CARDIOSKELETAL MYOPATHIES IN CHILDREN AND YOUNG ADULTS

Section I. Physiology and Molecular Basis of Muscle
• Chapter 1. Ventricular Systolic Function
Introduction
Heart Rate and the Bowditch Effect
Summary
• Chapter 2. Basics of Skeletal Muscle Function and Normal Physiology
Introduction
Development of Skeletal Muscle
Muscle Growth
Skeletal Muscle Architecture, Contractile Apparatus, and Fiber Types
The Basement Membrane and Muscle Fiber Plasma Membrane
The Neuromuscular and Myotendinous Junctions
• Chapter 3. Molecular Pathways in Cardiomyopathies
Cardiac Muscle Development
Skeletal Muscle Development
Neurohormonal Regulation in the Heart: ß-Adrenergic Receptors and the Renin-Angiotensin-Aldosterone System
Sarcomere and Cytoskeleton Organization in Cardiac Muscle
Metabolism/Metabolic Pathways in Cardiac Development
Autophagy in the Cardiovascular System
Apoptosis and Necrosis in the Heart
Epigenetic Regulation of Cardiac Development and Disease
• Chapter 4. Abnormal Muscle Pathology and Physiology
Introduction
The Muscular Dystrophies
Duchenne Muscular Dystrophy
Congenital Muscular Dystrophy
Limb-Girdle Muscular Dystrophy
Emery-Dreifuss Muscular Dystrophy
Myotonic Muscular Dystrophy
Spinal Muscular Atrophy
Mitochondrial Myopathy
Friedreich Ataxia
Animal Models
Anatomy of Breathing in Muscular Dystrophy
Inspiratory Muscles in Muscular Dystrophy
Animal Models and Breathing Differences
Transgene Therapy
Cardiorespiratory Disease
Conclusion
Section II. Diseases of Cardio-Skeletal Phenotypes
• Chapter 5. Dilated Cardiomyopathy and Cardioskeletal Involvement
Definition
Epidemiology
Natural History
Etiology and Pathophysiology
Diagnosis
Management
Future Directions
• Chapter 6. Hypertrophic Cardiomyopathy
Introduction
Diagnosis and Etiology
Differential Diagnosis
Natural History and Prognosis
Management
Genetic Testing and Family Evaluation
Conclusions and Future Directions
• Chapter 7. Restrictive Cardiomyopathy Associated With Skeletal Myopathies
Introduction
Physiology of Diastole
Diagnostic Testing for Restrictive Cardiomyopathy
Pathophysiology of Restrictive Cardiomyopathy
Restrictive Cardiomyopathy in Patients With Skeletal Myopathy
Summary
• Chapter 8. Left Ventricular Noncompaction Cardiomyopathy
Introduction
Pathology of Left Ventricular Noncompaction
Incidence of Left Ventricular Noncompaction
Clinical Features and Diagnosis of Left Ventricular Noncompaction
Subtypes of Left Ventricular Noncompaction
Imaging of Left Ventricular Noncompaction
Electrocardiography in Left Ventricular Noncompaction
Arrhythmias in Left Ventricular Noncompaction
Clinical Genetics of Left Ventricular Noncompaction
Molecular Genetics of Left Ventricular Noncompaction
Animal Models of LVNC
Therapy and Outcome
Conclusions and Summary
• Chapter 9. Diseases of the Cytoskeleton: The Desminopathies
Introduction
Microfilaments
Microtubules
Desmin
Desmin Function
IF-Associated Cardiomyopathies: A Subgroup of Myofibrillar Myopathy
The Desmin-Related Cardiomyopathies
Animal Models: A Window into Cardiomyopathic Mechanisms
Desmin-Associated Proteins: Mechanistic Insights into the Disease
PAO Can Cause Heart Disease and Failure
Therapeutic Targets
• Chapter 10. Diseases of Cardiac Sarcomeres
Introduction
Sarcomere Function in Cardiac Filling and Ejection
Cardiac Sarcomeres as a Hub of Cellular Signaling
Sarcomere Control Mechanisms as Rate Limiting and Major Contributors to Cardiac Dynamics
Signaling Cascades in Diseases of the Sarcomere
Phosphorylation as a Modifier of Pathology due to Sarcomere Protein Mutations
TnI Phosphorylation and HCM
Redox and Nitrosative Signaling and Cardiac Sarcomeres
Therapies Preventing or Reversing Progression to Hypertrophy, Cardiac Dysfunction, and Sudden Death
Summary
• Chapter 11. Diseases of the Intercalated Disc
Introduction
The Role of Desmosomal Proteins in Cardioskeletal Myopathies
Pathology and Disease Mechanisms in Desmosomal Protein-Related Cardiomyopathies
The Role of Nondesmosomal Proteins in Cardioskeletal Myopathies
Clinical Diagnosis and Management of Cardioskeletal Myopathies
Genetic Testing in Cardioskeletal Myopathies
• Chapter 12. Diseases of the Nuclear Membrane
A Cellular Perspective
A Clinical Perspective
An Organismal Perspective
Section III. Metabolic Causes of Disease
• Chapter 13. Mitochondrial Disorders Causing Cardioskeletal Myopathies in Childhood
Introduction
Inheritance
Normal Cardiac Metabolism
Cardiomyopathy due to Mitochondrial Dysfunction
Cardiomyopathy due to mtDNA Mutations
Cardiomyopathy due to Mutations in Nuclear DNA
Mitochondrial Fatty Acid Beta Oxidation Defects
• Chapter 14. Nonmitochondrial Metabolic Cardioskeletal Myopathies
Introduction
Inborn Errors of Metabolism Associated With Cardiomyopathy and/or Skeletal Muscle Disease Classified by Disorder Group
Laboratory Studies for Confirmation of IEMs
Conclusion
Section IV. Syndromal and Chromosomal Causes of Disease
• Chapter 15. Cardio-Skeletal Muscle Disease Associated With Syndromes
Introduction
Cardiac Physiology and Metabolism
Cardiovascular Disorders of Mitochondrial Function
Fabry Disease
Danon Disease
Adenosine Monophosphate–Activated Protein Kinase Deficiency
Congenital Disorders of Glycosylation
Chromosomal Syndromes Associated With Cardiomyopathy
Trisomy 21 (Down Syndrome)
1p36 Deletion Syndrome
Chromosome 8p23.1 Deletion
Turner Syndrome
Other Chromosomal Disorders Associated With Cardiomyopathy
RASopathies: Disorders of the RAS-MAPK Signaling Pathway
Noonan Syndrome With Multiple Lentigines
Neurofibromatosis and NF1
Coffin–Lowry Syndrome
Pierre-Robin Sequence
Sotos Syndrome
Marfan Syndrome
Ehlers-Danlos Syndromes
Septo-Optic Dysplasia
Alström Syndrome
Conclusions
• Chapter 16. Cardioskeletal Muscle Disease Associated With Chromosomal Disorders
Congenital Heart Disease and Chromosomal Disorders
CHD and the Microdeletion/Microduplication Syndromes
Conclusion and Future Direction
Section V. Cardio-Skeletal Myopathies Associated With Congenital Heart Disease
• Chapter 17. Cardioskeletal Myopathies in Congenital Heart Diseases
Introduction
Exercise Limitation in Acquired Heart Failure
Peripheral Changes in Acquired Heart Failure
Systemic Changes in Heart Failure
Exercise Training in Acquired Heart Failure
Future Directions
Conclusions
Section VI. Future Directions in the Diagnosis and Management of Cardioskeletal Myopathic Disease in Children and Young Adults
• Chapter 18. Future Diagnostic Strategies—Pediatric
Introduction
Noninvasive Imaging
Electrophysiology: Advances in Fluoroscopic Radiation Reduction
Emerging Diagnostic Strategies in Cardiac Catheterization
Monitoring in the Cardiac ICU
Integration of Recent Genetic Findings Into Pediatric Cardiology Practice
Conclusions
• Chapter 19. Neuromodulation of the Failing Heart
Overview of the Cardiac Autonomic Nervous System
Sympathovagal Imbalance in Heart Failure
Assessment of Autonomic Nervous System Activity
Therapeutic Modulation of the Autonomic Nervous System in Heart Failure
Emerging Therapies for Neuromodulation of the Failing Heart
Future Directions
Overview and Conclusion

• Reveals the link between cardiac muscle disease and skeletal muscle disease
• Explains how genetics and environmental factors effect muscle function of diverse origins
• Designates current and novel therapeutic strategies that target both cardiac and skeletal muscle systems

Authors
• John Lynn Jefferies, Cincinnati Children’s Hospital, OH, USA;
• Burns Blaxall, Cincinnati Children’s Hospital, OH, USA;
• Jeffrey Towbin, Cincinnati Children’s Hospital, OH, USA
• Jeffrey Robbins, Cincinnati Children’s Hospital, OH, USA