Genomics in the Clinic

A Practical Guide to Genetic Testing, Evaluation, and Counseling

1st Edition - November 4, 2023
Editors: Antonie D. Kline, Ethylin Wang Jabs
Language: English
Paperback ISBN:
9 7 8 - 0 - 1 2 - 8 1 6 4 7 8 - 5
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 1 6 4 7 9 - 2

Genomics in the Clinic: A Practical Guide to Genetic Testing, Evaluation, and Counseling illustrates the current scope of the practice of genetics for healthcare profes… Read more

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Genomics in the Clinic: A Practical Guide to Genetic Testing, Evaluation, and Counseling illustrates the current scope of the practice of genetics for healthcare professionals, so they can understand principles applicable to genetic testing and consultation. Written by an authoritative well-balanced team, including experienced clinical geneticists, genetic counselors, and medical subspecialists, this book adopts an accessible, easy-to-follow format. Sections are dedicated to basic genetic principles; clinical genetic and genomic testing; prenatal, clinical and cancer genetic diagnosis and counseling; and ethical and social implications in genomic medicine. Over 100 illustrative cases examine a range of prenatal, pediatric and adult genetic conditions and testing, putting these concepts and approaches into practice. Genomics in the Clinic: A Practical Guide to Genetic Testing, Evaluation, and Counseling is important for primary care providers, as patient care evolves in the current genomic-influenced world of precision medicine.

Cover image
Title page
Table of Contents
Copyright
Dedication
Contributors
Foreword
Acknowledgments
Chapter 1. Introduction
Chapter 2. Basic Principles of Genetics and Genomics
2.1. Chromosome Structure and Function
2.2. Chromosome Variation
2.3. Molecular Structure and Function
2.4. Molecular Variation
2.5. Mitochondrial Structure and Function
2.6. Epigenome
2.7. Modes of Inheritance
2.8. Phenotypic Variation
Chapter 3. Genetic Counseling and Referrals
3.1. Preparation for Genetics Appointment
3.2. Family History and Genetic Background
3.3. Genetic Counseling
3.4. Genetic Risks for Family Members
3.5. Psychosocial Issues and Support Organizations
Chapter 4. Prenatal Genetics and Referrals
4.1. Carrier Screening
4.2. High-risk Pregnancy
4.3. Fetal Imaging
4.4. Prenatal Evaluation
4.5. Other Reproductive Options
Chapter 5. Clinical Genetics and Referrals
5.1. Congenital Anomalies and Dysmorphic Features
5.2. Developmental Disabilities and Behavioral Abnormalities
5.3. Growth Disorders
5.4. Metabolic Disorders
5.5. Adult Onset Conditions
5.6. Pharmacogenomic Testing
5.7. Genetics of Mental Illness
Chapter 6. Genetic and Genomic Testing
6.1. Cytogenetics and Cytogenetic Testing
6.2. Genotyping
6.3. Genome Testing
6.4. Other Specific Tests
6.5. Source of Sample (Blood, Saliva, Tissue)
6.6. Ordering Genetic and Genomic Tests
Chapter 7. Genetic and Genomic Results and Management
7.1. Interpretation of Results
7.2. Recommendations for Reporting Secondary Findings
7.3. Limitations of Genetic Testing
7.4. Management and Services Available with Genetic Diagnosis
Chapter 8. Cancer Genetics Referrals and Management
8.1. Hereditary Cancer Risk Assessment
8.2. Referral for Cancer Genetic Testing
8.3. Management Recommendations for Mutation-Positive Individuals
8.4. Follow-up after Cancer Genetic Testing
Chapter 9. Direct-to-Consumer Testing
9.1. Direct-to-Consumer Testing and Limitations
9.2. Ethical Considerations
9.3. Medical and Scientific Considerations
9.4. Risk and Benefits
9.5. Conclusions
Chapter 10. Ethical and Psychosocial Issues
10.1. The Informed Consent Process
10.2. Cost and Insurance Concerns
10.3. Secondary and Incidental Findings
10.4. Genetic Information Nondiscrimination Act
10.5. Reinterpretation of Findings and Patient Recontact
Chapter 11. Case Scenarios
Section 11.1. Prenatal Cases
Case 11.1.1. Prenatal Cases: Positive Carrier Screening in Pregnancy
The Case
The Issues
The Referral
The Diagnosis
Case 11.1.2. Prenatal Cases: Maternal Diabetes Exposure
The Case
The Issues
The Referral
The Diagnosis
Case 11.1.3. Prenatal Cases: Advanced Maternal Age
The Case
The Issues
The Referral
The Diagnosis
Case 11.1.4. Prenatal Cases: Noninvasive Prenatal Screening Positive for Sex Chromosome Abnormality
The Case
The Issues
The Referral
The Diagnosis
Case 11.1.5. Prenatal Cases: Fetal Anomalies
The Case
The Issues
The Referral
The Diagnosis
Case 11.1.6. Prenatal Cases: Clubfeet and Decreased Fetal Movement
The Case
The Issues
The Referral
The Diagnosis
Case 11.1.7. Prenatal Cases: Recurrent Pregnancy Loss
The Case
The Issues
The Referral
The Diagnosis
Case 11.1.8. Prenatal Cases: Preimplantation Genetic Testing for a Single Gene Disorder
The Case
The Issues
The Referral
The Diagnosis
Section 11.2. Newborn Screening Cases
Case 11.2.1. Newborn Screening Cases: False Positive Newborn Screening
The Case
The Issues
The Referral
The Diagnosis
Case 11.2.2. Newborn Screening Cases: Abnormal Newborn Metabolic Screening
The Case
The Issues
The Referral
The Diagnosis
Case 11.2.3. Newborn Screening Cases: Abnormal Newborn Hearing Screening
The Case
The Issues
The Referral
The Diagnosis
Case 11.2.4. Newborn Screening Cases: Abnormal Newborn Neuromuscular Screening
The Case
The Issues
The Referral
The Diagnosis
Section 11.3. Craniofacial Cases
Case 11.3.1. Craniofacial Cases: Congenital Microcephaly
The Case
The Issues
The Referral
The Diagnosis
Case 11.3.2. Craniofacial Cases: Misshapen Head
The Case
The Issues
The Referral
The Diagnosis
Case 11.3.3. Craniofacial Cases: Congenital Nystagmus
The Case
The Issues
The Referral
The Diagnosis
Case 11.3.4. Craniofacial Cases: Loss of Central Vision
The Case
The Issues
The Referral
The Diagnosis
Case 11.3.5. Craniofacial Cases: Bilateral Retinal Detachment
The Case
The Issues
The Referral
The Diagnosis
Case 11.3.6. Craniofacial Cases: Acquired Night Blindness
The Case
The Issues
The Referral
The Diagnosis
Case 11.3.7. Craniofacial Cases: Congenital Hearing Loss
The Case
The Issues
The Referral
The Diagnosis
Case 11.3.8. Craniofacial Cases: Hearing Loss and Renal Agenesis
The Case
The Issues
The Referral
The Diagnosis
Case 11.3.9. Craniofacial Cases: Hearing Loss and Night Blindness in a Teenager
The Case
The Issues
The Referral
The Diagnosis
Case 11.3.10. Craniofacial Cases: Cleft Palate
The Case
The Issues
The Referral
The Diagnosis
Section 11.4. Cardiovascular and Pulmonary Cases
Case 11.4.1. Cardiovascular and Pulmonary Cases: Recurrent Pneumonias
The Case
The Issues
The Referral
The Diagnosis
Case 11.4.2. Cardiovascular and Pulmonary Cases: Dyspnea with History of Neonatal Jaundice
The Case
The Issues
The Referral
The Diagnosis
Case 11.4.3. Cardiovascular and Pulmonary Cases: Pulmonic Stenosis and Short Stature
The Case
The Issues
The Referral
The Diagnosis
Case 11.4.4. Cardiovascular and Pulmonary Cases: Severe Palpitations
The Case
The Issues
The Referral
The Diagnosis
Case 11.4.5. Cardiovascular and Pulmonary Cases: Exercise-Induced Syncope
The Case
The Issues
The Referral
The Diagnosis
Case 11.4.6. Cardiovascular and Pulmonary Cases: Hyperlipidemia
The Case
The Issues
The Referral
The Diagnosis
Case 11.4.7. Cardiovascular and Pulmonary Cases: Myocardial Infarction in a Healthy Adult
The Case
The Issues
The Referral
The Diagnosis
Case 11.4.8. Cardiovascular and Pulmonary Cases: Cardiomyopathy and Peripheral Neuropathy
The Case
The Issues
The Referral
The Diagnosis
Section 11.5. Gastrointestinal Cases
Case 11.5.1. Gastrointestinal Cases: Bowel Obstruction in an Infant
The Case
The Issues
The Referral
The Diagnosis
Case 11.5.2. Gastrointestinal Cases: Elevated Liver Transaminases in an Infant
The Case
The Issues
The Referral
The Diagnosis
Case 11.5.3. Gastrointestinal Cases: Failure to Thrive
The Case
The Issues
The Referral
The Diagnosis
Case 11.5.4. Gastrointestinal Cases: Obesity, Hypotonia, and Peripheral Vision Loss
The Case
The Issues
The Referral
The Diagnosis
Case 11.5.5. Gastrointestinal Cases: Acute Abdominal Pain
The Case
The Issues
The Referral
The Diagnosis
Case 11.5.6. Gastrointestinal Cases: Abdominal Pain and Arthralgias
The Case
The Issues
The Referral
The Diagnosis
Section 11.6. Metabolic Cases
Case 11.6.1. Metabolic Cases: Sweet Smell in an Infant
The Case
The Issues
The Referral
The Diagnosis
Case 11.6.2. Metabolic Cases: Apparent Life-Threatening Event
The Case
The Issues
The Referral
The Diagnosis
Case 11.6.3. Metabolic Cases: Hypoglycemia in a Child
The Case
The Issues
The Referral
The Diagnosis
Case 11.6.4. Metabolic Cases: Recurrent Vomiting and Language Delay
The Case
The Issues
The Referral
The Diagnosis
Case 11.6.5. Metabolic Cases: Lactic Acidosis
The Case
The Issues
The Referral
The Diagnosis
Case 11.6.6. Metabolic Cases: Hunger and Protein Intake in a Metabolic Condition
The Case
The Issues
The Referral
The Diagnosis
Section 11.7. Endocrinologic and Growth Cases
Case 11.7.1. Endocrinologic and Growth Cases: Overgrowth
The Case
The Issues
The Referral
The Diagnosis
Case 11.7.2. Endocrinologic and Growth Cases: Macrocephaly and Tall Stature in a Toddler
The Case
The Issues
The Referral
The Diagnosis
Case 11.7.3. Endocrinologic and Growth Cases: Diabetes
The Case
The Issues
The Referral
The Diagnosis
Case 11.7.4. Endocrinologic and Growth Cases: Short Stature
The Case
The Issues
The Referral
The Diagnosis
Case 11.7.5. Endocrine and Growth Cases: Small Stature and Delayed Puberty
The Case
The Issues
The Referral
The Diagnosis
Case 11.7.6. Endocrine and Growth Cases: Pubertal Delay, Hearing Loss, and Lack of Smell
The Case
The Issues
The Referral
The Diagnosis
Section 11.8. Genitourinary Cases
Case 11.8.1. Genitourinary Cases: Ambiguous Genitalia
The Case
The Issues
The Referral
The Diagnosis
Case 11.8.2. Genitourinary Cases: Familial Renal Disease
The Case
The Issues
The Referral
The Diagnosis
Case 11.8.3. Genitourinary Cases: Renal Cysts
The Case
The Issues
The Referral
The Diagnosis
Section 11.9. Hematologic and Immunologic Cases
Case 11.9.1. Hematologic and Immunologic Cases: Bleeding Disorder
The Case
The Issues
The Referral
The Diagnosis
Case 11.9.2. Hematologic and Immunologic Cases: Recurrent Infections in Childhood
The Case
The Issues
The Referral
The Diagnosis
Case 11.9.3. Hematologic and Immunologic Cases: Chronic Thrombocytopenia in a Child
The Case
The Issues
The Referral
The Diagnosis
Case 11.9.4. Hematologic and Immunologic Cases: Thrombocytopenia in an Adult
The Case
The Issues
The Referral
The Diagnosis
Case 11.9.5. Hematologic and Immunologic Cases: Bone Marrow Failure
The Case
The Issues
The Referral
The Diagnosis
Section 11.10. Skeletal and Connective Tissue Cases
Case 11.10.1. Skeletal and Connective Tissue Cases: Asymmetric Leg Size in an Infant
The Case
The Issues
The Referral
The Diagnosis
Case 11.10.2. Skeletal and Connective Tissue Cases: Disproportionate Short Stature
The Case
The Issues
The Referral
The Diagnosis
Case 11.10.3. Skeletal and Connective Tissue Cases: Multiple Fractures
The Case
The Issues
The Referral
The Diagnosis
Case 11.10.4. Musculoskeletal Cases: Tall and Lean with Nonspecific Hip Pain
The Case
The Issues
The Referral
The Diagnosis
Case 11.10.5. Musculoskeletal Cases: Chronic Musculoskeletal Pain and Fatigue
The Case
The Issues
The Referral
The Diagnosis
Section 11.11. Dermatologic Cases
Case 11.11.1. Dermatologic Cases: Infant with Nystagmus and Fair Skin
The Case
The Issues
The Referral
The Diagnosis
Case 11.11.2. Dermatologic Cases: Multiple Café au Lait Spots
The Case
The Issues
The Referral
The Diagnosis
Case 11.11.3. Dermatologic Cases: Abnormal Teeth in a Toddler
The Case
The Issues
The Referral
The Diagnosis
Section 11.12. Neurodevelopmental Cases
Case 11.12.1. Neurodevelopmental Cases: Developmental Stagnation and Regression
The Case
The Issues
The Referral
The Diagnosis
Case 11.12.2. Neurodevelopmental Cases: Delayed Speech, Polydactyly, and Short Stature
The Case
The Issues
The Referral
The Diagnosis
Case 11.12.3. Neurodevelopmental Cases: Delayed Development in Early Childhood
The Case
The Issues
The Referral
The Diagnosis
Case 11.12.4. Neurodevelopmental Cases: Autism Spectrum Disorder
The Case
The Issues
The Referral
The Diagnosis
Case 11.12.5. Neurodevelopmental Cases: Cognitive Issues and Tall Stature
The Case
The Issues
The Referral
The Diagnosis
Section 11.13. Neurologic and Muscular Cases
Case 11.13.1. Neurologic and Muscular Cases: Congenital Hypotonia and Feeding Difficulties
The Case
The Issues
The Referral
The Diagnosis
Case 11.13.2. Neurologic and Muscular Cases: Dysmorphic Features and Hypotonia
The Case
The Issues
The Referral
The Diagnosis
Case 11.13.3. Neurologic and Muscular Cases: Seizures in an Infant
The Case
The Issues
The Referral
The Diagnosis
Case 11.13.4. Neurologic and Muscular Disease: Clubfeet and Lack of Facial Expression
The Case
The Issues
The Referral
The Diagnosis
Case 11.13.5. Neurologic and Muscular Cases: Abnormal Gait in a Toddler
The Case
The Issues
The Referral
The Diagnosis
Case 11.13.6. Neurologic and Muscular Cases: Abnormal Movements and Posturing
The Case
The Issues
The Referral
The Diagnosis
Case 11.13.7. Neurologic and Muscular Cases: Dystonia Family History
The Case
The Issues
The Referral
The Diagnosis
Case 11.13.8. Neurologic and Muscular Cases: Slowness and Loss of Facial Expression in a Young Adult
The Case
The Issues
The Referral
The Diagnosis
Case 11.13.9. Neurologic and Muscular Cases: Progressive Gait Impairment and Genitourinary Dysfunction
The Case
The Issues
The Referral
The Diagnosis
Case 11.13.10. Neurologic and Muscular Cases: Progressive Ataxia
The Case
The Issues
The Referral
The Diagnosis
Case 11.13.11. Neurologic and Muscular Cases: Intention Tremor and Difficulty with Balance
The Case
The Issues
The Referral
The Diagnosis
Case 11.13.12. Neurologic and Muscular Cases: Chorea
The Case
The Issues
The Referral
The Diagnosis
Section 11.14. Psychiatric Cases
Case 11.14.1. Psychiatric Cases: Early-Onset Dementia
The Case
The Issues
The Referral
The Diagnosis
Cases 11.14.2. Psychiatric Cases: Psychosis and Learning Disabilities
The Case
The Issues
The Referral
The Diagnosis
Case 11.14.3. Psychiatric Cases: Bipolar Disorder and Stevens–Johnson Syndrome
The Case
The Issues
The Referral
The Diagnosis
Section 11.15. Pharmacogenomic Cases
Case 11.15.1. Pharmacogenomic Cases: Warfarin for Atrial Fibrillation
The Case
The Issues
The Referral
The Diagnosis
Case 11.15.2. Pharmacogenomic Cases: Clopidogrel for Coronary Artery Disease
The Case
The Issues
The Referral
The Diagnosis
Case 11.15.3. Pharmacogenomic Cases: Thiopurine for Acute Lymphoblastic Leukemia
The Case
The Issues
The Referral
The Diagnosis
Section 11.16. Cancer Cases
Case 11.16.1. Cancer Cases: Breast Cancer Gene Mutation Found Incidentally
The Case
The Issues
The Referral
The Diagnosis
Case 11.16.2. Cancer Cases: Ovarian Cancer Family History
The Case
The Issues
The Referral
The Diagnosis
Case 11.16.3. Cancer Cases: Family History of Lynch Syndrome
The Case
The Issues
The Referral
The Diagnosis
Case 11.16.4. Cancer Cases: Prostate Cancer
The Case
The Issues
The Referral
The Diagnosis
Case 11.16.5. Cancer Cases: Pancreatic Cancer
The Case
The Issues
The Referral
The Diagnosis
Case 11.16.6. Cancer Cases: Adrenocortical Carcinoma and Leukemia
The Case
The Issues
The Referral
The Diagnosis
Case 11.16.7. Cancer Cases: Macrocytic Anemia and Idiopathic Pulmonary Fibrosis
The Case
The Issues
The Referral
The Diagnosis
Section 11.17. Direct-to-Consumer Cases
Case 11.17.1. Direct-to-Consumer Cases: Breast Cancer Family History
The Case
The Issues
The Referral
The Diagnosis
Case 11.17.2. Direct to Consumer Cases: Predisposition of a Multifactorial Condition by Direct-to-Consumer Testing
The Case
The Issues
The Referral
The Diagnosis
Case 11.17.3. Direct-to-Consumer Cases: Identification of Birth Family History by Direct-to-Consumer Testing
The Case
The Issues
The Referral
The Diagnosis
Case 11.17.4. Direct-to-Consumer Cases: Metabolic and Neurologic Disease Risk by Direct-to-Consumer Testing
The Case
The Issues
The Referral
The Diagnosis
Case 11.17.5. Direct-to-Consumer Cases: Risk for Late-Onset Alzheimer Disease by Direct-to-Consumer Testing
The Case
The Issues
The Referral
The Diagnosis
Case 11.17.6. Direct-to-Consumer Cases: Wellness Report By Direct-to-Consumer Testing
The Case
The Issues
The Referral
The Diagnosis
Section 11.18. Ethical Issues Cases
Case 11.18.1. Ethical Issues Cases: Predictive Testing in an Adolescent with Positive Family History
The Case
The Issues
The Referral
The Diagnosis
Case 11.18.2. Ethical Issues Cases: Preconception Sex Selection
The Case
The Issues
The Referral
The Diagnosis
Section 12. Communicating Genetics and Genomics
Chapter 12. Communicating Genetics and Genomics
12.1. Overview of Genetic Discussion with Families
12.2. Counseling about Genetic Concepts
12.3. Counseling about Genetic Tests
12.4. Counseling about Results
12.5. Concluding Remarks
12.6. Visual Aids to Explain Genetic Concepts to Families
Index

Antonie D. Kline

Dr. Kline received her medical degree from Jefferson Medical College, Philadelphia, Pa., her postdoctoral training in medical genetics at Jefferson Medical College, Philadelphia, PA, her clinical cytogenetics training at the Kennedy Krieger Institute of the Johns Hopkins University School of Medicine, Baltimore, Md. She is board-certified in clinical genetics, clinical cytogenetics and clinical molecular genetics. She is also a Fellow of the American Academy of Pediatrics and a Founding Fellow of the American College of Medical Genetics. Dr. Kline is the medical director of the Cornelia de Lange Syndrome Foundation and a member of the professional advisory board of the 5p- Society. Her areas of expertise include evaluation of multiple birth defects and/or developmental issues, as well as correlation and interpretation of cytogenetic changes in a clinical setting.

Affiliations and expertise

Director of Clinical Genetics, Harvey Institute for Medical Genetics, Greater Baltimore Medical Center, Towson, MD, USA

Ethylin Wang Jabs

Dr. Ethylin Wang Jabs is a clinical geneticist and serves as an attending in medical genetics in the General Genetics Clinic and the Cleft and Craniofacial Clinic at the Mount Sinai Medical Center, New York, NY. Dr. Jabs is also Vice Chair and Professor of the Department of Genetics and Genomic Sciences, Professor of Pediatrics, and Professor of Developmental and Regenerative Biology at Mount Sinai. She was the Chief of the Division of Medical Genetics and Genomics from 2007-2012 and served as Director of the Medical Genetics Residency and Clinical Laboratory Fellowship Training Programs from 2007-2011. Prior to November 1, 2007, her appointment was at Johns Hopkins University School of Medicine. She was the Dr. Frank V. Sutland Professor of Pediatric Genetics, Director of the Center for Craniofacial Development and Disorders, and Director of the International Collaborative Genetics Research Training Program.

Affiliations and expertise

Chair, Department of Clinical Genomics, Mayo Clinic, Rochester, Minnesota, USA; Adjunct Professor, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Adjunct Professor, Department of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA

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