Neurogenetics for the Practitioner

1st Edition - April 24, 2024
Imprint: Academic Press
Editor: Gregory M. Pastores
Language: English
Paperback ISBN:
9 7 8 - 0 - 3 2 3 - 9 9 4 1 7 - 0
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 9 5 8 5 9 - 2

Neurogenetics for the Practitioner provides clinicians with a navigation tool to help diagnose and treat patients with neurological disorders using neurogenetics. Sections introd… Read more

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Neurogenetics for the Practitioner provides clinicians with a navigation tool to help diagnose and treat patients with neurological disorders using neurogenetics. Sections introduce the reader to an overview of genetic principles, including practical applications in relation to diagnosis and current limitations. Additional chapters highlight how to workup patients presenting with certain features, including cerebral palsy/intellectual disability, congenital muscular dystrophy, cognitive decline/dementia, peripheral neuropathy, and paroxysmal disorder. The final section explores therapeutic strategies based on genetic interventions and genetic counselling options. This internationally contributed book will become the essential reference guide for neurologists.

Cover image
Title page
Table of Contents
Copyright
Contributors
About the editor
Preface
Section A: General considerations
Chapter 1 Introduction
Abstract
Overview
Neurogenetics: A brief historical perspective
Current outlook and future prospects
Genes (and their products): Recent observations of interest
References
Chapter 2 Molecular genetic mechanisms of neurodevelopmental and neurodegenerative disease
Abstract
Introduction
Basic principles of Mendelian traits and inheritance
Molecular consequences of pathogenic variation
Modifiers of Mendelian inheritance patterns
Repeat expansion and anticipation
Non-Mendelian inheritance: Imprinting, mitochondrial inheritance, and uniparental disomy
Digenic or oligogenic inheritance
Multilocus pathogenic variation and blended phenotypes
Chromosomal disorders
Complex traits
Epigenetics
Conclusion
References
Chapter 3 Techniques for genetic diagnosis: A practical guide
Abstract
Introduction
Part I: Description of the main technologies
Part II: Variant interpretation
Conclusion
Glossary
References
Chapter 4 Genetic counseling and related issues
Abstract
Introduction
General process of genetic counseling and essential considerations
Related issues
References
Chapter 5 A complementary approach: Metabolomics
Abstract
Introduction
Tools of the trade
Applications
Conclusions and advice to the practitioner
References
Chapter 6 Genomics of psychiatric disorders
Abstract
Introduction
The complex genetic architectures of psychiatric disorders
GWAS
Rare variants
Looking beyond missense variants in autosomal genes
Cross-disorder genetic correlations
Moving from genetic data to biological function
Clinical relevance
Treatment implications of biological targets
Conclusion
References
Section B: Early-onset presentations
Chapter 7 Infant with hypotonia
Abstract
Introduction
Defining hypotonia
Physical examination of hypotonia
Central vs peripheral hypotonia
Diagnostic approach
Review of selected diagnoses
Conclusion
References
Chapter 8 Neurodevelopmental disorders
Abstract
Clinical vignette
Introduction
Genetic testing
Targeted therapies-illustrative cases
Conclusion
References
Chapter 9 Metabolic decompensation in an infant or child
Abstract
Clinical vignette
Introduction
Clinical presentation and relevant investigations
Management
Conclusion
References
Chapter 10 Neurocutaneous disorders
Abstract
Introduction
Case presentations
References
Section C: Later-onset presentations
Chapter 11 Metabolic decompensation in an adult
Abstract
Clinical vignette
Introduction
Clinical presentations and diagnosis
Management
Conclusions
References
Chapter 12 Stroke genetics
Abstract
Introduction
Inherited causes of stroke (Table 1)
Genetic counseling
Conclusion
References
Chapter 13 Dementia and cognitive decline
Abstract
Introduction
Epidemiology
Genetic dementias
Genetic counseling in dementia
Conclusion and future direction
References
Chapter 14 Muscle weakness (genetic muscle diseases)
Abstract
Case 1
Muscular dystrophies
Case 2: A condition that eludes next-generation sequencing
Case 3: A multisystemic disorder that was not identified by traditional genetic testing
Congenital myopathies
Congenital muscular dystrophies
Case 4: Congenital progressive weakness
Metabolic myopathy
Conclusion
References
Chapter 15 Episodic flaccid muscle weakness (Periodic paralysis)
Abstract
Key points
Indications the periodic paralysis may have an underlying genetic basis
Ancillary information that may be helpful to differentiate primary from secondary causes of periodic paralysis
Additional investigations that may be requested before or while awaiting the results of gene tests
Recommended genetic studies
Relevant genetic conditions
Treatment
Final considerations
References
Section D: Movement disorders
Chapter 16 Ataxia and spasticity
Abstract
Acknowledgments
Introduction
Clinical and genetic classifications
Representative HSP clinical syndromes
Particularly frequent genetic types of HSP
Differential diagnosis
Routine diagnostic evaluation
Diagnostic criteria
Neuropathology
Treatment
Prognosis
Future directions
References
Chapter 17 Involuntary movements and postures (Dystonia)
Abstract
Definition of dystonia
Classification of dystonia
Diagnostic evaluation
Management
References
Section E: Neuropathy and sensory problems
Chapter 18 Sensorimotor problem: Genetic neuropathies
Abstract
Introduction
Laboratory evaluation
Genetic neuropathies
Charcot-Marie Tooth diseases
Hereditary sensory and autonomic neuropathy
Familial amyloid polyneuropathy
Factors influencing phenotypic expression of neurologic diseases
Assignment of a gene defect
Conclusions
References
Chapter 19 Vision loss
Abstract
Case 1—Vision loss in an infant
Case 2—Vision loss in adulthood
Differential diagnoses of vision loss in childhood
Differential diagnoses of vision loss in adulthood
Inherited retinal disease
Ancillary testing and additional investigations
Genetic testing recommendations and factors that may increase likelihood of a positive result
Most common IRD genes, their mechanism(s) of disease, and phenotypes
Management, therapy, and clinical trials
Final considerations
References
Chapter 20 Hearing loss
Abstract
Introduction
Nonsyndromic hearing loss
Syndromic hearing loss
Mitochondrial disease can be syndromic or nonsyndromic
Genetic testing for hearing loss
Treatment and management approaches
Strategies for evaluation of hearing loss in patients with neurologic disease
References
Section F: Paroxysmal disorders
Chapter 21 Epilepsy
Abstract
Introduction
Practical considerations relating to testing in the neurology and medical genetics clinic
Conclusion
References
Chapter 22 Migraine
Abstract
Introduction
Monogenic migraine disorders
Hemiplegic migraine
Other monogenic migraine syndromes
Common types of migraine
When to perform genetic testing for migraine?
References
Section G: Organelle pathologies
Chapter 23 Neuronopathic lysosomal storage disorders
Abstract
Clinical vignette
Introduction
Conclusion
References
Chapter 24 Mitochondrial disorders: Nuclear-encoded gene defects
Abstract
Declaration of interests
Introduction to mitochondrial function
The complexity of mitochondrial disease genetics
A genetics first workflow to diagnose mitochondrial disease
Bioinformatic WGS/WES pipeline and variant filtration steps to detect SNVs and Indels
Detecting structural variations to supplement a genetics first approach
Challenges of variant interpretation
Additional omic technologies for diagnostic and functional testing of mitochondrial variants
Reproducing mitochondrial diseases using model organisms
Discussion
Concluding remarks
References
Chapter 25 Mitochondrial DNA-encoded defects
Abstract
Clinical vignette
Introduction
Clinical features
Diagnosis
Management
Conclusion
References
Section H: Neuroimaging findings as clues
Chapter 26 Brain malformations
Abstract
Acknowledgments
Anomalies of dorsal prosencephalon: Development anomalies of the cerebral commissures
Anomalies of Ventral Prosencephalon
Malformations of cortical development (MCD)
Anomalies of midbrain–hindbrain development
References
Chapter 27 Childhood-onset leukodystrophy
Abstract
Acknowledgment
Introduction
White matter, myelin, and brain myelination
The concept of leukodystrophy
Clinical aspects
Brain neuroimaging (see Table 5)
Insights on disease incidence and the results of genetic testing, as reported by certain centers
Therapies
Diagnostic algorithm for childhood-onset genetic leukodystrophies
Conclusions
References
Chapter 28 Adult-onset leukodystrophy
Abstract
Introduction
When to suspect a leukodystrophy
Radiological clues
Insights drawn from recent reports relating to genetic testing for genetic white matter disease
Selected leukodystrophies
References
Section I: Therapeutic considerations
Chapter 29 Pharmacogenetics
Abstract
Introduction
Pharmacogenetics (pharmacogenomics)
Next-generation sequencing and genomic medicine
Disorders of the brain and pharmacogenomics
ACH PGx test
Conclusion
References
Chapter 30 Therapeutic strategies based on genetic interventions
Abstract
Introduction
Challenges and limitations
Therapeutic strategies
Conclusions
References
Index

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

Health

Neurogenetics for the Practitioner

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Gregory M. Pastores

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