Clinical Genetics and Genomics at a Glance

Citation

Lakhani, N., Kulkarni, K., Barwell, J., Vasudevan, P., & Dorkins, H. (Eds.). (2023). Clinical Genetics and Genomics at a Glance. Wiley-Blackwell.

Chapter Summary

This first edition is an edited, multi-contributor volume of 272 pages, with 99 chapters in 14 parts, a foreword, a preface, a glossary and an index. After a five-chapter introduction the book is organised by body system and specialty, and almost every chapter after Part 1 is devoted to a single condition or group of conditions. Chapters follow the At a Glance pattern of short, illustrated units, but they are not uniform in length: the contents show some one-page chapters and others of three or four pages. The editors are clinical geneticists and clinicians based at University Hospitals of Leicester, together with an Oxford medical tutor who edits the Journal of Medical Genetics; the sample chapter is written from within the UK National Health Service.

Part 1: Introduction (Chapters 1–5)

What is clinical genetics and genomic medicine?; Inheritance; Cytogenetics and molecular genetic techniques; How to read a genetic test report; Genetic and genomic counselling. The sample Chapter 1, published by Wiley, defines the work of clinical geneticists (diagnosis and management of families with chromosomal, congenital, single-gene and familial cancer conditions), explains pedigree drawing and the growing importance of variant interpretation, discusses genetic testing and insurance in the UK, and divides genomic medicine into personalised medicine, integrated care and population data science, listing six areas that go beyond classical single-gene genetics, from genome-wide association studies and pharmacogenetics to tumour DNA testing and epigenetics. Chapters 2–5 supply the remaining tools: inheritance patterns, laboratory techniques, reading a test report, and counselling.

Part 2: Cardiology (Chapters 6–9)

Structural and congenital heart disease; Cardiomyopathies; Ischaemic heart disease; Arrhythmias and sudden cardiac death. Inherited cardiac conditions, including those with a risk of sudden death, are a group that Chapter 1 names among the conditions clinical geneticists manage.

Part 3: Dermatology (Chapters 10–20)

Tuberous sclerosis complex; Gorlin syndrome; Darier's disease; Lamellar ichthyosis; Mal de Meleda; Cutaneous porphyria; Cowden syndrome and Cowden-like syndrome; Epidermolysis bullosa; Muir-Torre syndrome; X-linked ichthyosis; Birt-Hogg-Dubé. Several of these are skin signs of tumour predisposition syndromes, which links this part to Part 11.

Part 4: Endocrinology (Chapters 21–28)

Disorders of sexual development and differentiation; Congenital adrenal hyperplasia; Androgen insensitivity syndrome; Klinefelter syndrome; Turner syndrome; Diabetes mellitus; Diabetes insipidus; Fabry–Anderson disease.

Part 5: Metabolic (Chapters 29–34)

An introduction to the genetics of metabolic disorders, followed by overviews of disorders of amino acid, carbohydrate and lipid metabolism, peroxisomal disorders, and disorders of purine and pyrimidine metabolism. Unlike most parts, these chapters are surveys of disease groups rather than single conditions.

Part 6: Gastroenterology (Chapters 35–39)

Inflammatory bowel disease; Wilson disease; Hereditary haemochromatosis; Coeliac disease; Pancreatic cancer.

Part 7: Haematology (Chapters 40–41)

Malignant haematology and Non-malignant haematology, two broad chapters that cover the whole field.

Part 8: Immunology (Chapters 42–58)

The largest part, with seventeen chapters on inborn errors of immunity: Severe combined immunodeficiency; Common variable immunodeficiency; Congenital abnormalities affecting development of the thymus; DNA repair defects; X-linked and autosomal recessive agammaglobulinaemia; Wiskott-Aldrich syndrome; Hyper-immunoglobulin M syndromes; Hyper-immunoglobulin E syndrome; Chronic mucocutaneous candidiasis; disorders of immune dysregulation and autoimmunity; familial haemophagocytic lymphohistiocytosis; Mendelian susceptibility to mycobacterial disease; Chronic granulomatous disease; Defects in leukocyte migration; Defects of toll-like receptors and their signalling pathways; Autoinflammatory diseases and periodic fever syndromes; Complement deficiencies.

Part 9: Neurology (Chapters 59–65)

Spinal muscular atrophy; Motor neurone disease/Amyotrophic lateral sclerosis; Fragile X syndrome; Huntington's disease; Dementia; Parkinson's disease; Myotonic dystrophy.

Part 10: Paediatrics and Obstetrics (Chapters 66–71)

Foetal anomaly screening; Prenatal diagnostic testing and preimplantation genetic diagnosis; Edwards' syndrome; Patau syndrome (trisomy 13); Williams syndrome; DiGeorge syndrome. The part combines reproductive testing with four chromosomal and microdeletion syndromes.

Part 11: Oncology (Chapters 72–81)

Introduction to cancer; Neurofibromatosis; Urological cancers; Peutz-Jeghers syndrome; Von Hippel-Lindau syndrome; Inherited bowel cancers; Inherited upper gastrointestinal cancers; Inherited breast cancer; Retinoblastoma; Multiple endocrine neoplasia. Chapter 1 already uses neurofibromatosis type 2 and multiple endocrine neoplasia type 1 as examples of diagnosis from a cluster of signs.

Parts 12–14: Ophthalmology, Renal, Musculoskeletal (Chapters 82–99)

Ophthalmology: Congenital and childhood cataracts; Colour blindness and achromatopsia; Retinitis pigmentosa; Primary congenital glaucoma; Bardet–Biedl syndrome. Renal: Polycystic kidney disease; Nephronophthisis; Medullary cystic kidney disease; Alport syndrome; Cystinosis; Cystinuria. Musculoskeletal: Marfan syndrome; Ehlers-Danlos syndrome; Congenital limb deficiencies; Duchenne muscular dystrophy; Charcot–Marie–Tooth; Ankylosing spondylitis; Skeletal dysplasias.

Key Concepts

Part 1: Introduction

• Clinical genetics versus genomic medicine: diagnosing and managing families with mainly single-gene and chromosomal conditions, versus integrating genomic, clinical and other data to predict and personalise care.
• Pedigree: the standard family-tree drawing used to identify who is at risk and to suggest an inheritance pattern.
• Variant interpretation: deciding whether a genetic change found by testing is relevant to a patient's condition or risk.
• Pharmacogenetics: predicting drug metabolism, side effects or lack of effect from variants in drug-handling genes.
• Genetic test report and counselling: reading a laboratory result and explaining risk to patients and families, each with its own chapter.

Parts 2–14: Conditions by system

• Cancer predisposition syndromes: inherited conditions such as neurofibromatosis, Von Hippel-Lindau syndrome and multiple endocrine neoplasia, spread across the dermatology and oncology parts.
• Inborn errors of immunity: the seventeen immunodeficiency and immune dysregulation conditions of Part 8.
• Inborn errors of metabolism: grouped by the pathway affected in Part 5.
• Prenatal and preimplantation testing: the reproductive applications covered in Part 10.

Critical Analysis

Strengths

• Organised by system. Wiley describes a systems-based approach, and the contents bear it out: a student on a cardiology, dermatology or renal placement can go straight to the genetic conditions of that specialty.
• Practical introductory chapters. Part 1 includes a chapter on how to read a genetic test report and one on genetic and genomic counselling, tasks a junior doctor actually meets, alongside the basics of inheritance and laboratory techniques.
• Clinical breadth. More than ninety condition chapters reach rare disorders seldom given a heading in short books (Mal de Meleda, Birt-Hogg-Dubé, nephronophthisis), and the publisher presents the book as an on-ward reference as well as a study text.
• Current view of genomics. The sample chapter covers variant interpretation, genome-wide association studies, pharmacogenetics, circulating tumour DNA and the use of linked health data, placing single-gene genetics within genomic medicine.

Limitations

• Short introduction for a beginner. All of inheritance, cytogenetics and molecular techniques fit into Chapters 2–3, about six pages. Readers without a grounding in mechanisms of inheritance and genetic variation will need a principles-first book alongside it.
• Uneven weighting. Immunology has seventeen chapters, while haematology has two and common conditions such as diabetes, dementia and Parkinson's disease share the format with rare syndromes. The balance reflects the contributors' choices more than how often conditions are met.
• UK and NHS context. The sample chapter discusses NHS laboratory accreditation, UK insurance rules and the 100,000 Genomes Project; readers in other systems will need local guidance on testing and insurance.
• Multi-author unevenness. As an edited volume with many contributors, chapter structure varies (from one page to four), and the sample chapter mixes established practice with forward-looking views on artificial intelligence and consumer data, which students should read as opinion rather than settled practice.

Where It Fits in the Course

This is one of two short entry points to the medical genetics course. Read and Donnai's New Clinical Genetics is the other, a case-based introduction that starts each chapter from patients and families and builds the science as it goes, from inheritance and chromosomes to genomic testing, cancer genetics, pharmacogenetics and ethics. The two suit different needs: Read and Donnai teaches the principles through cases, while this book is a condition-by-condition reference organised by specialty. For a first course, start with Read and Donnai, or with the principles chapters of a textbook, and use this book to look up conditions met on placements.

Emery's Elements of Medical Genetics and Genomics and Thompson & Thompson Genetics and Genomics in Medicine are fuller textbooks that explain inheritance, genetic variation and testing in depth and should carry the scientific foundation. Harper's Practical Genetic Counselling is a specialist guide to risk estimation and counselling that extends Chapter 5, and Strachan and Read's Human Molecular Genetics is the advanced treatment of genome organisation and disease mechanisms.

How to Use This Book

The publisher addresses medical students and newly qualified practitioners, and presents the book both as an introduction and revision text and as a reference on the ward. Readers will get most from it with basic cell biology and an outline of DNA, chromosomes and Mendelian inheritance; Chapters 2–3 review these only briefly.

A practical plan:

• Read Part 1 in full first. Chapter 1 sets out what clinical genetics and genomic medicine involve; Chapters 2–3 are a compact review of inheritance and techniques; Chapters 4–5 on test reports and counselling apply to every later chapter.
• Then read by placement or lecture block. Read the part that matches the current specialty: cardiology during a cardiology attachment, Part 10 with obstetrics, Part 11 with oncology. Part 8 is best read when immunology is taught.
• Connect related chapters across parts. Tuberous sclerosis, Gorlin, Cowden and Birt-Hogg-Dubé syndromes (Part 3) belong with the cancer predisposition chapters in Part 11; Duchenne muscular dystrophy (Part 14) with spinal muscular atrophy and myotonic dystrophy (Part 9).
• Practise with test reports. After Chapter 4, return to it while reading condition chapters, and use the glossary for unfamiliar terms.
• Check local practice. For testing pathways, insurance and screening outside the UK, use national guidance.