective 15.1. Introduction 15.2. Large-Scale Genomic Medicine Initiatives 15.3. National Genomic Medicine Initiatives 15.4. Large-Scale Regional Genome Initiatives 15.5. Corporate Genomic Medicine Initiatives 15.6. Studying Founder Populations 15.7. Conclusions and Future Perspectives 15.8. Competing Interests Index