Cover -- Advisory Editors -- Title page -- Copyright page -- List of Contributors -- Preface -- List of Abbreviations -- 1: Introduction to Muscle Disease: Pathology and Genetics -- Introduction -- Structure of the book -- Conclusion -- Section 1: Assessment of Muscle Disease -- 2: Clinical Features of Muscle Disease -- Introduction -- Clinical history and examination -- Conclusion -- 3: General Pathology of Muscle Disease -- Introduction -- Selection of muscle to biopsy -- Biopsy technique -- Tissue preparation -- Use of other tissues for diagnosis -- Development of human muscle -- Histological and histochemical features of normal muscle -- Histological and histochemical defects in pathological muscle -- Structural abnormalities -- Absence of an enzyme -- Storage of a product -- Immunohistochemistry -- Electron microscopy -- Future perspectives -- 4: Genetics of Muscle Disease -- Introduction -- Discovery of genes causing muscle disease -- Benefits of finding the mutation causing a disease in a patient -- Types of DNA mutations -- Blurring of traditional clinical classifications - parallel nosologies -- Mutations within the same gene can cause a spectrum of phenotypes (as classified by classic nosology) -- One disease-related pathology can be caused by mutations in different genes -- Some genes are to date only implicated in one disease -- Some muscle proteins have not yet been associated with human disease -- Interesting recent developments -- The way forward, addressing the grand challenges in the genetics of muscle disease -- Conclusions and future perspectives -- Section 2: Neurogenic Muscle Disease -- 5: Neurogenic Muscle Pathology -- Defining denervation -- Clinical features -- Pathophysiology -- Pathological changes -- Fetal and infantile denervation -- Differential diagnosis -- Section 3: Diseases of Neuromuscular Transmission.

6: Autoimmune Myasthenias -- Introduction -- Incidence -- Clinical features -- Investigations -- Treatment and prognosis -- Pathology -- Genetics -- Differential diagnosis -- Animal models -- Lambert-Eaton myasthenic syndrome -- 7: Congenital Myasthenic Syndromes -- Introduction -- The neuromuscular junction -- Clinical features of congenital myasthenic syndromes -- Conclusions and future perspectives -- Section 4: Sarcolemma: Muscular Dystrophies and Related Disorders -- 8: Dystrophin and Its Associated Glycoprotein Complex -- Introduction -- Incidence -- Clinical features -- Pathology -- Genetics -- Animal models -- Conclusions and future perspectives -- 9: Proteins of the Extracellular Matrix -- Introduction -- Congenital muscular dystrophies -- Laminin α2 primary deficiency -- Collagen VI-related myopathies -- Perlecan-related disorders -- Laminin β2 and agrin-related disorders -- Animal models for extracellular matrix-related disorders -- Conclusions and future perspectives -- 10: Plasma Membrane Proteins: Dysferlin, Caveolin, PTRF/Cavin, Integrin α7, and Integrin α9 -- Introduction -- Dysferlin -- Caveolin-3 -- Polymerase I and transcript release factor/cavin-1 -- Integrin α7 and integrin α9 -- 11: Sarcolemmal Ion Channelopathies -- Introduction and classification -- Prevalence, genetics, and pathophysiology -- Clinical features -- Histopathology -- Magnetic resonance imaging -- Therapy -- Differential diagnosis -- Animal models -- Conclusions and future perspectives -- Section 5: Disorders of Nuclear Proteins and Nuclear Positioning -- 12: Proteins of the Nuclear Membrane and Matrix -- Introduction -- Clinical features -- Muscle pathology associated with defects in nuclear membrane proteins -- Genetics -- Animal models -- Conclusions and future perspectives -- 13: Centronuclear Myopathies -- Introduction.

Clinical, histopathological, immunocytochemical, and electron microscopy features -- Genetic bases of centronuclear myopathies -- Differential myopathological diagnosis -- Animal models -- Section 6: Early- and Late-Onset Disorders of Myofibrils -- 14: Thin Filament Proteins: Nemaline and Related Congenital Myopathies -- Introduction -- Sarcomeric thin filaments -- α-Skeletal actin (ACTA1) -- Tropomyosins -- Troponins (TNNT1, TNNT3, and TNNI2) -- Cofilin-2 (CFL2) -- Conclusions and future perspectives -- 15: Nebulin: Nemaline Myopathies and Associated Disorders -- Introduction -- Incidence -- Clinical features -- Pathology -- Genetics -- Differential myopathological diagnosis -- Animal models -- Conclusions and future perspectives -- 16: Myosins -- Introduction -- Autosomal dominant myosin heavy chain IIa myopathy, inclusion body myopathy 3 -- Autosomal recessive myosin heavy chain IIa myopathy -- Myosin storage myopathy -- Laing early-onset distal myopathy -- Scapuloperoneal and limb-girdle syndromes -- Distal arthrogryposis syndromes -- Animal models -- Conclusions and future perspectives -- 17: Disorders Caused by Mutant Z-disk Proteins -- Definitions of entities -- Clinical features -- Pathology -- Genetics and pathophysiology -- Differential myopathological diagnosis -- Future directions -- 18: Titin-related Distal Myopathies -- Introduction -- Epidemiology -- Clinical features -- Pathology -- Genetics -- Differential myopathological diagnosis -- Animal models -- Conclusions and future perspectives -- 19: Scapuloperoneal Disorders and Reducing Body Myopathy Associated with the Four and Half LIM Domain Protein 1 -- Introduction -- Scapuloperoneal disorders -- Reducing body myopathy -- Genetics of FHL1opathies -- Conclusion -- Section 7: Disorders Associated with Intermediate Filaments -- 20: Desminopathies -- Introduction.

Incidence, sex, age, and geographical distribution -- Clinical features -- Pathology -- Genetics -- Differential myopathological diagnosis -- Molecular pathogenesis and animal models -- Conclusions and future perspectives -- 21: Plectinopathies -- Introduction -- Incidence, sex, age, and geographical distribution -- Clinical features -- Pathology -- Genetics -- Molecular pathogenesis and animal models -- Conclusions and future perspectives -- Section 8: Mitochondria -- 22: Mitochondrial Myopathies -- Introduction -- Incidence and prevalence -- Clinical features -- Pathology -- Genetics -- Structural abnormalities of mitochondria in other disorders -- Animal models -- Conclusions and future perspectives -- Section 9: Sarcoplasmic Reticulum and T-tubules -- 23: Core Myopathies, Malignant Hyperthermia Susceptibility, and Brody Disease -- Introduction -- Incidence -- Clinical features -- Pathology -- Genetics -- Differential diagnosis -- Animal models -- Conclusions and future perspectives -- Section 10: Cytoplasmic Proteins -- 24: Enzymes: Cytosolic Proteins Calpain-3, SEPN1, and GNE -- Introduction -- Calpain-3 -- SEPN1 -- Pathology -- GNE -- 25: Proteins of Autophagy: LAMP-2, VMA21, VCP, and TRIM32 -- Introduction -- LAMP-2 and Danon disease -- Other myopathies with autophagic vacuoles with sarcolemmal features -- Inclusion body myopathy with Paget disease of bone and frontotemporal dementia, a neurodegenerative disease due to valosin-containing protein mutation -- Tripartite motif protein 32 mutations in limb-girdle muscular dystrophy 2H or sarcotubular myopathy -- Other relevant proteins implicated in autophagy -- Conclusion -- 26: Chaperone Proteins -- Introduction -- Incidence -- Clinical features -- Pathology -- Genetics -- Differential myopathological diagnosis -- Animal models -- Conclusions and future perspectives -- 27: Kelch Proteins.

Kelch protein myopathies -- Section 11: Metabolic and Storage Disorders -- 28: Disorders of Muscle Glycogen Metabolism -- Introduction -- Clinical overview -- Muscle pathology -- Overview of genetics and prevalence -- Glycogenoses with exercise-induced symptoms -- Glycogenoses associated with muscle weakness and atrophy -- 29: Disorders of Lipid Metabolism -- Introduction -- Carnitine palmitoyltransferase 2 deficiency -- Very long-chain acylcoenzyme A dehydrogenase deficiency -- Mitochondrial trifunctional protein deficiency -- Phosphatidic acid phosphatase (lipin) deficiency -- Primary carnitine deficiency -- Multiple acylcoenzyme A dehydrogenase deficiency -- Neutral lipid storage disease with ichthyosis or myopathy -- Conclusions and future perspectives -- Section 12: Muscle Diseases with DNA Expansions -- 30: Myotonic Dystrophies Type 1 and 2 -- Introduction -- Incidence -- Clinical features -- Histopathology of congenital and childhood myotonic dystrophies -- Histopathology and electron microscopy of myotonic dystrophy type 1 -- Histopathology and electron microscopy of myotonic dystrophy type 2 -- Genetics -- Differential clinical and pathological diagnosis -- Animal models -- Conclusions and future perspectives -- 31: Oculopharyngeal Muscular Dystrophy -- Definition of entities -- Molecular genetics and pathophysiology -- Structural changes -- Genotype-phenotype correlation -- Future perspectives -- Section 13: Facioscapulohumeral Dystrophy -- 32: Facioscapulohumeral Dystrophy -- Introduction -- Incidence, gender, age, and geographic distribution -- Clinical features -- Therapy -- Pathology -- Myopathological differential diagnosis -- Pathogenesis: genetics, epigenetics, transcriptional factors.

The current facioscapulohumeral muscular dystrophy pathogenesis model: genetic abnormalities permit epigenetic and transcriptional defects leading to facioscapulohumeral muscular dystrophy.