Emery and Rimoin's Principles and Practice of Medical Genetics - 6th Edition - ISBN: 9780123838346, 9780123838353

Emery and Rimoin's Principles and Practice of Medical Genetics

6th Edition

Editors: David Rimoin Reed Pyeritz Bruce Korf
Hardcover ISBN: 9780123838346
eBook ISBN: 9780123838353
Imprint: Academic Press
Published Date: 28th February 2013
Page Count: 4700
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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


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



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


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


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


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



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


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



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?



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


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



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


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


Cross 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


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


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


Cross 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


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


Cross 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


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


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



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


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


Cross 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


Cross 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


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



Chapter 25. Prenatal Screening for Neural Tube Defects and Aneuploidy

25.1 Introduction

25.2 Neural Tube Defects

25.3 Aneuploidy

25.4 Summary


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


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



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




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


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”


Further Reading



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)


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


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


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


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


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


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


Chapter 38. Abnormal Body Size and Proportion

38.1 Introduction

38.2 Pathologic Short Stature

38.3 Pathologic Overgrowth



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


Chapter 40. Transplantation Genetics


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



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


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


Applications to Specific Disorders


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


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


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


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




Chapter 47. Inherited Cardiomyopathies

47.1 Introduction

47.2 Hypertrophic Cardiomyopathy

47.3 Dilated Cardiomyopathy

47.4 Atypical Cardiomyopathies

47.5 Conclusion

Cross 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




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



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



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


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



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


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


Chapter 55. Genetics of Atherosclerotic Cardiovascular Disease


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


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



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


Cross 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



Chapter 59. Genetic Underpinnings of Asthma and Related Traits



59.1 Introduction

59.2 The Genetics of Asthma and Allergic Diseases

59.3 Conclusion


Cross References


Relevant web pages

Chapter 60. Hereditary Pulmonary Emphysema


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



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


Respiratory Disorders

Chapter 62. Congenital Anomalies of the Kidney and Urinary Tract


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


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


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


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


Further Reading

Cross References

Chapter 66. Cancer of the Kidney and Urogenital Tract


66.1 Tumors of the Kidney

66.2 Bladder Neoplasms

66.3 Carcinoma of the Prostate

66.4 Testicular Neoplasms


Cross References

Renal Disorders

Chapter 67. Gastrointestinal Tract and Hepatobiliary Duct System


67.1 Introduction

67.2 Embryological Background

67.3 Classification of Gastrointestinal Disorders


Relevant Web Pages

Chapter 68. Inflammatory Bowel Disease


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


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



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


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


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


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


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


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


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


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


Further Reading

Chapter 78. Rheumatoid Disease and Other Inflammatory Arthropathies


78.1 Introduction

78.2 Rheumatoid Arthritis

78.3 Seronegative Spondyloarthropathies

78.4 Juvenile Idiopathic Arthritis


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


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


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


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


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


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


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



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


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



Further Reading

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

88.1 Introduction

88.2 46,XX Disorders of Sexual Development


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


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


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


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


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


Cross 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


Further Reading

Chapter 95. Purine and Pyrimidine Metabolism


95.1 Introduction

95.2 Purine Metabolism

95.3 Pyrimidine Metabolism


Cross Reference


Further Reading

Chapter 96. Lipoprotein and Lipid Metabolism


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


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


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


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


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



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


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


Relavent Web Sites

Further Reading

Chapter 103. Oligosaccharidoses: Disorders Allied to the Oligosaccharidoses

103.1 Oligosaccharidoses

103.2 Disorders Allied to Oligosaccharidoses



Relevant Webpages

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


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



Chapter 105. Peroxisomal Disorders


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


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


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


Further Reading

Chapter 108. Dyslexia and Related Communication Disorders


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


Chapter 109. Attention-Deficit/Hyperactivity Disorder

109.1 Behavioral Genetics

109.2 Molecular Genetics

109.3 Conclusions

Cross 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


Chapter 111. Genetics of Alzheimer Disease

111.1 Background and History

111.2 Genetics of EOAD

111.3 Genetics of LOAD


Further Reading

Chapter 112. Schizophrenia and Affective Disorders


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


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


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



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


Cross References


Further Reading

List of Relevant Web Pages

Chapter 116. Genetic Aspects of Human Epilepsy


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


Cross 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


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


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




Chapter 120. Autonomic and Sensory Disorders

120.1 Introduction

120.2 Familial Dysautonomia

120.3 Congenital Sensory Neuropathy with Anhidrosis (HSAN Type IV)


Chapter 121. The Phakomatoses

121.1 Introduction

121.2 The Neurofibromatoses



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


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



Chapter 124. Primary Tumors of the Nervous System


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


Relevant Webpages

Further Reading

Neurologic Disorders

Chapter 125. Muscular Dystrophies


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


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


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



Chapter 128. Spinal Muscular Atrophies

128.1 Introduction: Definition

128.2 Proximal Spinal Muscular Atrophy

128.3 Nonproximal Spinal Muscular Atrophy

128.4 Management


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



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


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


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


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




Further Reading

Chapter 134. Optic Atrophy


134.1 Introduction

134.2 “Primary” Optic Atrophies

134.3 Complex Optic Atrophies


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


Further Reading

Chapter 136. Defects of the Cornea


136.1 Introduction

136.2 Dystrophies

136.3 Defects Associated with Systemic Disease

136.4 Other Inherited Corneal Abnormalities

136.5 Conclusion


Chapter 137. Congenital Cataracts and Genetic Anomalies of the Lens


137.1 Introduction

137.2 Noncataractous Anomalies

137.3 Cataracts

137.4 Therapy



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


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


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


Further Reading

Chapter 141. Anophthalmia, Microphthalmia, and Uveal Coloboma


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


Further Reading

Relevant Websites

Ophthalmologic Disorders

Chapter 142. Hereditary Hearing Impairment



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


Further reading


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


Chapter 144. Craniosynostosis


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


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



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


Further Reading

Chapter 147. Epidermolysis Bullosa


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


Further Reading

List of Websites Relavant to EB

Chapter 148. Ectodermal Dysplasias


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


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


Chapter 150. Psoriasis


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


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


Relevant Web pages

Chapter 152. Inherited Disorders of the Hair


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



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



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


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



Connective Tissue Disorders

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


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


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


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


Further Reading

Chapter 159. Abnormalities of Bone Structure


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


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


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


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


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



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


Chapter 165. Genes and Mechanisms in Human Ciliopathies


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



Relevant Website


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© Academic Press 2013
Academic Press
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About the Editor

David Rimoin

Affiliations and Expertise

Medical Genetics Institute, Los Angeles, CA, USA

Reed Pyeritz

Affiliations and Expertise

University of Pennsylvania School of Medicine, Philadelphia, PA, USA

Bruce Korf

Affiliations and Expertise

University of Alabama at Birmingham, Birmingham, AL


Praise for previous editions

"...the most comprehensive review of genetic knowledge applied to the clinical practice of medical genetics [...] This is a book of magnificent quality. Very few books can be compared to this one. This is a must-have textbook with features that make it a unique source for medical geneticists" Luis F. Escobar, Shock, 2008;30-3:339 doi: 10.1097/01.SHK.0000286299.94327.fa

...to have brought together between the covers of three volumes a comprehensive summary of current thoughts and practices in clinical genetics as practised in the leading departments across the world by some of the greatest geneticists is a magnificent achievement. It is a body of experience from which we can all learn and to which I suspect most of us will continue to turn on a regular basis" Willie Reardon, J Med Genet 2002;39:454 doi:10.1136/jmg.39.6.454-a