Emery and Rimoin's Principles and Practice of Medical Genetics

Emery and Rimoin's Principles and Practice of Medical Genetics

6th Edition - February 28, 2013

Write a review

  • Editors: David Rimoin, Reed Pyeritz, Bruce Korf
  • eBook ISBN: 9780123838353

Purchase options

Purchase options
DRM-free (Mobi, PDF, EPub)
Sales tax will be calculated at check-out

Institutional Subscription

Free Global Shipping
No minimum order

Description

For decades, Emery and Rimoin’s Principles and Practice of Medical Genetics has provided the ultimate source for practicing clinicians to learn how the study of genetics can be integrated into practice. With almost 5,000 pages of detailed coverage, this fully online sixth edition of the classic reference adds the latest information on prenatal diagnosis, genetic screening, genetic counseling, and treatment strategies to complete its coverage of the growing field for medical students, residents and physicians involved in the care of patients with genetic conditions. Clinically oriented information is supported by expanded sections on basic principles of genetics, research approaches, and analytics to embrace the evolving population of students, researchers, and practitioners who are integrating their work to provide advanced diagnosis, prevention and treatment of human disease. With advances in high-throughput technologies propelling the closer integration of lab and clinical work, this edition bridges the gap between high-level molecular genetics and clinical application.

Key Features

  • Features 174 review-length contributions that encompass traditional and new areas of the field - including in cancer genetics, genomic technologies, and molecular assays
  • Provides many thousands of pertinent literature references guiding the reader in identifying related topics
  • Fully illustrated with hundreds of color images, supporting identification, concept illustration and method processing

Readership

Medical and research libraries and institutions serving researchers of human genetics/genomics; cancer, neuroscience, metabolic, endocrinology, pharmacology, behaviour, immunology, hematology, orthopaedic, pediatric, gene therapy researchers; advanced students, specialists, and medical practitioners across medical disciplines as well systems biology, molecular medicine, and genetic epidemiology.

Table of Contents

  • Preface

    Foreword

    Personal Memories of David Rimoin

    Basic Principles

    Chapter 1. History of Medical Genetics

    1.1 Preface (Peter Harper)

    1.2 Introduction

    1.3 Foundations of Medical Genetics Before 1956

    1.4 Growth and Development of Medical Genetics: 1956 to the Present

    1.5 The Future

    1.6 Addendum (PSH)

    1.7 A Timeline for Medical Genetics

    References

    Further Reading

    Chapter 2. Medicine in a Genetic Context

    2.1 Introduction

    2.2 The Principles of Disease

    2.3 Defining Disease

    2.4 The How Questions

    2.6 The Why Questions

    2.7 Prevention and Treatment

    2.8 Conclusion

    References

    Chapter 3. Nature and Frequency of Genetic Disease

    3.1 Introduction

    3.2 Frequency of Genetic Disease

    3.2.2 Single-Gene Disorders

    3.2.3 Multifactorial Disorders

    3.2.4 Somatic Cell Genetic Disorders

    3.3 Morbidity and Mortality Due to Genetic Disease

    References

    Chapter 4. Genomics and Proteomics

    4.1 Genes and Human Disease

    4.2 Genomics

    4.3 Mapping the Human Genome

    4.4 Sequencing the Human Genome

    4.5 Current Apporaches to Sequence Parts or the Whole Human Genome

    4.6 An Approach for Cloning Human Disease Genes

    4.7 Sequence-Based Methods for Detecting Chromosomal Abnormalities

    4.8 Proteomics

    Glossary

    References

    Chapter 5. Genome and Gene Structure

    5.1 Introduction

    5.2 Double Helix Structure, DNA Replication, Transcription, and Meiotic Recombination

    5.3 Organization of Genomic DNA

    5.4 Gene Structure and the Molecular Pathway of Gene Expression

    References

    Chapter 6. Epigenetics

    6.1 Introduction

    6.2 Epigenetic Mechanisms: Chromatin, DNA Methylation and Long Noncoding RNAs

    6.3 Epigenetic Reprogramming

    6.4 Epigenetic Regulation of X Inactivation

    6.5 Genomic Imprinting

    6.6 Genetic Disorders Due to Genes Affecting Chromatin Structure

    6.7 Methods For Studying Epigenetic Marks

    6.8 Cancer Epigenetics

    6.9 Environmental Influences on Epigenetic Traits

    6.10 Abnormalities in Epigenetic Programming Linked to Infertility and Assisted Reproduction

    6.11 In Utero Epigenetic Programming of Adult Traits and Disease

    6.12 Genetic–Epigenetic Interactions

    6.13 The Future: Epigenomics

    References

    Websites

    Chapter 7. Human Gene Mutation in Inherited Disease: Molecular Mechanisms and Clinical Consequences

    7.1 Introduction

    7.2 Molecular Mechanisms of Mutation Causing Human Inherited Disease

    7.3 Disease-Causing Mutations

    7.4 Consequences of Mutations

    7.5 General Principles of Genotype–Phenotype Correlations

    7.6 Why Study Mutation?

    Acknowledgments

    References

    Further Reading

    Chapter 8. Genes in Families

    8.1 Introduction

    8.2 Pedigree Construction

    8.3 Unifactorial Inheritance/Single-Gene Disorders

    8.4 Dominance and Recessiveness

    8.5 Autosomal-Dominant Inheritance

    8.6 Autosomal Recessive Inheritance

    8.7 Sex-Linked Inheritance

    8.8 X-Linked Recessive Inheritance

    8.9 X-Linked Dominant Inheritance

    8.10 Y-Linked (Holandric) Inheritance

    8.11 Partial Sex Linkage

    Cross References

    References

    Chapter 9. Analysis of Genetic Linkage

    9.1 Introduction to Linkage Analysis

    9.2 Linkage Analysis: Basic Concepts

    9.3 Extending Parametric Linkage Analysis

    9.4 Linkage Analysis for Complex and Quantitative Traits

    9.5 Linkage Analysis: Future Directions

    Web pages for Linkage Analysis Software are listed in Tables 9-1 and 9-2.

    Additional Web Pages

    Further Reading

    Chapter 10. Chromosomal Basis of Inheritance

    10.1 Introduction

    10.2 Chromosome Structure

    10.3 Chromosomes in Cell Division

    10.4 Methods for Studying Human Chromosomes

    10.5 Functional Organization of Chromosomes

    10.6 Sex Chromosomes and Sex Determination

    10.7 Uniparental Disomy and Imprinting

    10.8 Chromosome Abnormalities

    10.9 Concluding Remarks

    Glossary

    References

    Chapter 11. Mitochondrial Medicine: The Mitochondrial Biology and Genetics of Metabolic and Degenerative Diseases, Cancer, and Aging

    Abbreviations

    11.1 Mitochondrial Biology and Genetics

    11.2 Inherited nDNA Mitochondrial Diseases

    11.3 Mitochondrial Etiology for Common Metabolic and Visceral Diseases

    11.4 Mitochondrial Etiology for Neurodegenerative Diseases

    11.5 Mitochondrial Defects in Cancer

    11.6 Therapeutic Approaches to Mitochondrial Disease

    11.7 A Mitochondrial Paradigm for Complex Disease

    Acknowledgments

    Cross References

    References

    Websites Cited

    Further Reading

    Chapter 12. Multifactorial Inheritance and Complex Diseases

    12.1 Introduction

    12.2 Definitions and Terminology

    12.3 Determining the Genetic Component of a Trait

    12.4 The International HapMap Project

    12.5 Genome-Wide Association Studies

    12.6 Association Methods/Statistical Analysis

    12.7 Analysis of Rare Variants Using New Technologies

    12.8 Integration of Genetic, Genomic, and Functional Data for Analysis of Multifactorial Diseases

    12.9 Conclusions

    References

    Chapter 13. Population Genetics

    13.1 Introduction

    13.2 Hardy–Weinberg Law

    13.3 Factors That Affect Hardy–Weinberg Equilibrium

    13.4 Applications in Population Genetics

    References

    Relevant Websites

    Further Reading

    Chapter 14. Pathogenetics of Disease

    14.1 Introduction

    14.2 The Scope of Abnormal Phenotypes: Disease and Malformation

    14.3 Physiologic Homeostasis

    14.4 Multivariate Normal Distributions and the Threshold Model

    14.5 Ontogenesis of Anatomic Structures: Angular Homeostasis

    14.6 Pathogenetics of Refined Traits

    14.7 Pathways and Multiple-Stage Processes

    14.8 Molecular Pathogenetics

    14.9 Conclusions

    Acknowledgments

    Cross References

    References

    Chapter 15. Human Developmental Genetics

    15.1 Introduction and Overview

    15.2 Timing of Normal Human Development

    15.3 The Concept of Developmental Fields and Field Defects

    15.4 Cellular Signaling in Development: The Concepts of Induction and Competence

    15.5 A Limited Repertoire of Developmental Genes and Pathways

    15.6 Steps and Concepts in Embryonic Development

    15.7 Regulation of Gene Expression in Development

    15.8 Developmental Gene Pathways and Families

    15.9 Organogenesis

    15.10 Conclusion

    References

    Chapter 16. Twins and Twinning

    16.1 Introduction

    16.2 Determining Zygosity

    16.3 Incidence of Twins

    16.4 Vanishing Twin

    16.5 Structural Defects in Twins

    16.6 Twins in Genetic Studies

    16.7 Dizygotic Twins

    16.8 Monozygotic Twins

    16.9 Conclusions

    Permissions

    Cross References

    References

    Chapter 17. The Molecular Biology of Cancer

    17.1 Introduction

    17.2 A Genetic Basis of Cancer

    17.3 Viral Oncogenes

    17.4 Oncogenic Alleles in Human Cancers

    17.5 Tumor Suppressor Genes

    17.6 The Role of DNA Damage Repair Genes in Inherited Cancer Syndromes

    References

    Chapter 18. The Biological Basis of Aging: Implications for Medical Genetics

    18.1 Introduction

    18.2 What is Aging?

    18.3 Why do we Age?

    18.4 How do we Age?

    18.5 Progeroid Syndromes of Humans

    18.5.3 Human Allelic Variants Homologous to Pro-Longevity Genes in Model Organisms

    References

    Chapter 19. Pharmacogenetics and Pharmacogenomics

    19.1 Introduction

    19.2 Fundamental Aspects of Clinical Pharmacology

    19.3 Classical Genetics and Pharmacogenetics: 1900 to Approximately 1990

    19.4 Ethnic Differences in Gene–Drug Interactions

    19.5 Pharmacogenomics

    19.6 Conclusions

    Acknowledgments

    References

    Further Reading

    General Principles

    Chapter 20. Genetic Evaluation for Common Diseases of Adulthood

    20.1 Background

    20.2 The Process of Genetic Evaluation for Common Diseases

    20.3 Integrating Genetic Information into Routine Clinical Practice

    20.4 Summary

    References

    Chapter 21. Genetic Counseling and Clinical Risk Assessment

    21.1 What Is Genetic Counseling?

    21.2 Process of Genetic Counseling

    21.3 Adult-Onset Disorders

    21.4 Genetic Risk Assessment and Calculation in the Clinical Setting

    Acknowledgments

    Cross References

    References

    Further Reading

    Chapter 22. Cytogenetic Analysis

    22.1 Introduction

    22.2 Milestones in Human Cytogenetics

    22.3 The Indications for Cytogenetic Analysis

    22.4 Tissue Samples and Cell Culture

    22.5 Chromosome Banding

    22.6 The Normal Human Karyotype

    22.7 Chromosome Abnormalities

    22.8 In situ Hybridization

    Acknowledgments

    Cross References

    References

    Further Reading

    Chapter 23. Diagnostic Molecular Genetics

    23.1 Introduction

    23.2 Indications for Molecular Genetic Testing

    23.3 Technical Approaches to Molecular Genetic Testing

    23.4 Molecular Genetic Diagnosis of Particular Diseases

    23.5 Mitochondrial DNA Disorders

    23.6 Other Targets of Molecular Genetic Screening

    23.7 Pharmacogenetic Testing

    23.8 Quality Assurance, Reimbursement, and Regulatory Issues

    23.9 Internet Resources for Molecular Genetic Testing

    23.10 Societal Impact of the New Genetic Technology

    References

    Chapter 24. Heterozygote Testing and Carrier Screening

    24.1 Introduction

    24.2 Carrier Screening in Clinical Practice

    24.3 Carrier Screening in Individuals of Defined Subpopulation Groups

    24.4 Therapeutic Implications for Heterozygotes

    24.5 Methods and Tissues Used in Carrier Identification

    24.6 Problems in Heterozygote Detection

    24.7 Sensitivity and Specificity

    24.8 Cost and Feasibility

    24.9 Age for Carrier Testing

    24.10 Conclusions

    Acknowledgments

    References

    Chapter 25. Prenatal Screening for Neural Tube Defects and Aneuploidy

    25.1 Introduction

    25.2 Neural Tube Defects

    25.3 Aneuploidy

    25.4 Summary

    References

    Chapter 26. Techniques for Prenatal Diagnosis

    26.1 Introduction

    26.2 Amniocentesis

    26.3 Chorionic Villus Sampling

    26.4 Fetal Blood Sampling

    26.5 Fetal Tissue Sampling

    26.6 Coelocentesis

    26.7 Embryoscopy

    26.8 Polar Body Biopsy

    26.9 Preimplantation Genetic Diagnosis

    26.10 Ultrasonography

    26.11 Fetal Cells and Fetal DNA in Maternal Blood

    26.12 Future Directions

    References

    Chapter 27. Neonatal Screening

    27.1 Introduction

    27.2 Historical Aspects

    27.3 Components of Screening Programs

    27.4 Potential Problems in Newborn Screening

    27.5 Disorders and Conditions Detected by Newborn Blood Screening

    27.6 Other Newborn Screening

    27.7 Issues and Concerns in Screening

    Cross References

    Glossary

    References

    Web Resources

    Further Reading

    Chapter 28. Therapies for Lysosomal Storage Diseases

    28.1 Introduction

    28.2 ERT for Lysosomal Storage Diseases

    28.3 Substrate Reduction Therapy

    28.4 Pharmacologic Chaperone Therapy

    28.5 Conclusions and Future Directions

    Acknowledgments

    Cross-References

    References

    Relevant Websites

    Chapter 29. Gene Therapy: From Theoretical Potential to Clinical Implementation

    29.1 Genes as Medicines—The Origins of Gene Therapy

    29.2 The Basic Science: Gene Transfer (Tables 29-1–29-3)

    29.3 Developing Cell-Type-Specific and Regulatable Gene Delivery Vectors

    29.4 The Clinical Science: Toward Gene Therapy of Human Disease

    29.5 CODA

    Cross References

    References

    Chapter 30. Ethical and Social Issues in Clinical Genetics

    30.1 Introduction

    30.2 The Historical Context

    30.3 Genetic Counseling, Testing and Screening

    30.4 Goals and Outcomes of Genetic Services

    30.5 Nondirectiveness in Genetic Counseling

    30.6 Diagnostic Genetic Testing

    30.7 Predictive Genetic Testing

    30.8 Confidentiality

    30.9 Genetic Testing in Childhood

    30.10 Population Genetic Screening

    30.11 Newborn Screening

    30.12 Antenatal Screening

    30.13 Carrier Screening

    30.14 Other Challenges in Genetic Counseling

    30.15 Research in Human Genetics

    30.16 Genetics, Geneticization and Society

    30.17 Reproductive Technologies and Cloning: “Reprogenetics”

    Acknowledgments

    Further Reading

    References

    Websites

    Chapter 31. Legal Issues in Genetic Medicine

    31.1 Introduction

    31.2 Genetic Malpractice and the Duty to Warn

    31.3 Genetic Counseling

    31.4 Abortion

    31.5 Adoption

    31.6 Surrogacy

    31.7 Frozen Embryos

    31.8 Newborn Screening

    31.9 Prenatal and Carrier Screening

    31.10 Genetic Discrimination

    31.11 Regulation of Genetic Diagnostic Tests

    31.12 Direct to Consumer Genetic Testing

    31.13 Regulation of Human Genetic Research

    31.14 Regulation of Research with Stem Cells Derived from Human Embryos

    31.15 Genes and Patents

    31.16 The Orphan Drug Act

    31.17 Conclusion

    Cross-references (Suggestions)

    References

    Further Reading

    Relevant Websites

    Applications to Clinical Problems

    Chapter 32. Genetics of Female Infertility in Humans

    32.1 The Hypothalamic–Pituitary–Gonadal Axis

    32.2 The Diagnosis of Hypogonadism

    32.3 Categories of Hypogonadism

    32.4 Eugonadal Infertility

    32.5 Specific Disorders in Each Diagnostic Category

    32.6 Hypogonadotropic Hypogonadism

    32.7 Hypergonadotropic Hypogonadism

    References

    Chapter 33. Genetics of Male Infertility

    33.1 Male Infertility—Introduction

    33.2 Chromosome Anomalies

    33.3 Gene defects Involved in Endocrine Forms of Infertility

    33.4 Monogenic Defects in Post-testicular and Primary Testicular Forms of Male Infertility

    33.5 Syndromic Monogenic Defects

    33.6 Conclusion

    References

    Chapter 34. Fetal Loss

    34.1 Background

    34.2 Definition of Terms

    34.3 Early Pregnancy Loss

    34.4 Late Pregnancy Loss

    34.5 Evaluation and Management of Recurrent Abortion

    34.6 Conclusions

    Cross References

    References

    Relevant Web sites

    Chapter 35. A Clinical Approach to the Dysmorphic Child

    35.1 Introduction

    35.2 Prenatal Versus Postnatal Onset of Developmental Problems

    35.3 Prenatal-Onset Problems in Development

    35.4 Postnatal-Onset Problems in Development

    35.5 Conclusion

    References

    Chapter 36. Clinical Teratology

    36.1 Introduction

    36.2 Evaluating the Patient and Her Exposure

    36.3 Recognized Teratogenic Exposures

    36.4 Paternal Exposures and Maternal Exposures before or Shortly after Conception

    36.5 Conclusion

    References

    Chapter 37. Neurodevelopmental Disabilities: Global Developmental Delay, Intellectual Disability, and Autism

    37.1 Intellectual Disability and Global Developmental Delay

    37.2 Global Developmental Delay

    37.3 Definition of a Diagnosis

    37.4 Genetic Mechanisms of ID

    37.5 Diagnostic Testing of Patients with ID of Unknown Cause

    37.6 Summary

    References

    Chapter 38. Abnormal Body Size and Proportion

    38.1 Introduction

    38.2 Pathologic Short Stature

    38.3 Pathologic Overgrowth

    Acknowledgments

    References

    Relevant Web Pages

    Chapter 39. Susceptibility and Response to Infection

    39.1 Introduction

    39.2 Heterozygous Advantage and Homozygous Disadvantage

    39.3 Genome-Wide Association Studies And Human Infection

    39.4 Cell Surface Proteins

    39.5 Intracellular Proteins

    39.6 Extracellular Proteins

    39.7 Conclusion

    References

    Chapter 40. Transplantation Genetics

    Abbreviations

    40.1 Introduction

    40.2 The Physiologic Function of MHC Molecules

    40.3 The Structure of Human Histocompatibility Molecules

    40.4 The Chromosomal Organization of the HLA Complex

    40.5 Minor Histocompatibility Systems

    40.6 Serologic Methods for HLA Typing

    40.7 Cellular Methods for HLA Typing

    40.8 Molecular Methods for HLA Typing

    40.9 Clinical Significance of HLA Molecular Typing

    40.10 Genetics of Xenotransplantation

    40.11 Stem Cells and Transplantation

    40.12 Conclusion

    Acknowledgments

    References

    List of Useful Websites

    Chapter 41. The Genetics of Disorders Affecting the Premature Newborn

    41.1 Introduction

    41.2 Respiratory Distress Syndrome

    41.3 Bronchopulmonary Dysplasia

    41.4 Patent Ductus Arteriosus

    41.5 Intraventricular Hemorrhage

    41.6 Retinopathy of Prematurity

    41.7 Necrotizing Enterocolitis

    References

    Chapter 42. Disorders of DNA Repair and Metabolism

    42.1 Mendelian Pattern of Inheritance

    42.2 Disorders of Nucleotide Excision Repair: Xeroderma Pigmentosum and Cockayne Syndrome

    42.3 Disorders of Base Excision Repair: MUTYH and Colon Cancer Risk

    42.4 Disorders of Mismatch Repair: Lynch Syndrome and Turcot Syndrome

    42.5 Disorders Associated With Double Strand Break Recognition and Repair: Ataxia-Telangiectasia and Related Conditions

    42.6 Crosslink Repair and Homologous Recombination Defects: Breast–Ovarian Cancer and Fanconi Anemia

    42.7 Disorders Associated with Recq Helicase Deficiency: Bloom, Werner, and Rothmund–Thomson Syndromes

    42.8 Gene–Environment Interactions: Gorlin–Goltz Syndrome

    References

    Applications to Specific Disorders

    Pathways

    Chapter 43. Autosomal Trisomies

    43.1 Introduction

    43.2 Genetic Counseling in the Trisomies

    43.3 Down Syndrome (Trisomy 21)

    43.4 Trisomy 18

    43.5 Trisomy 13

    References

    Chapter 44. Sex-Chromosome Abnormalities

    44.1 Introduction

    44.2 The Epidemiology of Sex-Chromosome Abnormalities

    44.3 Turner Syndrome

    44.4 Klinefelter Syndrome

    44.5 47,XXX Syndrome

    44.6 X Chromosome Mosaicism

    44.7 Sex Chromosome Tetrasomy and Pentasomy (Polysomy)

    44.8 47,XYY Karyotype

    44.9 Structural Abnormalities of the Y Chromosome

    44.10 Prenatal Diagnosis of Sex Chromosome Abnormalities

    References

    Further Reading

    Cross References

    Chapter 45. Deletions and Other Structural Abnormalities of the Autosomes

    45.1 Introduction

    45.2 Translocations

    45.3 Uniparental Disomy

    45.4 Deletion

    45.5 Duplication

    Cross References

    References

    Chromosomal Disorders

    Chapter 46. Congenital Heart Defects

    46.1 Introduction

    46.2 The Evaluation of the Patient with Congenital Heart Defect

    46.3 Specific Syndromes with Congenital Heart Defect

    46.4 Chromosomal Disorders

    46.5 Microdeletions/Microduplication Syndromes

    46.6 Single-Gene Disorders

    46.7 Holt–Oram syndrome

    46.8 CHARGE Syndrome

    46.9 Zellweger Syndrome

    46.10 Smith–Lemli–Opitz Syndrome

    46.11 Maternal Diabetes

    46.12 Maternal Cigarette Smoking

    46.13 Maternal Drug Ingestion

    46.14 Folic Acid Supplementation

    46.15 Empirical Risks for Sibs of Children with Isolated Heart Defects

    46.16 Empirical Risks for Offspring

    Appendix

    References

    Websites

    Chapter 47. Inherited Cardiomyopathies

    47.1 Introduction

    47.2 Hypertrophic Cardiomyopathy

    47.3 Dilated Cardiomyopathy

    47.4 Atypical Cardiomyopathies

    47.5 Conclusion

    Cross References

    References

    Further Reading

    Relevant Websites

    Chapter 48. Heritable and Idiopathic Forms of Pulmonary Arterial Hypertension

    48.1 Historical Perspectives and Introduction

    48.2 Nomenclature

    48.3 Incidence and Prevalence of HPAH and IPAH

    48.4 Phenotype and Natural History of HPAH and IPAH

    48.5 Inheritance and Genetics of PAH in Families

    48.6 Connecting BMPR2 to PAH

    48.7 Molecular and Cellular Pathogenesis

    48.8 Diagnosis

    48.9 Management

    48.10 Counseling

    Acknowledgments

    Abbreviations

    References

    Further Reading

    Relevant Websites

    Chapter 49. Hereditary Hemorrhagic Telangiectasia (Osler–Weber–Rendu Syndrome)

    49.1 Introduction

    49.2 Phenotype and Natural History

    49.3 Etiology

    49.4 Pathogenesis

    49.5 Diagnosis

    49.6 Management

    Acknowledgments

    References

    Chapter 50. Hereditary Disorders of the Lymphatic System and Varicose Veins

    50.1 Development of the Lymphatic System

    50.2 Disorders of the Lymphatic System

    50.3 Mendelian Disorders Affecting both the Lymphatic and Venous System

    50.4 Varicose Veins

    50.5 Genetic Counseling

    References

    Webpages

    Cross References

    Chapter 51. The Genetics of Cardiac Electrophysiology in Humans

    51.1 Introduction

    51.2 Specific Cardiac Dysrhythmias

    51.3 Primary Abnormalities in Cardiac Rhythm: Ventricular Tachydysrhythmias

    51.4 Primary Abnormalities in Cardiac Rhythm: Supraventricular Dysrhythmias

    51.5 Primary Conduction Abnormalities

    51.6 Familial Dysrhythmias Associated with Myocardial Disease

    51.7 Neurologic Disorders Associated with Dysrhythmias and Conduction Disease

    51.8 Congenital Heart Disease and Dysrhythmias or Conduction Disease

    51.9 Summary

    References

    Further Reading

    Chapter 52. Genetics of Blood Pressure Regulation

    52.1 Introduction

    52.2 Mendelian Forms of Hypertension

    52.3 Candidate Genes

    52.4 Genome-wide Association Studies

    Acknowledgment

    References

    Chapter 53. Preeclampsia

    53.1 Introduction

    53.2 Classification

    53.3 Pathologic and Molecular Basis

    53.4 Genetic Basis of Preeclampsia

    53.5 Animal Models

    References

    Relevant Web Pages

    Chapter 54. Common Genetic Determinants of Coagulation and Fibrinolysis

    54.1 Introduction

    54.2 Genetic Variants Influencing Components of the Coagulation Cascade

    54.3 Genetic Variants Influencing Natural Anticoagulants

    54.4 Genetic Variants Influencing Components of the Fibrinolytic Cascade

    54.5 Genetic Variants Influencing Platelet Function

    54.6 Genome-Wide Association Analysis for Thrombosis

    54.7 How do we Account for the Missing Heritability?

    54.8 Impact of Genetic Risk Factors on the Clinical Management of Thrombosis

    Cross References

    References

    Chapter 55. Genetics of Atherosclerotic Cardiovascular Disease

    Abbreviations

    55.1 Introduction

    55.2 Challenges to Genetic Studies of CHD

    55.3 Mouse Models of Atherosclerosis

    55.4 Candidate Gene Studies in Humans

    55.5 Genome Wide Association Studies

    55.6 GWAS Findings for CVD Risk Factors

    55.7 Genetic Risk Scores and Prediction Algorithms for Personalized Medicine

    55.8 Summary and Future Directions

    Cross References

    References

    Further Reading

    Chapter 56. Disorders of the Venous System

    56.1 Introduction

    56.2 The Venous System

    56.3 Disorders of the Venous System

    56.4 Conclusion

    Acknowledgments

    References

    Relevant Websites

    Chapter 57. Capillary Malformation/Arteriovenous Malformation

    57.1 Introduction

    57.2 Capillary Malformation

    57.3 Sturge–Weber Syndrome

    57.4 Capillary Malformation–arteriovenous Malformation

    57.5 Cerebral Cavernous Malformation

    Acknowledgments

    Cross References

    References

    Relevant Websites

    Cardiovascular Disorders

    Chapter 58. Cystic Fibrosis

    Abbreviation list

    58.1 Incidence of Cystic Fibrosis

    58.2 Clinical Features

    58.3 Genetics

    58.4 Diagnosis and Differential Diagnosis

    58.5 Management

    Acknowledgments

    References

    Chapter 59. Genetic Underpinnings of Asthma and Related Traits

    Glossary

    Nomenclature

    59.1 Introduction

    59.2 The Genetics of Asthma and Allergic Diseases

    59.3 Conclusion

    Acknowledgments

    Cross References

    References

    Relevant web pages

    Chapter 60. Hereditary Pulmonary Emphysema

    Abbreviations

    60.1 Introduction

    60.2 Diseases with Airflow Limitation: Definitions

    60.3 Phenotypic Evaluation in COPD

    60.4 Cigarette Smoking and COPD

    60.5 Severe AAT Deficiency

    60.6 Risk of COPD in Z Allele Heterozygotes

    60.7 COPD and COPD-Related Phenotypes in Other Genetic Syndromes

    60.8 Risk to Relatives for Non-AAT COPD

    60.9 Segregation Analysis

    60.10 Linkage Analysis

    60.11 Genetic Association Studies

    60.12 Animal Models of COPD

    60.13 Conclusions

    Acknowledgment

    References

    Relevant Websites

    Chapter 61. Interstitial and Restrictive Pulmonary Disorders

    61.1 Introduction

    61.2 Idiopathic Interstitial Pneumonia and Familial Interstitial Pneumonia

    61.3 Associated Polymorphisms in Other Common Forms of ILD

    61.4 Genetic Syndromes with ILD Manifestations

    References

    Respiratory Disorders

    Chapter 62. Congenital Anomalies of the Kidney and Urinary Tract

    Glossary

    62.1 Introduction

    62.2 Clinical Features

    62.3 Genetics

    62.4 Errors of Organogenesis

    62.5 Errors of Migration and Position

    62.6 Errors Resulting in Obstruction

    Cross References

    References

    Relevant Webpages

    Further Reading

    Chapter 63. Cystic Diseases of the Kidney

    63.1 Introduction

    63.2 Autosomal Dominant Polycystic Kidney Disease (MIM 173900)

    63.3 Autosomal Recessive Polycystic Kidney Disease (MIM 263200)

    63.4 Familial Nephronophthisis

    63.5 Medullary Cystic Kidney Disease

    63.6 Multicystic Dysplastic Kidney Disease (MKD)

    63.7 Genetic Syndromes with Cystic Renal Disease as a Major Component

    63.8 Mechanisms of Cystogenesis

    Cross References

    References

    Further Reading

    Relevant Web Pages

    Chapter 64. Nephrotic Disorders

    64.1 Introduction

    64.2 Glomerular Filtration Barrier

    64.3 Nephrin Gene (NPHS1) Mutations

    64.4 Podocin Gene (NPHS2) Mutations

    64.5 Wilms Tumor Suppressor Gene (WT1) Mutations

    64.6 Phospholipase Cε1 Gene (PLCE1) Mutations

    64.7 Laminin-β2 Gene (LAMB2) Mutations

    64.8 Transient Receptor Potential C6 Ion Channel Gene (TRPC6) Mutations

    64.9 CD2-Associated Protein Gene (CD2AP) Mutations

    64.10 Alpha-Actinin-4 Gene (ACTN4) Mutations

    64.11 NS Caused by Inverted Formin 2 Gene (INF2) Mutations

    64.12 Other Genetic Forms of NS

    64.13 Diagnosis of NS

    64.14 Management of NS Patients

    64.15 Conclusions

    References

    List of Relevant Websites

    Cross Reference

    Chapter 65. Renal Tubular Disorders

    65.1 Introduction

    65.2 Generalized Disorders of Tubular Function (Fanconi Syndrome)

    65.3 Disorders of Amino Acid Transport

    65.4 Renal Tubular Acidosis

    65.5 Disorders of Sugar Transport

    65.6 Hypophosphatemic Rickets

    65.7 Conclusion

    References

    Further Reading

    Cross References

    Chapter 66. Cancer of the Kidney and Urogenital Tract

    Abbreviations

    66.1 Tumors of the Kidney

    66.2 Bladder Neoplasms

    66.3 Carcinoma of the Prostate

    66.4 Testicular Neoplasms

    References

    Cross References

    Renal Disorders

    Chapter 67. Gastrointestinal Tract and Hepatobiliary Duct System

    Abbreviation

    67.1 Introduction

    67.2 Embryological Background

    67.3 Classification of Gastrointestinal Disorders

    References

    Relevant Web Pages

    Chapter 68. Inflammatory Bowel Disease

    Abbreviation

    68.1 Introduction and Disease Definition

    68.2 Phenotypic Heterogeneity

    68.3 Racial and Ethnic Differences

    68.4 Familial Aggregation

    68.5 Twin and Spouse Studies

    68.6 Inferences Regarding Mode of Inheritance

    68.7 Association of IBD With Rare Genetic Syndromes

    68.8 Associations with Other Diseases

    68.9 Gene and Environmental Interactions

    68.10 Gene Identification

    68.11 Candidate Gene Studies

    68.12 Clinical Application of Genetic Information

    References

    Further Reading

    Chapter 69. Bile Pigment Metabolism and Its Disorders

    69.1 Introduction

    69.2 Formation of Bilirubin

    69.3 Structure of Bilirubin

    69.4 Possible Physiologic Benefits of Biliverdin and Bilirubin

    69.5 Toxic Effects of Bilirubin

    69.6 Disposition of Bilirubin

    69.7 Bilirubin Measurement

    69.8 Bilirubin in Body Fluids

    69.9 Disorders of Bilirubin Metabolism

    Acknowledgments

    References

    Chapter 70. Cancer of the Colon and Gastrointestinal Tract

    70.1 Introduction

    70.2 The Genetics of Colorectal Cancer

    70.3 Familial Colorectal Cancer

    70.4 Other Familial Gastrointestinal Polyposis Syndromes

    70.5 Genetics of Gastric Cancer

    References

    Gastrointestinal Disorders

    Chapter 71. Hemoglobinopathies and Thalassemias

    71.1 Introduction

    71.2 Normal Human Hemoglobin

    71.3 Hemoglobin Biosynthesis

    71.4 Human Hemoglobin Variants

    71.5 Sickle-cell Anemia and Related Disorders

    71.6 Unstable Hemoglobin Variants

    71.7 Hemoglobin Variants with Altered Oxygen Affinity

    71.8 M Hemoglobin Variants

    71.9 Thalassemias

    References

    Chapter 72. Other Hereditary Red Blood Cell Disorders

    72.1 Hemolysis due to Hereditary Red Blood Cell Enzyme Disorders

    72.2 Purine and Pyrimidine Abnormalities Associated with Hemolysis

    72.3 Hemolysis due to Hereditary Red Blood Cell Membrane Disorders

    72.4 Megaloblastic Anemias

    72.5 Dyserythropoietic Anemias

    72.6 Sideroblastic Anemias

    72.7 Methemoglobinemia

    References

    Chapter 73. Hemophilias and Other Disorders of Hemostasis

    73.1 Overview of Hemostasis and Thrombosis

    73.2 The Coagulation Cascade

    73.3 Inherited Disorders Predisposing to Thrombosis

    References

    Chapter 74. Rhesus and Other Fetomaternal Incompatibilities

    74.1 Historical Background of Rh Alloimmunization

    74.2 Etiology of Alloimmunization

    74.3 Detection of Fetomaternal Hemorrhage

    74.4 Rh Blood Group System

    74.5 Alloimmune Thrombocytopenia

    74.6 Management of Alloimmunization

    References

    Further Reading

    Chapter 75. Leukemias, Lymphomas, and Other Related Disorders

    75.1 Introduction

    75.2 General Patterns of Chromosome Aberrations and Genomic Abnormalities in Leukemia and Lymphoma

    75.3 Significance of Detecting Acquired Chromosome and Gene Abnormalities in Leukemia and Lymphoma

    75.4 Application of Cytogenetic, Fish, and Microarray Techniques in Diagnosis of Leukemia and Lymphoma

    75.5 Myeloproliferative Neoplasm

    75.6 Myelodysplastic Syndromes

    75.7 Acute Myeloid Leukemia de Novo

    75.8 AML and MDS Associated with Prior Cytotoxic Treatment

    75.9 B-Cell Acute Lymphoblastic Leukemia

    75.10 Recurring Chromosome and Genomic Abnormalities in T-Cell ALL

    75.11 Leukemia in Children with Down Syndrome

    75.12 PreNatal Origins of Childhood Leukemia

    75.13 Non-Hodgkin Lymphomas

    75.14 Molecular Analysis of Recurrent Chromosome Abnormalities

    Cross References

    References

    Chapter 76. Immunologic Disorders: Autoimmunity: Genetics and Immunologic Mechanisms

    76.1 Introduction

    76.2 The Immune Response

    76.3 Autoimmune Pathology

    76.4 Autoreactive T Cells and the Failure of Tolerance

    76.5 Genetics of Autoimmune Diseases

    76.6 HLA Allelic Diversity and Population Genetics

    76.7 Genetic Susceptibility to Autoimmune Disease

    References

    Chapter 77. Systemic Lupus Erythematosus

    77.1 Introduction

    77.2 Historical Background, Definition, and Classification

    77.3 Pathogenic Autoantibodies and Immune Complexes

    77.4 The Genetics of Human SLE

    77.5 Gene Expression Patterns Associated with SLE

    77.6 Pregnancy Counseling of SLE Patients

    77.7 Concluding Remarks

    Cross Reference

    References

    Further Reading

    Chapter 78. Rheumatoid Disease and Other Inflammatory Arthropathies

    Glossary

    78.1 Introduction

    78.2 Rheumatoid Arthritis

    78.3 Seronegative Spondyloarthropathies

    78.4 Juvenile Idiopathic Arthritis

    References

    Chapter 79. Amyloidosis and Other Protein Deposition Diseases

    79.1 Introduction

    79.2 Hereditary Systemic Amyloidosis

    79.3 Hereditary Localized Amyloidosis

    79.4 Hereditary Non-Amyloid Protein Deposition Disease

    79.5 Conclusion

    References

    Chapter 80. Immunodeficiency Disorders

    80.1 Introduction

    80.2 Specific Inherited Immunodeficiency Disorders

    80.3 Primary B-cell Deficiencies (Humoral Immune Defects)

    80.4 Immunodeficiencies with Immune Dysregulation

    80.5 Immunodeficiency Syndromes

    80.6 Conclusion

    References

    Chapter 81. Inherited Complement Deficiencies

    81.1 Overview

    81.2 Introduction to the Complement System

    81.3 The Classical Pathway

    81.4 The Alternative Pathway

    81.5 The Lectin Activation Pathway

    81.6 The Membrane Attack Complex

    81.7 Regulation of Complement Activation

    81.8 Inherited Complement Deficiencies

    81.9 Management of Complement Deficiencies

    References

    Further Reading

    Hematologic Disorders

    Chapter 82. Disorders of Leukocyte Function

    82.1 Introduction

    82.2 Historical Background

    82.3 Phagocyte Development, Kinetics, and Functions

    82.4 Granulocyte Function Disorders

    82.5 Monocytes/Macrophages Function Disorders

    Cross References

    References

    Chapter 83. Genetic Disorders of the Pituitary Gland

    83.1 Introduction

    83.2 Anterior Pituitary

    83.3 Posterior Pituitary: Genetic Disorders of AVP Deficiency

    83.4 Genetic Testing

    References

    Chapter 84. Thyroid Disorders

    84.1 Introduction

    84.2 Congenital Hypothyroidism

    84.3 Genetic Hyperthyroidism

    84.4 Thyroid Disease Associated with Chromosomal Abnormalities and Contiguous Gene Deletion Syndromes

    84.5 Genetic Basis of Autoimmune Thyroid Disease

    84.6 Genetic Basis of Thyroid Carcinoma

    References

    Chapter 85. Parathyroid Disorders

    85.1 Calcium Homeostasis

    85.2 Primary Hyperparathyroidism

    85.3 Familial Hypocalciuric Hypercalcemia

    85.4 Neonatal Severe Hyperparathyroidism

    85.5 CASR Mutations in Familial Hypocalciuric Hypercalcemia and Neonatal Severe Hyperparathyroidism

    85.6 Mucolipidosis and Neonatal Hyperparathyroidism

    85.7 Multiple Endocrine Neoplasia

    85.8 Multiple Endocrine Neoplasia Type 1

    85.9 Multiple Endocrine Neoplasia Type 2

    85.10 Multiple Endocrine Neoplasia Type 4

    85.11 Hyperparathyroidism-Jaw Tumor Syndrome

    85.12 Other Hereditary Hyperparathyroidism

    85.13 Diagnosis and Differential Diagnosis of Hypercalcemia

    85.14 Jansen Metaphyseal Chondrodysplasia (Pseudohyperparathyroidism)

    85.15 Primary Hypoparathyroidism

    85.16 Familial Isolated Hypoparathyroidism

    85.17 Hypoparathyroidism with Multiple Malformations

    85.18 Hypoparathyroidism Due to Metabolic Disease

    85.19 Autoimmune Hypoparathyroidism: Acquired and Inherited Disorders

    85.20 Pseudohypoparathyroidism

    85.21 Other Phenotypes Associated with GNAS Mutations

    85.22 The Parathyroid Hormone Receptor and Skeletal Dysplasias

    85.23 NHERF1 Mutations and Renal Responsiveness to Parathyroid Hormone

    85.24 Hypomagnesemia

    85.25 Management of Hypoparathyroidism

    Cross References

    References

    Websites

    Chapter 86. Diabetes Mellitus

    86.1 Introduction

    86.2 Difficulties in Genetic Studies of Diabetes

    86.3 Diabetes in Families and Twins

    86.4 Genetic Heterogeneity in Diabetes

    86.5 Type 2 Diabetes Mellitus

    86.6 Final Considerations and Speculations

    Cross References

    References

    Further Reading

    Relevant Web Pages

    Chapter 87. Genetic Disorders of the Adrenal Gland

    87.1 Clinical Aspects: Normal and Abnormal Adrenal Function

    87.2 Steroid 21-Hydroxylase Deficiency

    87.3 Steroid 11β-Hydroxylase Deficiency

    87.4 3β-Hydroxysteroid Dehydrogenase Deficiency

    87.5 Steroid 17α-Hydroxylase/17,20-Lyase Deficiency

    87.6 Congenital Lipoid Adrenal Hyperplasia

    87.7 Treatment

    87.8 Congenital Adrenal Hyperplasia: Prenatal Diagnosis and Treatment

    Acknowledgment

    References

    Further Reading

    Chapter 88. Disorders of the Gonads, Genital Tract, and Genitalia

    88.1 Introduction

    88.2 46,XX Disorders of Sexual Development

    References

    Further reading

    Chapter 89. Cancer of the Breast and Female Reproductive Tract

    89.1 Historical Background: Mapping Breast Cancer Genes

    89.2 Discovery of BRCA1

    89.3 Discovery of BRCA2

    89.4 Pathology of Familial Breast Cancers

    89.5 BRCA1 and BRCA2 Mutation Analysis

    89.6 Rare Familial Syndromes Associated with Increased Risk for Breast or Ovarian Cancer

    89.7 Low-Penetrance Breast Cancer Genes

    89.8 Association Studies and Genomics of Breast Cancer

    89.9 Hereditary Nonpolyposis Colorectal Cancer Syndrome (or Lynch Syndrome)

    89.10 Endometrial Cancer

    89.11 Familial Ovarian Cancer

    89.12 Cervical Cancer

    89.13 Implications of Familial Breast and Ovarian Cancers for Clinical Practice

    89.14 Impact of Definitive Genetic Diagnosis on Clinical Practice

    References

    Endocrinologic Disorders

    Chapter 90. Disorders of the Body Mass

    90.1 Overview

    90.2 Genetic Architecture of Obesity

    90.3 Mendelian Disorders Associated with Increased BMI in Humans

    References

    Chapter 91. Genetic Lipodystrophies

    91.1 Introduction

    91.2 Mechanisms of Insulin Resistance and its Complications in Lipodystrophies

    91.3 Genetic Lipodystrophies

    91.4 Long-Term Complications

    91.5 Treatment Options

    References

    Chapter 92. Amino Acid Metabolism

    92.1 Disorders of Phenylalanine Metabolism

    92.2 Disorders of Tyrosine Metabolism

    92.3 Disorders of Glycine Metabolism

    92.4 Disorders of Sulfur-Containing Amino Acids

    92.5 Disorders of the BCAAs

    92.6 Disorders of Proline and Hydroxyproline

    92.7 Disorders of the Urea Cycle and Ornithine

    92.8 Disorders of Serine Metabolism

    92.9 Disorders of Amino Acids without Known Clinical Consequences

    References

    Further Reading

    Chapter 93. Disorders of Carbohydrate Metabolism

    93.1 Introduction

    93.2 Disaccharidase Deficiencies

    93.3 Glucose–Galactose Malabsorption

    93.4 Disorders of Galactose Metabolism

    93.5 Disorders of Fructose Metabolism

    93.6 Disorders of Pentose Metabolism

    93.7 Glycogen Storage Diseases

    93.8 GSDs Primarily Involving the Liver

    93.9 Other Liver Glycogenoses

    93.10 GSD Primarily Involving Muscle

    93.11 GSD Primarily with Cardiac Involvement

    93.12 Gluconeogenic Disorders Associated with Lactic Acidosis

    Acknowledgments

    Cross References

    References

    Chapter 94. Congenital Disorders of Protein Glycosylation

    94.1 Normal Protein Glycosylation

    94.2 Congenital Disorders of Protein N-Glycosylation

    94.3 Congenital Disorders of Protein O-Glycosylation

    94.4 Congenital Disorders of Protein N- and O-Glycosylation

    94.5 Perspectives

    Cross References

    References

    Further Reading

    Chapter 95. Purine and Pyrimidine Metabolism

    Glossary

    95.1 Introduction

    95.2 Purine Metabolism

    95.3 Pyrimidine Metabolism

    Acknowledgments

    Cross Reference

    References

    Further Reading

    Chapter 96. Lipoprotein and Lipid Metabolism

    Abbreviations

    96.1 Introduction

    96.2 Plasma Lipids, Lipoproteins And Apolipoproteins

    96.3 Lipoprotein Metabolism

    96.4 Monogenic Disorders of Lipoprotein Metabolism

    96.5 Disorders with Primarily Elevated LDL Cholesterol

    96.6 Disorders with Primarily Depressed LDL Cholesterol

    96.7 Disorders with Primarily Elevated HDL Cholesterol

    96.8 Disorders with Primarily Depressed HDL Cholesterol

    96.9 Disorders with Primarily Elevated Triglycerides

    96.10 Disorders with Multiple Lipoprotein Disturbances

    96.11 Other Dyslipoproteinemias

    96.12 General Priniciples in the Management of Dyslipidemia

    96.13 Conclusion

    References

    Further reading

    Relevant Web Pages

    Chapter 97. Organic Acidemias and Disorders of Fatty Acid Oxidation

    97.1 Organic Acidemias

    97.2 Other Organic Acidemias

    97.3 Disorders of Fatty Acid Oxidation: introduction

    Cross References

    References

    Further Reading

    Relevant Web Pages

    Chapter 98. Vitamin D Metabolism or Action

    98.1 History

    98.2 Normal Physiology of Calciferols

    98.3 5,6-cis-trans-isomerization

    98.4 General Features of Calciferol Deficiency

    98.5 Hereditary Vitamin D Dependency Type 1 (VDDR-1)-1-α-Hydroxylase Deficiency

    98.6 Hereditary Vitamin D-Dependent Rickets Type 2 (VDDR-2)

    98.7 States Resembling Hereditary Generalized Resistance to 1,25(OH)2D

    98.8 Other Hereditary Defects in Calciferol Metabolism or Action

    References

    Further Reading

    Chapter 99. Inherited Porphyrias

    99.1 Introduction

    99.2 The Heme Biosynthetic Pathway

    99.3 Regulation of Heme Biosynthesis

    99.4 Classification and Diagnosis of the Porphyrias

    Acknowledgments

    Chapters to Cross-Reference

    Further Reading

    Relevant Web Pages

    Chapter 100. Inherited Disorders of Human Copper Metabolism

    100.1 Introduction

    100.2 Menkes Disease

    100.3 Wilson Disease

    Acknowledgments

    References

    Chapter 101. Iron Metabolism and Related Disorders

    101.1 Introduction

    101.2 Iron Balance and the Iron Cycle

    101.3 Syndromes of Iron Overload

    101.4 Other Disorders Resulting in Derangements of Iron Handling

    References

    Chapter 102. Mucopolysaccharidoses

    102.1 General Aspects

    102.2 Mucopolysaccharidosis I (IH Hurler, IS Scheie and IH/S Hurler–Scheie Disease)

    102.3 Mucopolysaccharidosis II (Hunter Syndrome)

    102.4 Mucopolysaccharidosis IIIA (Sanfilippo Syndrome, MPS IIIA)

    102.5 Mucopolysaccharidosis IIIB (Sanfilippo Syndrome, MPS IIIB)

    102.6 Mucopolysaccharidosis IIIC (Sanfilippo Syndrome, MPS IIIC)

    102.7 Mucopolysaccharidosis IIID (Sanfilippo Syndrome, MPS IIID)

    102.8 Mucopolysaccharidosis IVA and IVB (Morquio Syndrome, MPS IVA, MPS IVB)

    102.9 Mucopolysaccharidosis V (Scheie Syndrome, MPS V)

    102.10 Mucopolysaccharidosis VI (Maroteaux–Lamy Syndrome, MPS VI)

    102.11 Mucopolysaccharidosis VII (Sly Syndrome, MPS VII)

    102.12 Mucopolysaccharidosis VIII

    102.13 Mucopolysaccharidosis IX (Natowicz Syndrome, MPS IX)

    Appendix A Supplementary Data

    References

    Relavent Web Sites

    Further Reading

    Chapter 103. Oligosaccharidoses: Disorders Allied to the Oligosaccharidoses

    103.1 Oligosaccharidoses

    103.2 Disorders Allied to Oligosaccharidoses

    Acknowledgments

    References

    Relevant Webpages

    Chapter 104. Sphingolipid Disorders and the Neuronal Ceroid Lipofuscinoses or Batten Disease (Wolman Disease, Cholesteryl Ester Storage Disease, and Cerebrotendinous Xanthomatosis)

    Glossary

    104.1 Introduction

    104.2 GM1-Gangliosidosis (β-Galactosidosis)

    104.3 GM2-Gangliosidosis

    104.4 Loss-of-Function Mutation of GM3-Synthase

    104.5 Niemann–Pick Disease

    104.6 Niemann–Pick Disease, Types A and B

    104.7 Niemann–Pick Disease, Types C and D

    104.8 Farber’s Disease

    104.9 Acid Lipase Deficiency (Wolman Disease and Cholesteryl Ester Storage Disease)

    104.10 Gaucher Disease

    104.11 Galactosylceramide Lipidosis, Globoid Cell Leukodystrophy, or Krabbe Disease

    104.12 Metachromatic Leukodystrophy

    104.13 Fabry Disease

    104.14 Neuronal Ceroid Lipofuscinosis or Batten Disease

    104.15 Kufs Disease or Adult NCL

    104.16 Congenital NCL/CNCL-CLN10/Cathepsin D or CTSD Deficiency

    Acknowledgment

    References

    Chapter 105. Peroxisomal Disorders

    Abbreviations

    105.1 Introduction

    105.2 Physiological Role of Peroxisomes

    105.3 Additional Peroxisomal Functions

    105.4 Biogenesis of Peroxisomes

    105.5 Single Peroxisomal Enzyme Deficiencies

    105.6 Rare Peroxisomal Disorders

    Reference

    Metabolic Disorders

    Chapter 106. The Genetics of Personality

    106.1 The Nature of Personality

    106.2 Twin and Adoption Studies

    106.3 The Search for Genes that Influence Personality

    106.4 Strategies to Increase the Sensitivity of Genetic Studies of Personality

    106.5 Gene–Environment Interplay and the Development of Personality

    106.6 Conclusion

    Cross References

    References

    Further Reading

    Chapter 107. Fragile X Syndrome and X-linked Intellectual Disability

    107.1 Overview

    107.2 Fragile X Syndrome

    107.3 Other Forms of XLID

    107.4 Conclusion

    Cross References

    References

    Further Reading

    Chapter 108. Dyslexia and Related Communication Disorders

    Abbreviations

    108.1 Introduction

    108.2 Definition

    108.3 Primary Cognitive Deficit of Specific Reading Disability

    108.4 Inheritance

    108.5 Comorbidity

    108.6 Recurrence Risks

    108.7 Diagnosis and Differential Diagnosis

    108.8 Treatment

    References

    Chapter 109. Attention-Deficit/Hyperactivity Disorder

    109.1 Behavioral Genetics

    109.2 Molecular Genetics

    109.3 Conclusions

    Cross References

    References

    Relevant Web Pages

    Chapter 110. Autism Spectrum Disorders

    110.1 Background

    110.2 Diagnosis and Clinical Work Up

    110.3 Medical Comorbidities

    110.4 Etiology: Genes and the Environment

    110.5 Pathophysiology

    110.6 Syndromic Forms of ASD and Structural Chromosomal Variation

    110.7 Linkage and Endophenotypes

    110.8 Genome Wide Association Studies

    110.9 Candidate Genes

    110.10 Variable Expressivity and Variable Penetrance—Psychiatric Comorbidity and Disease Boundary Confusion

    110.11 Conclusion

    References

    Chapter 111. Genetics of Alzheimer Disease

    111.1 Background and History

    111.2 Genetics of EOAD

    111.3 Genetics of LOAD

    References

    Further Reading

    Chapter 112. Schizophrenia and Affective Disorders

    Glossary

    112.1 Introduction

    112.2 History and Definitions of the Disorders

    112.3 Biology of the Disorders

    112.4 Evidence Supporting a Genetic Component

    112.5 Role of Genetics in Clinical Practice

    112.6 Summary

    Cross References

    References

    Further Reading and other sections refer to PPMG article template doc

    Chapter 113. Addictive Disorders

    113.1 Introduction

    113.2 Genetic Aspects of Addiction

    113.3 Gene Identification

    113.4 Treatment of Addictions

    113.5 Conclusion

    References

    Mental and Behavioral Disorders

    Chapter 114. Neural Tube Defects

    114.1 Embryology

    114.2 Definition

    114.3 Prevalence

    114.4 Risk Factors

    114.5 Diagnosis, Treatment, and Outcome

    114.6 Prevention

    114.7 Genetic Counseling

    Acknowledgments

    References

    Further Reading

    Chapter 115. Genetic Disorders of Cerebral Cortical Development

    115.1 Introduction

    115.2 Malformations Due to Abnormal Neuronal and Glial Proliferation or Apoptosis

    115.3 Malformations Due to Abnormal Neuronal Migration

    115.4 Malformations Due to Abnormal Cortical Organization

    115.5 Malformations of Cortical Development, Not Otherwise Classified

    115.6 Conclusions

    Acknowledgments

    Cross References

    References

    Further Reading

    List of Relevant Web Pages

    Chapter 116. Genetic Aspects of Human Epilepsy

    Abbreviations

    116.1 Introduction

    116.2 Epilepsy: Definition

    116.3 Epilepsy: Neurophysiological Basis

    116.4 EEG in Epilepsy

    116.5 Seizure Types, Epilepsy Syndromes

    116.6 Genetic Studies in Human Epilepsy

    116.7 Mechanistic Diversity in Genetic Epilepsy

    116.8 Selected Genetic Epilepsy Syndromes

    116.9 Clinical and Laboratory Evaluation

    116.10 Genetic Counseling Issues in Epilepsy

    116.11 Pharmacogenomics Issues in Epilepsy

    116.12 Epilepsy and Pregnancy

    116.14 Summary

    Acknowledgments

    Cross References

    References

    Relevant Webpages

    Chapter 117. Basal Ganglia Disorders

    117.1 Introduction

    117.2 Diseases with Parkinsonism

    117.3 Parkinson Disease

    117.4 Parkinson Plus Syndromes

    117.5 General Clinical Features of the Dystonias

    117.6 Management and Treatment

    117.7 Choreic Disorders

    117.9 Clinical Features

    Cross References

    References

    Further Reading

    Chapter 118. The Hereditary Ataxias

    118.1 Recessive Ataxias Caused by Catalytic Deficiencies

    118.2 Intermittent Ataxias

    118.3 Progressive Ataxias from Metabolic Insufficiency

    118.4 Progressive Ataxias that are not Because of Metabolic Defects

    118.5 Progressive Ataxias Associated with Defective DNA Repair Mechanisms

    118.6 Other Recessive Progressive Ataxias

    118.7 The Autosomal-Dominant Hereditary Ataxias

    118.8 Episodic Ataxias

    118.9 X-linked ataxias

    118.10 Mitochondrial Ataxias

    118.11 Conclusions

    References

    List of Relevant Web Pages

    Chapter 119. Hereditary Spastic Paraplegia

    119.1 Introduction

    119.2 Maternal (Mitochondrial Genome) Inheritance

    119.3 Association of HSP Gene Mutations with Syndromes Other than Spastic Paraparesis

    119.4 Autosomal Dominant HSP

    119.5 Autosomal Recessive HSP Genes

    119.6 X-Linked HSP Genes

    119.7 Emerging Concepts of HSP Pathogenesis

    119.8 Animal Models of HSP

    119.9 Conclusions

    Cross-References

    Acknowledgments

    References

    Chapter 120. Autonomic and Sensory Disorders

    120.1 Introduction

    120.2 Familial Dysautonomia

    120.3 Congenital Sensory Neuropathy with Anhidrosis (HSAN Type IV)

    References

    Chapter 121. The Phakomatoses

    121.1 Introduction

    121.2 The Neurofibromatoses

    Acknowledgments

    References

    Chapter 122. Multiple Sclerosis and Other Demyelinating Disorders

    122.1 Introduction

    122.2 Pediatric MS

    122.3 Practical Applications of Genetic Studies

    122.4 Krabbe Disease (Globoid Cell Leukodystrophy)

    122.5 Metachromatic Leukodystrophy

    122.6 X-Linked Adrenoleukodystrophy

    References

    Chapter 123. Genetics of Stroke

    123.1 Introduction

    123.2 Stroke Phenotypes

    123.3 Heritability: Twin and Family Studies

    123.4 Single-Gene Disorders Causing Stroke

    123.5 CVT – Cerebral Venous Thrombosis (FVL, prothrombin)

    123.6 Genome-Wide Association Studies and Genomics

    123.7 Summary

    Acknowledgment

    References

    Chapter 124. Primary Tumors of the Nervous System

    Abbreviations

    124.1 Introduction

    124.2 Epidemiology

    124.3 Classification

    124.4 Inherited Tumor Syndromes Predisposing to Central Nervous System Tumors

    124.5 Relative Risk of Cancer in First-Degree Relatives

    124.6 Glial Tumors

    124.7 Primitive Neuroectodermal Tumor and Medulloblastoma

    124.8 Schwannoma (Neurilemmoma, Neurinoma)

    124.9 Meningioma

    Cross References

    References

    Relevant Webpages

    Further Reading

    Neurologic Disorders

    Chapter 125. Muscular Dystrophies

    Glossary

    125.1 Introduction

    125.2 Dystrophinopathies

    125.3 Facioscapulohumeral Muscular Dystrophy

    125.4 Emery–Dreifuss Muscular Dystrophies and Other Contractural Phenotypes

    125.5 Limb-Girdle Muscular Dystrophies

    125.6 Myofibrillar Myopathies and Other Distal Phenotypes

    125.7 Congenital Muscular Dystrophies

    125.8 Conclusions

    References

    List of relevant Relevant Web pages

    Further Reading

    Chapter 126. Hereditary Motor and Sensory Neuropathies

    126.1 Introduction

    126.2 Hereditary Motor and Sensory Neuropathies

    126.3 Diseases Phenotypes

    126.4 Distal Symmetric Polyneuropathy—Evidence-Based Medical Guidelines

    126.5 Modes of Inheritance

    126.6 Genetics

    126.7 Charcot–Marie–Tooth “disease genes” Reveal a Cellular and Myelin Development/Maintenance Network

    126.8 Genetic Counseling

    126.9 Summary

    Further Information

    References

    Chapter 127. Congenital (Structural) Myopathies

    127.1 Introduction

    127.2 Diagnosis

    127.3 Management

    127.4 Genetic Counseling

    127.5 Nemaline (Rod) Myopathy

    127.6 Myotubular (Centronuclear) Myopathies

    127.6.7 Pathogenetic Considerations

    127.7 The “Core Myopathies”: CCD and MmD

    127.8 Congenital Fiber Type Disproportion

    127.9 Myosin Storage (Hyaline Body) Myopathy

    127.10 Myofibrillar Myopathies

    Acknowledgments

    References

    Chapter 128. Spinal Muscular Atrophies

    128.1 Introduction: Definition

    128.2 Proximal Spinal Muscular Atrophy

    128.3 Nonproximal Spinal Muscular Atrophy

    128.4 Management

    References

    Chapter 129. Hereditary Muscle Channelopathies

    129.1 Introduction

    129.2 Electrophysiology of Clinical Weakness and Paralysis

    129.3 Hereditary Channelopathies Affecting the End Plate

    129.4 Hereditary Channelopathies Affecting the Plasmalemma

    129.5 Hereditary Channelopathies of Excitation–Contraction Coupling

    129.6 Critical Points in Functional and Genetic Studies

    Acknowledgment

    References

    Relevant Web Pages

    Chapter 130. Myotonic Dystrophies

    130.1 Introduction

    130.2 Clinical Features

    130.4 Genetics

    130.5 Molecular and Cell Biology

    130.6 Genetic Counseling and Risk Estimation

    130.7 Management

    Cross References

    References

    Further Reading

    Relevant Web Pages

    Chapter 131. Hereditary and Autoimmune Myasthenias

    131.1 Introduction

    131.2 Normal Neuromuscular Transmission

    131.3 Diagnostic Methods

    131.4 Acetylcholine Receptor

    131.5 Congenital Myasthenic Syndromes

    131.6 Acquired Autoimmune Myasthenia Gravis

    131.7 Immunogenetic Associations

    131.8 Management

    131.9 Lambert–Eaton Myasthenic Syndrome

    References

    Further Reading

    Chapter 132. Motor Neuron Disease

    132.1 Introduction

    132.2 History

    132.3 Epidemiology

    132.4 Clinical Features

    132.5 Clinical Variants of Amyotrophic Lateral Sclerosis

    132.6 Pathology

    132.7 Genetics of Familial Amyotrophic Lateral Sclerosis

    132.8 Genetics of Sporadic Amyotrophic Lateral Sclerosis

    132.9 Conclusion

    References

    Neuromuscular Disorders

    Chapter 133. Color Vision Defects

    133.1 Introduction

    133.2 Photoreceptors

    133.3 Molecular Biology of the Photopigments

    133.4 Phototransduction

    133.5 Genes Encoding the Photopigments

    133.6 Color Vision Tests

    133.7 The Molecular Basis of Variation in Normal Color Vision

    133.8 The Molecular Basis of Color Vision Defects

    133.9 The Genetics of Red–green Color Vision in Women

    133.10 Blue–Yellow (Tritan) Color Vision Defects

    133.11 The Achromatopsias

    Acknowledgment

    References

    Websites

    Further Reading

    Chapter 134. Optic Atrophy

    Glossary

    134.1 Introduction

    134.2 “Primary” Optic Atrophies

    134.3 Complex Optic Atrophies

    References

    Chapter 135. Glaucoma

    135.1 Introduction

    135.2 Clinical Features of Heritable Forms of Glaucoma

    135.3 Identification of Glaucoma Genes Using Linkage Analysis

    135.4 Genes Causing Glaucoma in Animal Models

    135.5 Identification of Glaucoma Genes Using Genomic Approaches

    135.6 Conclusion

    Cross References

    References

    Further Reading

    Chapter 136. Defects of the Cornea

    Glossary

    136.1 Introduction

    136.2 Dystrophies

    136.3 Defects Associated with Systemic Disease

    136.4 Other Inherited Corneal Abnormalities

    136.5 Conclusion

    References

    Chapter 137. Congenital Cataracts and Genetic Anomalies of the Lens

    Glossary

    137.1 Introduction

    137.2 Noncataractous Anomalies

    137.3 Cataracts

    137.4 Therapy

    Acknowledgments

    References

    List of Relevant Web Pages

    Chapter 138. Hereditary Retinal and Choroidal Dystrophies

    138.1 Introduction

    138.2 Inheritance Patterns and Molecular Genetics

    138.3 Pigmentary Retinopathies/Retinitis Pigmentosa

    138.4 Leber’s Congenital Amaurosis

    138.5 The Primary Cone Degenerations

    Cross References

    References

    Chapter 139. Strabismus

    139.1 Introduction

    139.2 Incidence and Pathophysiology

    139.3 Clinical Background

    139.4 Isolated Strabismus

    139.5 Single Gene Defect Disorders

    139.6 Strabismus Associated with Other Ocular Disease

    139.7 Strabismus Associated with Multisystem Disease

    139.8 Summary

    References

    Chapter 140. Retinoblastoma and the RB1 Cancer Syndrome

    140.1 Introduction

    140.2 Incidence and Prevalence

    140.3 Theories of Tumorigenesis and RB1

    140.4 The Natural History of Retinoblastoma Tumorigenesis

    140.5 The RB1 Cancer Syndrome

    140.6 Non-heritable (Somatic or Postzygotic) Retinoblastoma

    140.7 Features of Retinoblastoma Common to Heritable and Non-heritable Cases

    140.8 Clinical Genetics and Genetic Counseling

    140.9 Approaches to Prenatal Assessment and Diagnosis

    140.10 Conclusions

    Cross References

    References

    Further Reading

    Chapter 141. Anophthalmia, Microphthalmia, and Uveal Coloboma

    Glossary

    141.1 Introduction

    141.2 Anophthalmia, Microphthalmia, and Uveal Coloboma

    141.3 Genes and Syndromes Associated with Anophthalmia, Microphthalmia, and/or Uveal Coloboma

    141.4 A Clinical Approach to the Patient with AMC

    141.5 Persistence of the Fetal Vasculature/Persistent Hyperplastic Primary Vitreous

    References

    Further Reading

    Relevant Websites

    Ophthalmologic Disorders

    Chapter 142. Hereditary Hearing Impairment

    Glossary

    Abbreviations

    142.1 Introduction

    142.2 Anatomy and Physiology

    142.3 Prevalence and Classification of HL

    142.4 Acquired Hearing Impairment

    142.5 Teratogenic Hearing Impairment

    142.6 Nonsyndromic Hereditary Hearing Impairment

    142.7 Syndromic Hereditary Hearing Impairment

    142.8 Inborn Metabolic Errors

    142.9 Diagnosis and Differential Diagnosis

    References

    Further reading

    Deafness

    Chapter 143. Clefting, Dental, and Craniofacial Syndromes

    143.1 Introduction

    143.2 Development

    143.3 Epidemiology

    143.4 Genetics

    143.5 Clinical Exam and Physical Findings

    143.6 Conclusion

    References

    Chapter 144. Craniosynostosis

    Glossary

    144.1 Introduction

    144.2 Skull and Sutural Development

    144.3 Genetic Epidemiology of Craniosynostosis

    144.4 Craniosynostosis Syndromes

    144.5 Genes Responsible for Craniosynostosis

    144.6 Other Syndromes with Craniosynostosis and their Genes

    144.7 Non-syndromic Craniosynostoses and their Genes

    144.8 Evaluation of Craniosynostosis

    References

    Craniofacial Disorders

    Chapter 145. Abnormalities of Pigmentation

    145.1 Introduction

    145.2 The Pigmentary System

    145.3 Genetics and Disorders of Human Pigmentation

    145.4 Disorders of Melanosome Biogenesis/Transport—Hermansky–Pudlak Syndrome, Chédiak–Higashi Syndrome, and Griscelli Syndrome

    145.5 Disorders of Melanocyte Survival—Vitiligo

    Acknowledgment

    References

    Chapter 146. Ichthyosiform Dermatoses

    146.1 Introduction

    146.2 Approach to Diagnosis of Ichthyosis

    146.3 The Morphology of Normal Skin

    146.4 Ichthyosis Vulgaris

    146.5 X-linked Ichthyosis

    146.6 Autosomal Recessive Congenital Ichthyosis

    146.7 Epidermolytic Hyperkeratosis

    146.8 Ichthyosis of the Newborn

    146.9 Hyperkeratosis of the Palms and Soles

    146.10 Rare Ichthyoses

    146.11 Phenotype by Function: Advances in Understanding

    A List of Websites of Use to the Reader in Regard of the Topic

    Cross Reference

    References

    Further Reading

    Chapter 147. Epidermolysis Bullosa

    Glossary

    147.1 Introduction

    147.2 Molecular Basis of Epidermal and Dermo-epidermal Adhesion

    147.3 Classification

    147.4 Clinical Features

    147.5 Differential Diagnosis

    147.6 Molecular Genetics of Epidermolysis Bullosa

    147.7 Treatment and Therapeutics

    147.8 Revertant Mosaicism

    147.9 Animal Models

    147.10 The Role of Patient Advocacy Organizations

    Cross References

    References

    Further Reading

    List of Websites Relavant to EB

    Chapter 148. Ectodermal Dysplasias

    Glossary

    148.1 Introduction

    148.2 Hypohidrotic Ectodermal Dysplasia

    148.3 Odonto–Onycho–Dermal Dysplasia (OODD) Syndrome (MIM 257980)

    148.4 P63-Related Ectodermal Dysplasia Syndromes

    148.5 Ectrodactyly, Ectodermal Dysplasia, and Cleft Lip/Palate Syndrome (MIM 604292)

    148.6 Ankyloblepharon, Ectodermal Defects, Cleft Lip/Palate (MIM 106260)

    148.7 Rapp–Hodgkin Syndrome (MIM 129400)

    148.8 Adult (Acro–Dermato–Ungual–Lacrimal–Tooth) Syndrome (MIM 103285)

    148.9 Limb–Mammary Syndrome (MIM 603543)

    148.10 Split Hand/Split Foot Malformation (SHFM4) (MIM 605289)

    148.11 Hidrotic Ectodermal Dysplasia (Clouston Syndrome) (MIM 129500)

    148.12 Tooth and Nail Syndrome (Witkop Syndrome)(MIM 189500)

    148.13 IKBKG Gene-Related Disorders

    Cross References

    References

    Relevant Web Pages

    Further Reading

    Chapter 149. Skin Cancer

    149.1 Introduction

    149.2 Basal Cell Carcinoma

    149.3 Nevoid Basal Cell Carcinoma Syndrome (Gorlin–Goltz Syndrome)

    149.4 Bazex–Dupre–Christol Syndrome

    149.5 Squamous Cell Carcinoma

    149.6 Xeroderma Pigmentosum

    149.7 Multiple Self-healing Epitheliomas of Ferguson Smith

    149.8 Epidermodysplasia Verruciformis

    149.9 Recessive Dystrophic Epidermolysis Bullosa (of the Hallopeau–Siemens Type)

    149.10 Porokeratoses

    149.11 Muir–Torre Syndrome

    149.12 Melanoma

    Further Reading

    Cross References

    References

    Chapter 150. Psoriasis

    Glossary

    150.1 Introduction

    150.2 Clinical Features and Subtypes

    150.3 Prevalence, Age at Onset and Sex Ratio

    150.4 Genetic Epidemiology

    150.5 Environmental Factors

    150.6 Comorbidities

    150.7 Histopathology and Lesional Evolution

    150.8 Immunopathogenesis

    150.9 Psoriasis Susceptibility Loci and their Roles in Disease Pathogenesis

    150.10 Management

    150.11 Conclusion

    Cross References

    References

    Further Reading

    Relevant Website

    Chapter 151. Cutaneous Hamartoneoplastic Disorders

    151.1 Introduction

    151.2 Hereditary Leiomyomatosis and Renal-Cell Cancer

    151.3 Birt–Hogg–Dubé Syndrome

    References

    Relevant Web pages

    Chapter 152. Inherited Disorders of the Hair

    Glossary

    152.1 Introduction and Hair Anatomy

    152.2 HF Morphogenesis and Cycling

    152.3 The Hair Keratins and their Regulation

    152.4 Desmosomes of the HF

    152.5 Genetics of Hypotrichosis and Other Structural Hair Abnormalities

    152.6 Hair Abnormalities in Association with Metabolic Diseases

    152.7 Other Disorders Associated with Hair Phenotypes

    152.8 Hypertrichosis

    152.9 Genetics of Polygenic Diseases

    Acknowledgments

    References

    Dermatologic Disorders

    Chapter 153. Marfan Syndrome and Related Disorders

    153.1 Introduction

    153.2 Structure and Composition of Extracellular Microfibrils

    153.3 Fibrillins

    153.4 Functions of Microfibrils

    153.5 Marfan Syndrome (OMIM ∗154700): The Prototype of Disorders of Microfibrilogenesis and the Fibrillins

    153.6 Disorders Related to Marfan Syndrome through Phenotype, Etiology or Pathogenesis

    Acknowledgments

    References

    Chapter 154. Ehlers–Danlos Syndrome

    154.1 Introduction

    154.2 Collagen Genes and Proteins

    154.3 Biosynthesis of Collagens

    154.4 Classical Ehlers–Danlos Syndrome (Types I and II—GRAVIS and Mitis)

    154.5 Hypermobile Type (EDS Type III—Familial Hypermobility)

    154.6 Vascular, Ecchymotic Type (EDS Type IV)

    154.7 Kyphyoscoliotic Ehlers–Danlos Syndrome (EDS Type VI)

    154.8 Arthrochalasis Types of Ehlers–Danlos Syndrome (EDS Types VIIA and VIIB)

    154.9 Dermatosparaxis (EDS Type VIIC)

    154.10 Other Forms of Ehlers–Danlos Syndrome

    154.11 Summary

    References

    Chapter 155. Heritable Diseases Affecting the Elastic Fibers: Cutis Laxa, Pseudoxanthoma Elasticum, and Related Disorders

    155.1 Introduction

    155.2 Biology of Elastin

    155.3 Elastin Deficiency Disorders

    155.4 Elastin Accumulation Diseases

    155.5 Disorders of Elastin Fibrillogenesis

    Acknowledgments

    References

    Connective Tissue Disorders

    Chapter 156. Osteogenesis Imperfecta (and Other Disorders of Bone Matrix)

    Glossary

    156.1 Introduction

    156.2 Osteogenesis Imperfecta

    156.3 Management of Osteogenesis Imperfecta

    156.4 Clinical Features of the OI Syndromes

    156.5 Other Manifestations of Osteogenesis Imperfecta

    156.6 Syndromes with Osteoporosis and Eye Disease

    156.7 Hypophosphatasia

    156.8 Other Bone Fragility Disorders

    References

    Chapter 157. Disorders of Bone Density, Volume, and Mineralization

    157.1 Introduction

    157.2 Osteopetrosis Group of Disorders

    157.3 Raine Dysplasia

    157.4 Pyknodysostosis

    157.5 Dysosteosclerosis

    157.6 Osteopoikilosis, Buschke–Ollendorf Syndrome, and Melorheostosis

    157.7 Osteopathia Striata

    157.8 Craniotubular Remodeling Disorders

    157.9 Craniotubular Remodeling Disorders Resulting From Mutations in Filamin a

    157.10 Tubular Stenosis (Kenny–Caffey Syndrome)

    157.11 Hyperphosphatasemia with Osteoectasia

    157.12 Disorders of Parathyroid Hormone Resistance

    157.13 X-linked Hypophosphatemic Rickets

    References

    Chapter 158. Chondrodysplasias

    158.1 Introduction

    158.2 Classification and Nomenclature

    158.3 Clinical Evaluation

    158.4 Radiologic Evaluation

    158.5 Chondro-osseous Morphology

    158.5 Biochemical and Molecular Abnormalities

    158.6 Summary

    References

    Further Reading

    Chapter 159. Abnormalities of Bone Structure

    Glossary

    159.1 Introduction

    159.2 Dysplasia Epiphysealis Hemimelica

    159.3 Hereditary Multiple Exostoses

    159.4 Langer–Giedion Syndrome

    159.5 Enchondromatosis

    159.6 Maffucci Syndrome

    159.7 Metachondromatosis

    159.8 Fibrous Dysplasia of Bone

    159.9 Cherubism

    References

    Relevant Websites

    Chapter 160. The Dysostoses

    160.1 Introduction

    160.2 Dysostoses with Predominantly Axial Involvement

    160.3 Predominant Limb Involvement

    160.4 Predominant Limb Involvement with Other Associated Abnormalities

    References

    Further reading

    Chapter 161. Arthrogryposes (Multiple Congenital Contractures)

    161.1 Introduction

    161.2 Approach

    161.3 Differential Diagnosis

    161.4 Frequently Observed Conditions

    161.8 Summary

    References

    Relevant Websites

    Chapter 162. Common Skeletal Deformities

    162.1 Introduction

    162.2 Idiopathic Scoliosis

    162.3 Spondylolisthesis

    162.4 Congenital Dislocation of the HIP

    162.5 Clubfoot

    162.6 Juvenile Osteochondroses

    References

    Relevant Website

    Chapter 163. Hereditary Noninflammatory Arthropathies

    163.1 Introduction

    163.2 Spondyloepiphyseal Dysplasias

    163.3 Familial Osteoarthropathy

    163.4 Primary Osteoarthropathy of the Hip

    163.5 Mseleni Joint Disease

    Acknowledgments

    References

    Skeletal Disorders

    Chapter 164. Pathways—Cohesinopathies

    164.1 Introduction

    164.2 Clinical Features of CdLS

    164.3 Diagnosis

    164.4 Genetics

    164.5 Other Disorders of Cohesin and Sister Chromatid Cohesion

    References

    Chapter 165. Genes and Mechanisms in Human Ciliopathies

    Glossary

    165.1 Cilia Structure and Function

    165.2 Clinical Aspects of Ciliopathies and Ciliopathy-Like Disorders

    165.3 Clinical Aspects of Ciliopathies

    165.4 Molecular and Developmental Mechanisms in Ciliopathies

    165.5 Direct Interactions between Ciliopathy Proteins and Evidence for Complex Inheritance in a Subset of Families

    Supplementary Data

    Acknowledgments

    References

    Relevant Website

Product details

  • No. of pages: 4700
  • Language: English
  • Copyright: © Academic Press 2013
  • Published: February 28, 2013
  • Imprint: Academic Press
  • eBook ISBN: 9780123838353

About the Editors

David Rimoin

Affiliations and Expertise

Medical Genetics Institute, Los Angeles, CA, USA

Reed Pyeritz

Dr. Reed Pyeritz is a medical genetics doctor in Philadelphia, Pennsylvania and is affiliated with Hospitals of the University of Pennsylvania-Penn Presbyterian. Dr. Pyeritz focuses his research in two areas – Mendelian disorders of the cardiovascular system (especially those involving defects of connective tissue) and ethical, legal and social implications of human genetics. He is continuing his studies, begun over 20 years ago, of Marfan syndrome and related conditions – diseases in which the aorta and occasionally major arterial branches gradually enlarge and dissect, leading to early demise if untreated. Current efforts include a multicenter trial of angiotensin receptor blockade in Marfan syndrome, the identification of additional genes that predispose to arteriopathy, and improving methods for diagnosing and treating arterio-venous malformations, especially in hereditary hemorrhagic telangiectasia (HHT). Dr. Pyeritz directs Penn CIGHT (Center for the Integration of Genetic Healthcare Technologies). Supported by the ELSI Branch of the National Human Genome Research Institute, Penn CIGHT conducts research in the broad area of ‘uncertainty’ as related to the introduction of evolving approaches to assaying a patient’s genotype.

Affiliations and Expertise

William Smilow Professor of Medicine and Professor of Genetics, Senior Fellow, Leonard Davis Institute of Health Economics, Perelman School of Medicine, University of Pennsylvania, Smilow Center for Translational Research, Philadelphia, PA, USA

Bruce Korf

Affiliations and Expertise

University of Alabama at Birmingham, Birmingham, AL

Ratings and Reviews

Write a review

There are currently no reviews for "Emery and Rimoin's Principles and Practice of Medical Genetics"