A-Band 5, 59, 128 AAA Proteases 378 AC133+ Cells 32-33 ACADVL

Cambridge University Press 978-0-521-87629-2 - Disorders of Voluntary Muscle, Eighth Edition Edited by George Karpati, David Hilton-Jones, Kate Bushby and Robert C. Griggs Index More information

Index

A-band 5, 59, 128 Addison disease 472 amyotrophic lateral sclerosis atrophy, muscle 29 AAA proteases 378 adenine nucleotide translocase (ALS) 108 electron microscopy 143, 144 fiber-type specific 100–101 AC133þ cells 32–33 (ANT1) 380 Andersen disease, see brancher deficiency histopathology and ACADVL gene defects 404 adeno-associated virus (AAV) immunoanalysis 95, 99, 108 vectors 197 Andersen–Tawil syndrome neurogenic aging-related 500 acetazolamide 412, 419, 420–421 (ATS) 415, 416–417 adenosine triphosphate, see ATP – autophagic vacuolar myopathies acetazolamide-responsive diagnosis 417 418 adenovirus vectors 197 molecular basis 59, 416 adult onset 56 myotonia 412 drug-induced 478 adipose tissue, increased 95, 96 treatment 419 acetylcholine (ACh) 453 see also periodic paralysis infantile 56 adr mouse 410–411 X-linked congenital 56 acetylcholine receptors (AChR) anesthesia 453 adrenal myopathies 472 myasthenia gravis 481–482 autophagic vacuole proteins 55 – autoantibodies 48, 453 454 myasthenic complications 481 autophagic vacuoles with – adult polyglucosan body clustering 45 46, 52, 463 nondystrophic myotonias sarcolemmal features – disease 396 gene mutations 47, 463 464 412–413 (AVSFs) 56 inherited deficiency 47, 463–464 age of onset 183, 184 – past history 175 176 axial myopathy (camptocormia) localization 3, 4, 46 age-related motor-unit periodic paralyses 419 167–168 acetylcholinesterase (AChE) 4–5 remodeling 500 see also malignant – azathioprine 446–447, 457 endplate deficiency 461 463, aging 499–500 hyperthermia 467 impaired muscle regeneration 28 ANT1 mutations 380 B cells 439 inhibitors, mitochondrial changes 140 anti-Jo antibodies 437 B7 costimulatory molecules 439 see anticholinesterases neurogenic muscle atrophy 500 – – N-acetylmannosamine sarcopenia of 499–500 antibiotics 479, 481 482 B17.2L (NDUFA12L) 377 378 (ManNAc) 493, 495 satellite cells 30 anticholinesterases 457, 459, bacterial myositis 442 acid maltase, see a-glucosidase agrin 4–5, 52–53, 463 461, 501 barrier-to-autointegration factor AChR clustering 45–46, 52 congenital myasthenic (BAF) 64 acid phosphatase 101 mini-agrin 52, 53 syndromes 467 acquired myopathies 183, 191 neural and muscle isoforms diagnostic testing 457 Barth syndrome 380 – drug-induced myasthenia 481 – – acromegaly 473 52 53 basal lamina 4 5, 48, 142 143 anticipation, genetic 349–350 actin 59 alanine transaminase (ALT) 186 basophilia 96 accumulation 106–107, 118, 134 alcohol abuse 475, 478–480, 503 antimalarial drugs 478 Becker muscular dystrophy – – ACTA-1 mutations 60, 289 290 alcoholic myopathies 478–480, apoptosis 147, 214 (BMD) 205 206 g cytoplasmic - 62 503 carriers, see dystrophinopathy filamentous (F-actin) 3, 59, 128 arm levitation phenomenon 443 carriers filaments 3, 5 aldolase A deficiency 396 arthrogryposis, distal 60, diagnosis 215–220 – immunohistochemistry 103, Alpers–Huttenlocher syndrome 283–284, 290 genetic counseling 221 222 – – – 106 107 (AHS) 370, 371, 379 molecular basis 42 43, 206 213 myosin crosslinking 3, 59 arthrogryposis multiplex molecular testing 218–220 alpha motor neurons 1–2 congenita 455 actin aggregate myopathy 129, 290 MRI 152 amino acid metabolism 70 aspartate transaminase (AST) 186 muscle biopsy 215–217 alpha-actinin 3, 61 histo- and cytochemistry amiodarone 478 ataxia and epilepsy, autosomal – – acute quadriplegic myopathy recessive 371 109 110, 216 217, 218 (critical illness myopathy) ammonia 394 immunoblotting 107, 217 ATP, generation 67, 365, 390 – 130, 477 amphotericin B 478 light microscopy 101,108 111 ATP6 mutations 367 secondary protein defects 110 acyl-CoA dehydrogenase 9 amphyphysin-2 (BIN1) 55, 294 pathogenesis of myofiber (ACAD9) deficiency ATP12 mutations 377 – amyloid myopathy 147, 503 damage 213 215 397, 399, 405 ATPase 97–98, 116 see also dystrophinopathies

507

© in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-0-521-87629-2 - Disorders of Voluntary Muscle, Eighth Edition Edited by George Karpati, David Hilton-Jones, Kate Bushby and Robert C. Griggs Index More information

Index

Becker myotonia 57, 409–410 gene (CACNA1S) mutations carnitine:acylcarnitine centronuclear myopathy, – bedside diagnosis 163 58, 415, 417 418 translocase (CACT) see myotubular/ neuromuscular junction 453 deficiency 69, 399, 405 centronuclear myopathies benign acute childhood myositis (BACM) 444 calcium release junctions, carnitine palmitoyl-transferase cerebellar atrophy, congenital see triads (CPT) 69, 402–403 muscular dystrophy beta (skeleto-fusimotor) motor with 276 neurons 1–2 calpain(s) 214, 240 carnitine palmitoyl-transferase I (CPT-I) deficiency 399, 405 channelopathies, see ion Bethlem myopathy (BM) calpain-3 (p94) 240 gene mutations 61, 239–240 clinical features 397, 402 channelopathies 268–269, 299–300, muscle biopsy 122 307–310 protein interactions 53, 327 CHAT, see choline clinical features 301, 308 calpainopathy (LGMD2A) carnitine palmitoyl-transferase II acetyltransferase diagnosis 309–310 239–241 (CPT-II) deficiency 399, chemokines 439 – 402–403 future perspectives 310 311 clinical features 239 children genetic counseling 310 diagnosis 240–241 clinical features 397, 403 muscle biopsy 122, 140, 402 inflammatory myopathies genotype–phenotype genotype–phenotype – – 444 445 correlations 308 309 correlations 240 carnitine transporter deficiency muscle examination 182–183 histopathology and immunoblotting 107, 240 (primary carnitine immunoanalysis 117, management 241 deficiency) 397, 402, chloride channels 57–58 270, 309 molecular basis 61, 239–240 406–407 ClC-1 splicing 351–352 management 310 MRI 152–153, 154 molecular basis 69, 399 gene (CLCN1) mutations 57–58, molecular basis 48–50, 307–308 pathology 107, 111, 240 muscle biopsy 122, 140, 141, 402 410–411 MRI 157, 158, 309 camptocormia 167–168 cataracts chloroquine-induced myopathy – 56, 136, 137, 478 bicycle exercise test 187 188, cancer, see malignant disease congenital muscular dystrophy 394, 395 with 276 cholesterol-lowering agent cap disease 60, 290 myotonic dystrophy 356 BIN1 gene mutations 55, 294 – myopathies (CLAM) 168, electron microscopy 129 130 476–477 biochemical basis of disease 37–72 histopathology and catch property 12, 13 – immunoanalysis 120, 288 cats, muscular dystrophy 43 choline acetyltransferase (CHAT) biochemical tests 186 187 gene mutations 46, 461, biopsy 94 capillaries caveolae 54 462, 465, 466, 467 depletion 124, 144, 146 enzyme assays 187 – caveolin-3 54, 211 chorionic villus samples 94 muscle, see muscle biopsy electron microscopy 144 145 dysferlin interaction 53, 334–335 pipe-stem 144, 443 CHRNE gene mutations 462, Bjornstad syndrome 377 gene mutations, carbenoxolone 478 see caveolinopathies 463–464, 465, 466 blood vessel-associated cells overexpression 54, 211 – carbohydrate metabolism 67, 68 CHRNG gene mutations 463 32 33, 199 – disorders of 391 396 caveolinopathies 54 chronic fatigue syndrome 168 blood vessels carbonic anhydrase inhibitors 419 distal phenotype 158, 237 electron microscopy 144–145 LGMD presentation 237 chronic progressive external see also capillaries carcinomatous myopathy 500–501 phenotypes 211, 237 ophthalmoplegia (CPEO) 368 bone marrow-derived cells 32 cardiac involvement, see heart CCTG repeats 350, 353 disease classification 189–193 bone marrow pancreas (Pearson) CCUG RNA repeats 353 age of onset 183, 184 syndrome 370 cardiolipin 364, 365 CD133þ/AC133þ cells 32–33 hereditary/acquired distinction botulism 86, 87 abnormalities 380 183, 191 cell therapy 30–33, 196 brain involvement, see central cardiomyopathic hamster predominant patterns of (CMH) 41 blood vessel-associated cells weakness 164–168 nervous system (CNS) 32–33, 199 involvement cardiomyopathy proposed system (Brooke) 190 markers to track donor cells 32 simple system 183, 193 brancher deficiency 137, 139, 396 cysteine-rich protein 3 (CSRP3) mutations 61 central core disease (CCD) 292 clinical assessment 163–189 branching enzyme 67 dystrophinopathies 205–206, malignant hyperthermia 289, 293 clofibrate 476 Brody disease 71, 171 220 – mitochondrial disorders 381 molecular basis 70 71, 292 Coat disease 318, 319 Brody syndrome 71 myofibrillary myopathies 490 MRI 156 muscle pathology 112, 119, coenzyme Q (CoQ) 365 BSC1L mutations 377 telethonin mutations 245 131, 132, 288 deficiency 380, 405 tropomyosin mutations 60 – cachexia 29, 500 oral supplements 381 382 X-linked dilated, see X-linked central nervous system (CNS) – calcium cardiomyopathy involvement 174 cofilin-2 60, 289 290 glycogen degradation 67 a carnitine -dystroglycanopathies 258, 260 colchicine 478 mediated damage in primary deficiency, examination 177 – dystrophinopathies 214 a cold-sensitive myotonia 411 412 see carnitine transporter laminin- 2 deficiency 263 collagen calcium channels, voltage-gated deficiency myotonic dystrophy 355 fibers 4–5 (VGCCs) 3, 56–57, 58 secondary deficiency 402 peripheral nerve immunohistochemistry 105 autoantibodies 48, 458 supplements 402, 406–407 hyperexcitability syndromes 460 overproduction, see fibrosis

508

Index

collagen vascular diseases, with short stature, mental inflammatory myopathies Danon disease 294 see connective tissue retardation and distal 445–446 molecular and biochemical disorders laxity 276 myasthenia gravis 457 basis 56 – collagen VI 48–50, 269–271, 303, type 1A (MDC1A), sarcoidosis 505 muscle biopsy 122, 135 136 a – 307–308 see laminin- 2 deficiency steroid myopathy 475 476 debrancher deficiency 395–396 gene defects 49, 50, 271–272, 307 type 1B (MDC1B) 276 costameres 62, 208–209 type 1C (MDC1C; FKRP- debrancher enzyme 67, 69 immunohistochemistry 105, – – costimulatory molecules 439 107, 115, 117, 270, 309 related) 246 247, 257 262 dendritic cells 439 type 1D (MDC1D; LARGE- COX, see cytochrome c oxidase – collagen-VI-related myopathies related) 39, 257–262, denervation 13 14 268–273, 307–310 258–259 COX6B1 mutation 377 electron microscopy 143, 144 clinical features 271, 301, 308 COX10 mutations 377 EMG features 83 – congenital myasthenic histopathology and diagnosis 269, 272, 309 310 – syndromes (CMS) 46 48, COX15 mutations 377 immunoanalysis 95, 108 genetic counseling 310 – – 460 468 satellite cell changes 29 genotype phenotype – coxsackieviruses 441 correlations 271–272, clinical features 460 461, cramp-fasciculation syndrome deoxyguanosine kinase 308–309 462, 466 – (C-F) 459–460 (DGUOK) 379 management 272–273, 310 diagnosis 465 467 – genetic counseling 467 dermatomyositis (DM) 427 molecular basis 48 50, – cramps 169 269–271, 307–308 genotype phenotype drug-induced 474 childhood 428, 433, 444 – transitional phenotypes 271 correlations 465 clinical features 427 428, 430 management 467 cranial nerve innervated muscles, diagnosis 431–435 see also Bethlem myopathy, – strengthassessment178–180 Ullrich congenital postsynaptic 460, 463 465 drug-induced 478 muscular dystrophy presynaptic 460, 461 creatine kinase (CK), serum 186 electron microscopy 134, 143, slow-channel, see slow-channel 144, 146, 147 creatine supplements 382 COLQ gene mutations 46, syndrome extramuscular features – 461 463, 465, 466 synaptic basal lamina- critical illness myopathy (CIM) 430–431 – complex repetitive discharges associated 460, 461 463 (acute quadriplegic immunopathogenesis 435–437 – (CRDs) 83 congenital myopathies 282–295 myopathy) 130, 477 malignant disease 430 431 MRI 159–160 compound muscle action classification 282, 283 Crohn disease 442 clinical features 282–284 muscle pathology 99, 100, potentials (CMAPs) 81, aB-crystallin 63 – – – diagnosis 284–285, 291 123 124, 431 435, 436 82, 85 87, 89 gene (CRYAB) mutations 486 differential diagnosis 285, 289 sine myositis 428 computed tomography (CT) genetic counseling 289 aB-crystallinopathy 63 skin rash 175, 176, 428 – 151, 188 genotype–phenotype clinical features 484–485 treatment 445 447 congenital fiber type disproportion correlations 284, 287 muscle imaging 489 dermomyotome 20 imaging 156–157, 285 muscle pathology 486 (CFTD) 288, 292 desmin 3–4, 63 management 285–289 actin mutations 60 CTG repeats 348–350 mutations 486 molecular basis 282, 283 histopathology and satellite cells 23 immunoanalysis 116, 120 muscle biopsy 118–120, 285 CUG-binding protein 1 selenoprotein-1 mutations 71 with no known genes (CUGBP1) 66, 352 desminopathies 63, 331–332 tropomyosin mutations 60 284, 294 CUG RNA repeats 350–352 clinical features 484 with unusual structures 120 muscle imaging 159, 489 congenital inflammatory Cushing syndrome/disease 472 muscle pathology 486 myopathy 445 connective tissue disorders – 504–505 cycle ergometry 187 188, 394, 395 developmentally regulated congenital muscular dystrophies inflammatory myopathies 442 cyclophilin D 214 proteins 102–103 (CMD) 257–276 muscle pathology 124, 144 with adducted thumbs 274 cyclophosphamide 446, 457 DGUOK mutations 379 connective tissue proliferation, a-dystroglycan glycosylation cyclosporin diabetes mellitus 473 and other membrane see fibrosis angiopathy 144, 146 – collagen VI-related disorders receptor defects 257 262 Conn syndrome 472 50, 270–271, 311 thigh muscle infarction with cataracts 276 188, 473 contractures 168–169, 170, inflammatory myopathies 446 with cerebellar atrophy 276 myasthenia gravis 457 classification 257 171, 299 diagnosis extracellular matrix protein collagen VI-related cysteine-rich protein 3 (CSRP3) 61 bedside 163, 164 defects 114–115, 263–273 myopathies 308, 310 initial differential 183 – cytochrome c 365 histopathology and Emery Dreifuss muscular diagnostic testing 163, 164, dystrophy 305 cytochrome c oxidase (COX) – immunoanalysis 95, 105, – 183 189 107–108, 109, 113–116 – – fiber typing 96, 97 98 core myopathies 70 71, 292 293 3,4-diaminopyridine (DAP) with joint hyperlaxity, isolated deficiency 377 electron microscopy 131, 132 459, 467, 501 autosomal recessive 273 mitochondrial disorders 98, histopathology and 99, 122–123, 374 MRI 154 immunoanalysis 118–119 dichloroacetate 382 – nuclear protein defects 273 274 cytokines 439 dichlorphenamide 419 sarco/endoplasmic reticulum corticosteroid therapy – Duchenne muscular dystrophy cytoplasmic bodies 131, 133 2,4-dienoyl-CoA reductase protein defects 115 116, – 274–276 220 221 cytoskeleton, muscle fiber 3, 61–64 deficiency 397, 399, 405

509

Index

dietary management dominant diseases, molecular distal phenotype, see Miyoshi immunohistochemistry fatty acid oxidation defects therapies 200 myopathy 103–104 – – 403, 404, 406 407 dominant negative effects 200 genotype phenotype dystrophinopathies 101, mitochondrialdisorders381–382 correlations 335 109–110, 216, 217 periodic paralysis 418 dropped head syndrome 167–168 LGMD2B presentation 241–242 dystrophinopathy carriers differential diagnosis, initial 183 drug history 176 management 242, 335 101, 110, 217, 219 molecular basis 53, 242 females with Xp21 dimethylglycine 382 drug-induced myasthenic mouse models 53–54, 335 translocations 111 – – syndromes 479, 480 482 pathology 111, 112 secondary defects 104 diplopia 167, 455 456 clinical presentations 480–481 dysphagia 175 X-linked cardiomyopathy distal anterior compartment identification 481 111 – inflammatory myopathies 430 myopathy 53 management 481 482 isoforms 41–42, 207–208 mechanisms 481 oculopharyngeal muscular – distal arthrogryposis 60, dystrophy 341, 344 related proteins 44 45, 207 283–284, 290 drug-induced myopathies 473–482 structure 42, 207 dystrobrevin 43–44 distal hereditary motor autophagic 478 dystrophin-associated – – neuropathy 56 clinical syndromes 474 475 dystroglycan(s) 4 5, 40, 209 glycoprotein complex hypokalemic 478 complex 37–40 (DGC) 37–45, 210 distal myopathies 54, 323–337, 492 – inflammatory 428, 443 444, immunoblot analysis dystrophinopathies 209–211, adult onset dominant 478 107–108, 115 217 (MPD3) 337 – mitochondrial 477 478 immunohistochemistry 102, immunohistochemistry 104, 110 caveolinopathies 158, 237 painful 168, 169, 474 105, 109, 110, 115 transgenic mouse studies 212 classification 323, 324 painless 176, 475 laminin binding 42, 51 early adult dominant 337 dystrophinopathies 205–222 location of proteins involved drugs of addiction 475 a-dystroglycan 37, 247 animal models 43, 211 – 323, 325 Duchenne muscular dystrophy glycosylation 37 38, 40 diagnosis 215–220 MRI 157–159 (DMD) 205 glycosylation defects, electrodiagnostic testing 215 myopathies with distal animal models 43, 211 see a-dystroglycanopathies genetic counseling 221–222 phenotypes 325, 337 carriers, see dystrophinopathy b-dystroglycan 37, 247 history 205 with respiratory failure 337 carriers microscopy of muscle biopsies – – a-dystroglycanopathies 209, 108–111 type 1 (MPD1), see Laing cell therapy 30 31, 32 33, 221 – – – 246 249, 257 262 molecular background 206–213 myopathy cytogenetic analysis 217 218 – – animal models 39 40 molecular testing 218–220 vocal cord and pharyngeal diagnosis 215 220 – – clinical features 246 247, pathogenesis of myofiber (VCPDM; MPD2) 337 genetic counseling 221 222 – 259 261 damage 213–215 see also specific myopathies impaired muscle regeneration – diagnosis 248, 258 259, phenotypes 205–206 distal myopathy with rimmed 28, 215, 216 – 261 262 serum creatine kinase 215 vacuoles (DMRV; Nonaka mimics 206 – future therapies 40, 262 therapy 220–221 myopathy) 333–334 molecular basis 42 43, 54, – genetic counseling 262 see also Becker muscular molecular basis 56, 333–334, 492 206 213 – – genotype phenotype dystrophy; Duchenne pathology 137, 334 molecular testing 218 220 – molecular therapies 197–200, correlations 247 248, 261 muscular dystrophy distal myotilinopathy 159, 330–331 221 histopathology and immunoanalysis 115, dystrophinopathy carriers 206 distal nebulin myopathy 158, MRI 152, 153 genetic counseling 221–222 – 259, 261 290–291, 336 muscle biopsy 213, 215 217 immunohistochemistry 101, electron microscopy 143, LGMD2I presentation 245, distal neuromyopathy, dominant 246–249 110, 217, 219 147, 211 MRI 152 337 histo- and cytochemistry LGMD2K, 2M and 2N presentations 248–249 serum creatine kinase 215 distal pattern of weakness, 103–104, 109–110, 216–217 – – management 248, 262 ecsit 377 predominantly 164 166, 195 histology 95, 101, 108 111 – immunoblotting 217 molecular basis 38 40, 247, 259 distal upper/proximal lower edrophonium test 457, 481 light microscopy 216 dystrophia myotonica, extremity weakness 166, 195 secondary protein defects see myotonic dystrophy EFG1 mutations 378 disuse 13, 29, 500 – 110, 216 217 dystrophin 3, 41–43, 208–212 Ekbom syndrome 370 pathogenesis of myofiber diuretics 478 – deficient mouse, see mdx Elderly, see aging damage 213 215 mouse DMPK gene and protein 347, preimplantation diagnosis 222 electrical activity, adaptation 14 350–351 function 42, 209 prenatal diagnosis 94, 222 – electromyography (EMG) 82–85 – functional partners 39, 208 212 DNA mismatch repair proteins therapy 220 221 gene 41, 206–207 insertional and spontaneous 348 see also dystrophinopathies mRNA transcript activity 82–83 – docosahexaenoic acid 404, 406 DUX4 317 manipulations 198 macro 88 89 – motor unit morphology 84–85 dynamin-2 (DNM-2) 55, 293 mutations 42 43, 191, 209, dogs, muscular dystrophy 43, 211 212–213 motor unit recruitment 85, 86 – – – Dok-7 45–46, 464 dysferlin 53 54, 242, 334 335 promoters 41–42, 207–208 needle 82 83 – replacement therapy quantitative 89 DOK7 gene mutations 47–48, dysferlinopathies 241 242 – 197–198, 212 single-fiber (SFEMG) 87–88 462, 464–465, 466 clinical features 241 242, 335 diagnosis 242, 334, 335 immunoblotting 107, 217 electron microscopy 128–148

510

Index

electron transferring flavoprotein episodic ataxia type I (EA-I) family history 176–177 gene mutations 38–40, 247, (ETF) 69, 405 419–421 257–258, 260–261 fascicles, muscle 5 – electron transferring Escobar syndrome 47, 463 genotype phenotype fast-channel syndrome 47, 463 correlations 247–248, 261 flavoprotein:ubiquinone etanercept 457 oxidoreductase (ETF:QO) fatigue 171, 181 Fukuyama type congenital – 69, 405 ethanol abuse 475, 478 480, 503 fatigue index 9 muscular dystrophy gene (ETFDH) mutations 405 – (FCMD) 257–262 examination, physical 177 183 fatty acid b-oxidation defects – – clinical features 259–260 electrophysiological tests 81 91, children 182 183 69, 396–407 – diagnosis 258–259 185 186 inspection and palpation clinical features 397, 401, 403 – – genotype–phenotype disease signatures 89 91 177 178 genetic counseling and muscle 177–183 correlations 261 emerin (EMD) 64, 65–66, 300, 303 prenatal diagnosis 406 neurological 177 investigations 391, 405–406 functional tests, bedside gene mutations 65, 302, 305 – – percussion 181 management 406–407 180 181 immunodetection 116 117, 306 reflex testing 181–182 null mouse 66 molecular genetics 399 fusimotor (gamma) motor strength assessment 178–181 – – muscle biopsy 122, 140 141, neurons 1–2 Emery Dreifuss muscular exercise 402, 405–406 dystrophy (EDMD) adaptation to 12–13 pathophysiology 396–401 gastrointestinal involvement 299, 300–307 175, 356 energy sources 67, 390 fatty acid metabolism 67–69, autosomal dominant (AD induced pain 168, 169 gastroparesis 356 EDMD; EDMD2) 390, 401 – intolerance GCN triplet repeats 341–342, 343 65 66, 300 fatty acid oxidation defects fetus autosomal recessive (AR 396–401, 406 akinesia 47, 273 GDF8, see myostatin EDMD; EDMD3) 300, 305 glycogenoses 392–395 muscle biopsy 94 clinical features 300, 305 gene periodic paralysis 418 FHL1 (SLIM1) 61, 294 mRNA transcript, therapeutic diagnosis 306 therapy 357, 381 future perspectives 310–311 manipulation 198 fibrates 476 – genetic counseling 306–307 exercise testing 89, 90, 187–188, replacement therapy 197 198 fibrillation potentials 82–83 genotype–phenotype 394, 395 translational interference 198 – correlations 305 306 exon skipping approach 198 fibroblast growth factors (FGFs) gene defects management 306 26–27 direct therapeutic correction – experimental autoimmune molecular basis 300 305 fibroblasts, cultured 94 198 mouse models 66 myasthenia gravis phenotypic heterogeneity 191 MRI 155 (EAMG) 454, 481 fibrosis 28 types 189 muscle biopsy 116–117, – electron microscopy 145–147 extracellular matrix (ECM) 4 5 gene therapies, see molecular 133–134, 306 – light microscopy 95, 96, 105 electron microscopy 145 147 therapies X-linked (XL EDMD; protein defects 263–273 therapeutic interventions – EDMD1) 65–66, 300 protein immunohistochemistry 199 200 genetic diagnosis, molecular 93, 188–189 EMG, see electromyography 105 filamentous inclusions regulation of satellite cells intranuclear, see intranuclear germanium 478 end-plate potential (EPP) 453 25, 26 inclusions glucose endocrine myopathies 175, tubular, see tubulofilaments eye problems 174 as energy source 67, 390 471–473 facioscapulohumeral filamin C 63 intravenous, fatty acid endomysium 4–5 dystrophy 319 gene mutations 486–489 oxidation defects 406 myotonic dystrophy 356 – filaminopathy 63, 485 metabolism 67, 68, 390 energy metabolism 67 70, 390 symptoms 166–167, 175 muscle imaging 489 enlargement, muscle 171–172, 173 see also ocular muscle a-glucosidase (acid maltase) 395 deficiency, see Pompe disease – weakness FKRP, see fukutin-related protein b-enolase deficiency 394 395 X-linked vacuolar myopathy flesh-eating disease 442 enzyme assays 187 F-actin, see actin, filamentous with normal, see Danon – fluoxetine 463, 467 disease enzyme histochemistry 97–99, 101 facial weakness 178 179 force of muscle contraction, glutaric aciduria type II (GAII), eosinophilia–myalgia syndrome facioscapulohumeral muscular dystrophy (FSHD) 314–319 control 11–12, 13 see multiple acyl-CoA 428, 443, 478 – dehydrogenase deficiency clinical features 314 315, 316 force–time curves 12 eosinophilic fasciitis 443 diagnosis 317, 318 glycogen forearm exercise test 187, 394 eosinophilic polymyositis 443 genetic counseling 319 electron microscopy 137 – genotype phenotype FRG1 317 granules (glycosomes) eosinophilic syndromes 443 correlations 317–318 – fukutin 38–40, 258 4, 66 67 ephedrine 467 histopathology 117, 317 – histology 97 management 316, 318–319 gene mutations 249, 257 258, epidermolysis bullosa simplex metabolism 67, 68, 69 molecular DNA testing 260 and muscular dystrophy – 316–317, 318 genotype phenotype glycogen storage disease 0 137, 396 (EBS-MD) 63 correlations 261 molecular genetics and glycogen synthase 67, 396 epilepsy and ataxia, autosomal pathogenesis 316–317 fukutin-related protein glycogenin 67 recessive 371 MRI 155–156 (FKRP) 247

511

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glycogenoses 391–396 graft-versus-host reaction 444 human T cell lymphotropic virus immunosuppressive therapy associated with weakness (HTLV-I) 441 inflammatory myopathies 446 – granulomatous myopathy 433, 395 396 442, 504–505 Huntington disease (HD) 200 myasthenic disorders 457, 459 electron microscopy 137 inclusion body myopathies, with exercise-induced growth, muscle 29 Hutchinson–Gilford progeria – syndrome (HGPS) 66 hereditary, see hereditary symptoms 392 395 growth factors (GFs) 26–27 inclusion body myopathies histopathology and hyaline body myopathy 60 immunoanalysis 121–122 growth hormone deficiency 473 inclusion body myositis (IBM; molecular and biochemical hearing impairment 318, 381 hydroxychloroquine 478 sporadic inclusion body basis 67, 68 myositis; s-IBM) 427 heart disease 172–173, 174 hyperactivity states, muscle type II, see Pompe disease – clinical features 427–428, Andersen–Tawil syndrome 169 171 type IV, see brancher 429–430 416–417 hyperaldosteronism, primary 472 deficiency diagnosis 431 Emery–Dreifuss muscular type VII, hyperbaric oxygen 28 electron microscopy 133, 134, dystrophy 305 see phosphofructokinase 136–137, 138, 143, 144, fatty acid oxidation defects 401 hypercalcemia 502 (PFK) deficiency 145, 434 inflammatory myopathies 430 type VIII, hyperCKemia 54, 186, 237 extramuscular features 430–431 limb-girdle muscular see phosphoglycerate familial inflammatory 429 dystrophies 235–236, hyperkalemic periodic paralysis kinase (PGK) deficiency immunopathogenesis 437–441 238, 244 (HyperPP) 58, 416 type IX, see phosphoglycerate MHC-I expression 434 myotonic dystrophy 355–356, see also periodic paralysis kinase (PGK) deficiency MRI 159–160 356–357 – type X, see phosphoglycerate hyperparathyroidism 472 473, muscle pathology 99, 106, see also cardiomyopathy – mutase (PGAM) 501 502 123–124, 431–435 – deficiency hematoxylin and eosin (H&E) 94 hyperpolarized after-potentials treatment 445 447 type XI, see lactate heparin sulfate (HS) (AHPs) 10 infantile polymyositis with sick dehydrogenase (LDH) – proteoglycans 25, 26, 414 hypersensitivity vasculitis 442 myonuclei 444 445 deficiency hepatocyte growth factor (HGF) 27 hypersomnolence 355, 357 inflammatory cells glycolysis 67, 68 electron microscopy 143, 144 hereditary inclusion body disorders of 121, 137 hyperthyroid myopathy 471 light microscopy 99, 102, 124 myopathies (HIBM) – hypertrophy, muscle 29, 95, glycosyltransferases 37 38 429–430, 492–496 inflammatory myopathies (IM) 171–172, 499 GNE, see UDP-N- myosin mutations 60 427–447 disorders causing 172 acetylglucosamine 2 other conditions 496 children 444–445 fiber-type specific 100–101 epimerase/N- with Paget disease and clinical features 427–431 therapeutic induction 199 acetylmannosamine kinase frontotemporal dementia collagen vascular diseases 442 – (IBMPFD) 347, 430, 496 hypocalcemia 473, 502 combined mitochondrial GNE gene mutations 333 334, myopathy 444 quadriceps sparing, see GNE- hypokalemic myopathies, 492, 493 congenital 445 related hereditary drug-induced 478 GNE-related hereditary inclusion inclusion body myopathy diagnosis 184, 431–435 body myopathy (HIBM) hypokalemic periodic paralysis drug-induced 428, 443–444, 478 hereditary myopathies 183, 191 (quadriceps-sparing (HypoPP) 58, 415–416 electron microscopy 143, 144 classification 189–191 myopathy) 430, 492–496 see also periodic paralysis EMG findings 431 genotypic heterogeneity 190–191 animal model 494 etiology and pathogenesis phenotypic heterogeneity 191 hypoparathyroidism 473, 501–502 clinical features 429, 494 435–441 diagnosis 492, 493, 495 HIBM, see hereditary inclusion hypopituitarism 473 extramuscular features 430–431 distal myopathy with rimmed body myopathies hypothyroid myopathy 471 idiopathic (IIM) 427 – vacuoles and 333 334, 492 histochemistry 94–102 localized forms 443 genetic counseling 495–496 I-band 5, 59, 128 MHC-I expression 106, 434 – genotype–phenotype histology 94 102 imaging, diagnostic 151–160, 188 MRI 159–160 – correlation 494 495 histopathology 93–124 see also magnetic resonance muscle-derived serum – imaging 158 159, 334 – imaging enzymes 431 molecular basis 56, 333–334, history 163 177 muscle pathology 99, 123–124, – immobilization 500 492, 493 family 176 177 431–435 – past medical 175–176 see also disuse pathogenesis 493 494, 496 – with pipe-stem capillaries 443 pathology 123, 334, 493, 495 presenting complaint 163 172 immunoanalysis 93–124 secondary 427 social 177 treatment 495 – immunoblot analysis 100, 107–108 serum autoantibodies 437 systemic symptoms 172 175 statin-induced 476 goats, myotonic 410–411 – HIV-associated myositis 441 immunohistochemistry 102 107 treatment 445–447 Golden Retriever Muscular developmentally regulated see also dermatomyositis, HLA-G 438 – Dystrophy (GRMD) proteins 102 103 inclusion body myositis, dog 43, 211 HLA haplotypes, inclusion body primary protein defects polymyositis 103–104 Golgi apparatus 66–67 myositis 429 secondary protein defects inherited myopathies, Gömöri trichrome 94 Hoffman syndrome 471 104–107 see hereditary myopathies GRACILE syndrome 377 HSPG2 gene mutations 414 immunological synapses 439 injections, intramuscular 474

512

Index

injury, muscle 27–28 electrophysiological studies LGMD, see limb-girdle muscular limb-girdle pattern of weakness – innervation ratios 6–7 86 87, 459, 501 dystrophies 164, 165, 195 non-paraneoplastic (NP-LEMS) insulin-like growth factor-1 licorice (liquorice) 478 limb muscles, strength 458, 459 assessment 180–181 (IGF-1) 27, 503 paraneoplastic (P-LEMS) lid-lag sign 409, 411 insulin receptor (IR) 352 458, 459 limb-girdle muscular dystrophies limbic encephalitis (LE) 460 – – – integrin-a7-deficiency 45, 115, lamin(s) 64 65, 300 302, 303 (LGMD) 230 250 limit dextrin 67, 69 autosomal dominant (AD) 262 lamin A/C mutations – linker of nucleoskeleton and – 111, 230, 234 239 cytoskeleton complex integrin-a7b1 45, 51, 211, 262 (laminopathies) 65 66 autosomal recessive (AR) early onset phenotype – – (LINC) 64 integrins 4–5, 45 – 111 113, 230, 239 249 273 274 – lipid-lowering agent myopathies – classification 230 232 intellectual impairment 174, 318 Emery Dreifuss muscular diagnosis 232–234, 250 168, 476–477 dystrophy 302–303, intensive care unit (ICU) future therapies 250 see also statin myopathy 305–306 patients 477 genetic counseling 234 lipid metabolism 67–69 immunohistochemistry histopathology and interdigitated muscles 5 116–117 disorders, see fatty acid – immunoanalysis 98, b-oxidation defects interferon-a/b 436–437 LGMD1B 235 237 111–113 mouse models 66 management 232–234 lipid storage myopathy 401, 402, interferon-induced myopathy 478 – phenotypic heterogeneity 191, molecular basis 230–232 405 406 – intermediate filaments 3–4, 61–62 235, 305 MRI 152–154 electron microscopy 140 141 – intramuscular injections 474 lamina densa 142 143 prevalence 232 lipofuscin 134 see also basal lamina type 1A (LGMD1A) 63, 111, intranuclear inclusions (INI) – lipomatosis 175, 176 – lamina lucida 142–143 234 235 341 342, 343 type 1B (LGMD1B) 65, 66, lithium 478 laminin(s) 4–5, 51 – intranuclear rod myopathy 291 111, 235 237 liver 173–174 dystroglycan binding 42, 51 type 1C (LGMD1C) 54, intravenous immunoglobulin immunohistochemistry 111, 237 lobulated fibers 98, 99 (IVIg) 446–447, 457, 105–106, 114–115 type 1D (LGMD1D) 111, 238 459, 495 long-chain acyl-CoA structure 52 type 1E (LGMD1E) 111, 238 dehydrogenase (LCAD) 69 – ion channelopathies 57 59, 185, laminin-a2 deficiency (MDC1A) type 1F (LGMD1F) 111, 238 deficiency 397, 405 409–421 – type 1G (LGMD1G) 111, 263 268 long-chain L-3-hydroxyacyl- – 238–239 ion channels 3, 4, 56 59 clinical features 263, 264 CoA dehydrogenase diagnosis 263, 264–265 type 2A (LGMD2A), Isaac syndrome (acquired (LCHAD) deficiency genotype–phenotype see calpainopathy neuromyotonia) 420, 397, 399, 404, 406 correlations 264 type 2B (LGMD2B) 53, 111, 459–460 – management 265 112, 241 242 long QT syndrome 7 (LQT7) jitter 87–88 mini-agrin overexpression see also dysferlinopathies 416–417 type 2C–2F, 52, 53 low-density lipoprotein receptor- joint hyperlaxity, autosomal – see sarcoglycanopathies molecular basis 50 52, 263 related protein 4 45–46 recessive congenital – type 2G (LGMD2G; muscular dystrophy mouse models 51 52 muscle biopsy 103–104, telethoninopathy) 112, low energy laser irradiation with 273 – 105–106, 114–115, 264–265 244 246, 247 (LELI) 28 – KAL-1 protein 436 muscle hypertrophy with type 2H (LGMD2H) 60 61, LRPPRC mutations 377 secondary (MDC1B) 276 112, 246, 294 Kearns Sayre syndrome (KSS) 368 Luft disease 363 prenatal diagnosis 115, 265 type 2I (LGMD2I) 245, kidneys 175 246–248, 260–261 lung disease, inflammatory laminopathies, see lamin A/C King–Denborough syndrome 58 molecular basis 39, 247 myopathies 430, 437 mutations MRI 153, 154 – – lysosomal-associated membrane- Kocher Debre Semelaigne LAMP-2 56, 294 pathology 100, 102, 2 protein, see LAMP-2 syndrome 471 Deficiency, see Danon disease 112–113 laboratory investigations 183–189 gene mutations 56 see also lysosomal diseases 55, 134–137 a-dystroglycanopathies LAP2 64 M-bands 3, 5, 59 lactate 373, 394 type 2J (LGMD2J) 61, 113, lactate dehydrogenase (LDH) LAP2a mutations 65 249, 327 M-cadherin 22 – deficiency 394 395 – type 2K (LGMD2K) 113, M-CAM (CD56) 22 LARGE 38 40, 249 – Laing myopathy 332–333 gene mutations 257–258 248 249 type 2L (LGMD2L) 113, 249 macrophages 102 clinical features 332 Largemyd mouse 258, 262 imaging 158, 333 type 2M (LGMD2M) macrophagic myofasciitis 143, molecular basis 60, 332 laxatives 478 113, 249 145, 443, 478 type 2N (LGMD2N) 249 pathology 130, 333 Leber hereditary optic neuropathy magnetic resonance imaging (MRI) – – Lambert–Eaton myasthenic (LHON) 370, 381 limb-girdle myasthenic 151 152, 152 160, 188 syndrome (LEMS) 48, syndrome (LG-CMS) Leigh syndrome (LS) 370, 373 DOK7 gene mutations 465 magnetic resonance spectroscopy 458–459, 501 (MRS) 152, 188, 395 LEM domain family proteins 64 with tubular aggregates 465

513

Index

major histocompatibility menadione-linked electron microscopy 137–140, molecular therapies 196–200 complex, see MHC a-glycerophosphate 374 definitions 196 malignant disease dehydrogenase 101 epidemiology 364 dominant diseases 200 histopathology 98–99, 121, indications 196 cachexia 500 mental retardation, – – – carcinomatous myopathy see intellectual impairment 122 123, 373 374 recessive diseases 197 200 – imaging 159, 373 types 196 500 501 merosin deficiency, see laminin- dermatomyositis 430–431 late-onset myopathy 140 Morvan syndrome 460 – a2 deficiency management 380–382 Lambert Eaton myasthenic – mosaicism, facioscapulohumeral syndrome 458, 459, 501 MERRF (myoclonic epilepsy molecular diagnosis 375 380 mtDNA defects 363, 372, muscular dystrophy muscle wasting disorders with ragged-red fibers) 370 – – 375–376, 380–381 317 318 500 501 mesangioblasts 32–33, 199 peripheral nerve myopathic features 368 motor nerve conduction studies 81 – hyperexcitability metabolic myopathies 120 123, nuclear-genetic 363, 372, – – motor neurons 1–2 syndromes 460 390 407 376 380, 381 clinical presentations 390, 391 prenatal diagnosis 381 axons 2 malignant hyperthermia (MH) diagnostic testing 184–185, respiratory chain biochemistry firing rates and patterns 12 475 374–375 motor unit type-related 187, 390, 391 – periodic paralysis and 419 see also respiratory chain differences 10 11 MRI 159 – risk factors 58, 289, 293, 475 disorders synaptic specializations 10 11 RYR1 mutations 70 metalloproteinases 439 types 1–2 mitochondrial DNA (mtDNA) susceptibility testing 475 methotrexate 446, 505 – 69, 365–368 motor unit(s) 1 14 Mallory body-like inclusions 275 methylprednisolone 445 depletion syndromes 379–380 age-related remodeling 500 anatomy 1–6 Mallory body myopathy 71, 294 mexiletine 419 heteroplasmy and threshold expression 366 control of muscle force – MAN1 64 MHC class I (MHC-I) mitotic segregation 368 11 12, 13 – immunostaining 100, 106, 434 multiple deletion syndromes EMG morphology 84 85 ManNAc (N-acetylmannosamine) – 493, 495 upregulation 440, 438 380 FF 9, 10, 11 12 mutations 70, 363, 372, F(int) or FI 9 O-mannosyl glycosylation, microbial myositis, nonviral 442 – 375–376, 380–381 FR 9, 10, 11 12 disorders of, – – – microcephaly cortical dysplasia replication 366 functional organization 6 11 see a-dystroglycanopathies – peripheral neuropathy 276 secondary abnormalities 363 human muscles 9 10 – manual muscle testing 180 microtubules 61 structure, genetic code and innervation ratios 6 7 recruitment 11–12, 85, 86 – organization 365–366 Marinesco Sjögren syndrome mighty gene 26 S 9, 10, 11–12 (MSS) 134, 503–504 transcription 366 miniature end-plate potential translation 367 topographical territories 6 – masseter weakness 178 (MEPP) 453 transmission 367–368 types 8 9 functional correlates 10 McArdle disease minicores 284, 286 mitochondrial encephalopathy, motor neurons and synaptic (myophosphorylase misery, dermatomyositis 428 lactic acidosis and stroke- specializations 10–11 deficiency; glycogenosis V) like episodes (MELAS) – – – plasticity 12 14 392 mitochondria 4, 66 67, 137 138, 370, 373 diagnosis 394–395 364–365 motor unit potentials (MUP) molecular therapies 198 aging changes 140 mitochondrial 84–85 neurogastrointestinal muscle pathology 118, 119, biogenesis 365 mounding-phenomenon 181 121, 137, 394 electron microscopy 137–140 encephalopathy syndrome electron transport–oxidative (MNGIE) 370 mouse models mdm mouse 61 – phosphorylation system mitochondrial recessive ataxia dysferlin deficiency 53 54, 335 – mdx mouse 43, 211 69, 365 syndrome (MIRAS) 371 dystroglycanopathies 39 40 caveolin-3 overexpression 54 fatty acid b-oxidation 390, 401 dystrophinopathies 43, 211 mitochondrial trifunctional transgene studies 212 genetics 365–368 hereditary inclusion body protein (MTP) deficiency secondary abnormalities myopathy 494 medium-chain 3-ketoacyl-CoA 69, 397, 399, 404 363–364 laminin-a-2 deficiency thiolase (MCKAT) – structure and morphology mixed rod–core myopathies 288, (MDC1A) 51 52 deficiency 397, 399, 405 – 364–365 291–292 myotonia congenita 410 411 medium-chain acyl-CoA – myotonic dystrophy 66 dehydrogenase (MCAD) 69 mitochondrial disorders 69 70, Miyoshi myopathy (MM) (distal – – – myotubular myopathy 54 55 deficiency 396, 397, 399, 405 363 382 dysferlinopathy) 334 336 sarcoglycanopathies 41 abbreviations 364 clinical features 335 titin deletions 61 medium-chain triglycerides classification 363 diagnosis 334, 335 – (MCT) 406 407 clinical investigations 371–375 imaging 157, 158, 335 MPV17 mutations 379 MELAS (mitochondrial clinical presentation/ molecular basis 53, 242, MRC muscle strength scale 180 – encephalopathy, lactic syndromes 368–371 334 335 Mrf4 22 acidosis and stroke-like CNS and eye symptoms 174 pathology 112, 335 episodes) 370, 373 combined inflammatory molecular basis of disease 37–72 MrpL32 378 myopathy 444 MRPS16 and MRPS22 membrane trafficking and repair drug-induced 477–478 molecular genetic diagnosis proteins 53–56 93, 188–189 mutations 378

514

Index

MSH2 and MSH3 mismatch pathology specific to 100–101 differential diagnosis 417 pathology 106, 121, 123, repair proteins 348 plasticity 12–14 drug-induced aggravation 485–486, 487 predominance 108 479, 481 treatment and prevention multi-minicore disease (MmD) – 292–293 type 1 (SO) 7, 12 drug-induced unmasking 489 490 – a molecular basis 70–71, 292–293 type 2 7 8 479, 481 see also B- crystallinopathy, type 2A (FOG) 7–8 electrophysiological studies desminopathies, MRI 156 – – muscle biopsy 131, 132, type 2B 8 86 87, 88, 456 457 ZASPopathy 286, 292 type 2C 8 experimental autoimmune myofibrils 3 (EAMG) 454, 481 multiple acyl-CoA muscle LIM proteins (MLP) 61 annular 131, 132 with MuSK antibodies electron microscopy 128–131 dehydrogenase deficiency muscle nerves 1 (MuSK-MG) 454–455, 456 (MADD) 397, 399, 405 muscle RING finger proteins neonatal 455 myogenesis – molecular and biochemical (MURFs) 61 ocular , 455 456 aging muscle 30 basis 69 pathogenesis 453–455 embryonic development 20–22 riboflavin-responsive muscle-specific kinase, seronegative (SNMG) 455 factors regulating 25–27 (RR-MADD) 141, 405, see MuSK treatment 457, 458 genetic regulation 22, 23 406–407 – muscle regeneration 27–28 muscle tension 5 6 mycophenolate mofetil 446, 457 muscle(s) passive contributions 5–6 myogenic precursor cells 20–33 – Myf5 22, 23, 24 – anatomy 5 6 muscle unit 1 cell therapy 30 33 architecture 5 MYH7 gene mutations 60, 294, origin during development development 20–21 muscle wasting, see wasting, 332–333 20–21 – muscle examination 177 183 MYHC2A gene mutations 60 see also myoblasts, satellite interdigitated 5 muscleblind-like protein 1 cells myoadenylate deaminase pinnate 5 (MBNL1) 66, 352, 353 myogenic regulatory factors working lengths 5–6 (MAD) 101 muscleblind-like proteins deficiency 122 (MRFs) 22 muscle ankyrin repeat proteins (MBNL) 351, 352 myogenin 22 (MARPs) 61 myoblast transfer therapy muscular dystrophies (MTT) 30–33 myoglobin 7 muscle biopsy 93–94, 188 cell therapy 30–31, 32–33 – enzyme assays 187 classification 192, 193 myoblasts 20, 21 myoglobinuria 172, 173, 396 401 – fetal 94 diagnostic testing 184 conversion of non-myogenic drug-induced 474 475 – methods 93–94 early childhood onset, cells into 31 32 management 406 selection of site 93 see congenital muscular markers 23 muscle histology after 402, 406 tissue preparation 94 dystrophies plasticity 25 paroxysmal 403 regenerating muscle 28 muscle contraction 3, 59 histopathology and myokymia 420 immunoanalysis 108–118 source in adult muscle – – see also rippling, muscle muscle enlargement 171 172, 173 MRI 152–156 21 22, 31 myophosphorylase (muscle muscle eye brain disease (MEB) with proximal weakness, myoclonic epilepsy with ragged – see limb-girdle muscular phosphorylase) 67, 69 257 262 red fibers (MERRF) 370 deficiency, see McArdle disease clinical features 260 dystrophies – – – see also specific dystrophies myoclonus dystonia syndrome gene (PYGM) mutations 392 diagnosis 258 259, 261 262 243 histochemistry 101, 119, 121 molecular basis 39, 258 MuSK (muscle-specific kinase) MyoD 22, 23, 500 myosin muscle fiber(s) 45–46, 47–48, 463 – autoantibodies 48, 454–455, 456 myodystrophy mouse actin crosslinking 3, 59 anatomy 3 4 filaments 3, 5, 59, 128 arrangement in muscles 5 gene mutations 465 (Largemyd) 258, 262 – immunohistochemistry basement membrane 48 53 mutations, see gene defects myoedema 181 – – – 99 100, 102 103, 106 cytoskeleton 3, 61 64 neonatal 100, 102–103, 106 denervation and reinnervation MxA protein 436 myoferlin 53 13–14 myalgia, see pain, muscle myofibers, see muscle fiber(s) myosin heavy chain (MHC) 128 density 88 I 7 myalgia cruris epidemica 444 myofibrillary myopathies (MFM) differentiation 21 IIA 7–8 62, 484–490 distribution in motor units 6–7 myasthenia IIB 8 clinical phenotypes 484–485 shape variations 95 congenital, see congenital IIX (IID) 8 diagnosis 484, 485–489 size variation 95 myasthenic syndromes adaptation to exercise 12–13 electron microscopy 130–131, splitting 95, 98 drug-induced 479, 480–482 gene mutations, see MYH7 486, 488, 489 – prenatal 463 gene mutations; MYHC2A muscle fiber types 7 8 filaminopathy subset 63, 485 gene mutations myasthenia gravis (MG) 48, energy metabolism 67 genetic counseling 490 hybrid muscle fibers 8 453–457 – functional correlates 10 genotype phenotype isoforms 7 grouping 101, 108 with AChR antibodies correlations 484 hybrid 8 (AChR-MG) 453–454 imaging 159, 489 myosin-related myopathies identification 96, 97–98, avoidance of drug LGMD1A overlap 234–235 60, 120, 130 – – 99 100, 106 complications 481 482 mutation analysis 486–489 myosin storage myopathy – motor unit type associations clinical features 455 456 myotilinopathy subset 63, 60, 288, 294 – – 8 9 diagnosis 456 457 330, 485 electron microscopy 130, 131

515

Index

myositis molecular pathogenesis necrotizing fasciitis 443 neuropathy, ataxia and retinitis – benign acute childhood 66, 348 353 necrotizing fascio-myositis, pigmentosa (NARP) 370 (BACM) 444 multisystem involvement hyperacute 442 neurophysiological tests, nonviral microbial 442 355–356 Nelson’s syndrome 472 see electrophysiological viral infections 441 muscle histopathology 117, 355 tests see also inflammatory skeletal muscle involvement nemaline bodies (rods) 60, 118, – myopathies 354 355 284, 286, 289 nicotinamide adenine dinucleotide dehydrogenase myostatin (MSTN) 26, 500 time course 353 treatment 356–357 nemaline myopathy (NM) 285, tetrazolium reductase therapeutic inhibition 199 – type 1 (DM1) 347, 353 289 290, 336 (NADH-TR) 96, 97–98, – myotilin 63 animal models 66, 351 electron microscopy 128 129, 122–123 – 134 gene mutations 330 331, 486 instability of CTG repeats nicotinic acid 476 – histopathology and myotilinopathy 348 350 molecular therapies 200 immunoanalysis 110, nitric oxide synthetase, neuronal distal 159, 330–331 – RNA-mediated disease 118, 289 (nNOS) 43 44, 104, LGMD1A 234–235 – 350–352 molecular basis 60, 284, 210 211 muscle imaging 489 – type 2 (DM2) 347, 353 289 290 muscle pathology 487 – NKX2-5 352 instability of CCTG MRI 156 157 myofibrillary myopathy 63, – non-thyroidal hypermetabolism repeats 350 related disorders 290 292 330, 485 363 spheroid body myopathy RNA-mediated disease 353 neonatal myasthenia gravis 294, 330 type 3 (DM3) 347 (NMG) 455 Nonaka myopathy, see distal myopathy with rimmed myotubes 20, 21, 28 myotonia(s) 171, 409 neostigmine 481 vacuoles acetazolamide-responsive 412 myotubular/centronuclear – nerve conduction studies 81 82 Notch signaling 22, 24, 30 cold-sensitive 411–412 myopathies (MTM/CNM) nesprin-associated congenital drug-induced 475 54–55, 293–294 nuclear envelope 64–66, 303 EMG features 83, 195 – muscular dystrophy 274 animal models 54 55 nucleus (nuclei) examination 181 – autosomal 293 294 nesprins 64, 274 central 96, 133, 284, 286, 293 exercise testing 89 – dominant 55, 293 294 nestin 23 electron microscopy 132–134 grip 181, 182, 195 electron microscopy 133 internal 95–96, 133 myotonia congenita 409 neurogenic disorders histopathology and proteins 66 myotonic dystrophy 355, 357 immunoanalysis 114, electron microscopy 143, 144 non-dystrophic 409–413 119–120, 288, 293 histopathology and Numb 22, 24 – anesthesia risks 412 413 recessive 55, 294 immunoanalysis 108 nutritional myopathy 501–503 diagnosis 410, 413 X-linked 293 – neuroleptic malignant syndrome obscurin (and obscurin-like paradoxical 171, 411 412 – 475 percussion 83, 181, 182, 195 myotubularin 54 55, 293 protein) 61 periodic paralysis with 416 NDUFA1 mutations 376 neurological examination 177 ocular disorders, see eye problems potassium-aggravated 58, NDUFA11 mutations 376 neuromuscular junction (NMJ) – 412, 416 – ocular muscle weakness 166 167, 45 48, 453 195 sodium channel 412, 413 NDUFA12L (B17.2L) mutations anatomy 2–3, 4–5, 46 377–378 assessment 178 myotonia congenita 409–411, 413 autoimmune diseases 48 – see also ophthalmoplegia, autosomal dominant NDUFAF1 mutations 377 formation 45 46 ptosis – ion channels 3, 4 (Thomsen) 57, 409 410 NDUFS1–8 mutations 376 autosomal recessive (Becker) postsynaptic defects 47–48 oculopharyngeal muscular – 57, 409–410 NDUFV1 2 mutations 376 postsynaptic membrane 46, 453 dystrophy (OPMD) 341–344 exercise testing 89 nebulin (NEB) 59, 60 presynaptic defects 46, 47 diagnosis 341, 343 molecular basis 57–58, 410–411 mutations 60, 336 synaptic defects 46, 47 genetic counseling 344 sodium channel mutations distal myopathy 158, neuromuscular transmission genotype–phenotype 410, 412 290–291, 336 – 46 47, 453 correlations 342–343 nemaline myopathy 289–290 – myotonia fluctuans 412 autoimmune diseases 453 460 management 344 see also distal nebulin – disorders 453 468 molecular basis 341–342, 343 myotonia levior 410 myopathy, nemaline drug-induced disorders pathology 117–118, 133, 134, myopathy – myotonia permanens 412 480 482 342, 343 inherited disorders, myotonic dystrophy (DM) neck extensor myopathy, isolated see congenital myasthenic Oil red O 94–95 347–358 (INEM) 167–168 – syndromes ophthalmoplegia 167, 178 anticipation 349 350 neck extensor weakness 167–168, myotubular/centronuclear clinical features 353, 354 179–180, 195 neuromyotonia 48 congenital 349–350, 353 acquired (Isaac’s syndrome) myopathies 293 – diagnosis 347–348 neck flexor weakness 179 180 420, 459–460 progressive external, exercise testing 89 necrosis 27–28 clinical features 171 see progressive external future perspectives 357–358 electron microscopy 147–148 episodic ataxia type I and ophthalmoplegia – genetic counseling 357 histological features 96 419 421 oral foliate cells 94 genetic heterogeneity 347 inflammatory myopathies 124 familial isolated 420 osteomalacia 473, 501–502

516

Index

oxidative phosphorylation muscle histopathology 418 infantile, with sick myonuclei genotype–phenotype (OXPHOS) 138, 365, 390 neurophysiological tests 89, 444–445 correlations 261 see also respiratory chain 90, 418 localized 443 immunohistochemistry 115 disorders thyrotoxic (TPP) 417, 419, 472 MHC-I expression 434 – – protein O-mannosyl transferase 1 oxidative stress 214 treatment 418 419 MRI 159 160 (POMT1) 38–40 muscle pathology 123–124, – p94, see calpain-3 peripheral nerve hyperexcitability – gene mutations 249, 257 258 (PNH) syndromes, 431 435, 436, 437 genotype–phenotype PABPN1, see polyadenylation – nonviral microbial 442 acquired 459 460 – correlations 261 binding protein nuclear 1 treatment 445 447 peripheral nervous system tropical 442 protein O-mannosyl transferase 2 PABPN1 gene defects 341–342, 343 diseases involving 174 (POMT2) 38–40 Pompe disease (acid maltase – pain, muscle (myalgia) 168 examination 177 gene mutations 249, 257 258 deficiency) 56, 395 – diffuse 168, 169 symptoms 174 genotype phenotype MRI 159 correlations 261 drug-induced 474 perlecan 52, 414 muscle pathology 120, 121–122, exercise-induced 168, 169 – phenytoin 444 135, 137, 395 proteoglycans 4 5, 25, 26 focal and localized 168 see also agrin, perlecan strength assessment and 180 phosphofructokinase (PFK) post-tetanic potentiation (PTP) see also pain deficiency (Tarui disease) 12, 13 proximal myotonic dystrophy 101, 121, 394–395 (PDM), see myotonic paired helical filaments (PHFs), postoperative respiratory dystrophy (DM), type 2 see tubulofilaments phosphoglycerate kinase (PGK) depression 479, 481 deficiency 393, 394–395 proximal myotonic myopathy palatal weakness 179 postural myopathy, X-linked 61 (PROMM), see myotonic palpation, muscle 177–178 phosphoglycerate mutase potassium-aggravated myotonia dystrophy (DM), type 2 (PGAM) deficiency 58, 412, 416 – paramyotonia congenita (PC) 393–394, 394–395 pseudohypertrophy 171 172 411–412, 413, 416 potassium channelopathies 59 phosphorus magnetic resonance – pseudouridine synthase 1 (PUS1) exercise testing 89, 412 KCNA1 mutations 419 421 378–379 molecular basis 58, 412 spectroscopy 188, 395 KCNJ2 mutations 415, 416, 417–418 PTC124 198 paraneoplastic syndromes phosphorylase, muscle, – see myophosphorylase potassium channels, voltage-gated ptosis 166–167, 178, 455 500 501 – see also malignant disease phosphorylase b kinase (PHK) 67 (VGKCs) 420, 453 myasthenia gravis 455 456 – autoantibodies 48, 460 oculopharyngeal muscular paraplegin 378 deficiency 393, 394 395 – dystrophy 341, 344 physical examination, potassium chloride 418 419 parasitic polymyositis 442 purine nucleotide metabolism, see examination, physical potassium-depleting drugs 478 pathology 93–124 disorders of 122 pinnate muscles 5 prayer sign 48–49 – Pax3 22, 23 PUS1 mutations 378 379 pipe-stem capillaries 144, 443 prednisone 445–446, 457 Pax7 22, 23, 24, 30 pyomyositis 442 pituitary disorders 473 prenatal diagnosis 94 Pearson syndrome (PS) 370 pyridostigmine 457, 459, 461 plasma membrane 142–143 prenatal myasthenia 463 penetrance, variable 191 pyruvate 67 plasmapheresis (plasma presynaptic defects 46 D-penicillamine 444, 478 exchange) 446, 457, 459 quadriceps-sparing myopathy, procainamide 444 see GNE-related hereditary pentazocine-induced myopathy plasmid gene vectors 197 inclusion body myopathy 443 progression, rate of 183 plectin 63 quinidine sulfate 463, 467 PEO1, see Twinkle helicase progressive external POLG disease (POLG mutations) ophthalmoplegia (PEO) ragged red fibers (RRF) percussion, muscle 181 379, 380 autosomal dominant 371, 380 electron microscopy 138, 139 – perhexiline 478 clinical syndromes 370 371 autosomal recessive 371 histochemistry 96, 121, chronic 368 122–123, 374 periarteritis nodosa 442 POLG (POLG1) gene 363, 366 prostigmine 457, 461 RAPSN gene mutations 47, 462, pericytes 32–33 polyadenylation binding protein nuclear 1 (PABPN1) 464, 465, 466 – protein aggregation myopathies 61 periodic acid Schiff (PAS) 94 95,97 341–342, 343 – protein defects rapsyn 45 46, 464 periodic paralysis (PP) 414–419 polymerase g (POLG) 366 classification based on 190 recessive diseases, molecular anesthesia and 419 primary 103–104 therapies 197–200 differential diagnosis 417 polymyositis (PM) 427 – secondary 104–107 examination and laboratory childhood 444 445 recruitment of motor units 11–12 – upregulation of functional tests 417 clinical features 427 428, early 85, 86 – analog 198–199 genetic testing 417–418 428 429 EMG features 85, 86 – hyperkalemic (HyperPP) diagnosis 431 435 protein O-mannose beta-1, reduced 85 58, 416 drug-induced 478 2-N-acetylglucosaminyl- size principle 11 electron microscopy 143, 147 hypokalemic (HypoPP) transferase (POMGnT1) reducing bodies 101, 120 58, 415–416 eosinophilic 443 38–40 – molecular pathophysiology 418 extramuscular features 430 431 gene mutations 257–258 reducing body myopathy (RBM) immunopathogenesis 437–441 61, 294

517

Index

reflex testing 181–182 riboflavin supplements 405, ion channels 56–59 gene mutations 70, 71, 274–276 – 406–407 neuromuscular junction Mallory body myopathy 294 regeneration 27 28, 216 – electron microscopy 147–148 ribonucleotide reductase 45 48 multi-minicore disease trafficking and repair proteins 292–293 histopathology 96, 106 (RRM2B) 379 – – impaired 28 53 56 pathology 113, 115 116, ribosomes, free 66–67 transmembrane proteins 45 119, 275–276 therapeutic interventions – 28, 199 rickets 473 sarcomeres genotype phenotype transplanted muscle 28 proteins 59–61 correlations 275, 284 rigid spine muscular dystrophy 1 immunoblot analysis 116 see also necrosis (RSMD1) 71, 274–276 structure 3, 5, 59 reinnervation 13–14 clinical features 275 sarcopenia, age-related 499–500 sensory nerve action potentials (SNAPs) 81–82 histopathology and – renal failure immunoanalysis 115–116, sarcoplasm 66 70 acute 474–475 sensory nerve conduction studies 275–276 sarcoplasmic reticulum (SR) 81–82 chronic 175, 502 MRI 154, 155 3, 70–72, 141–142 serum biochemistry 186–187 repeated sequences, deletions rimmed vacuoles (RV) 135, sarcospan 41 or expansions 117–118 – Sherrington, Sir Charles 1 136 137, 138 sarcotubular myopathy 294 repetitive nerve stimulation inclusion body myositis 434 short-chain acyl-CoA (RNS) 85–87 oculopharyngeal muscular satellite cells 5, 21, 22–30 dehydrogenase (SCAD) 69 dystrophy 343 aging muscle 30 deficiency 397, 399, 405 respiratory chain 69, 365 atrophic muscle fibers 29 respiratory chain disorders rippling, muscle 181, 195, 420 blood vessel-associated cells short-chain L-3-hydroxyacyl-CoA 69–70, 372, 375–376 rippling muscle disease 54, 171, 237 and 32–33 dehydrogenase (SCHAD) deficiency 397, 405 assembly factor mutations rituximab 446, 457 dystrophinopathies 215 377–378 electron microscopy 22–24, short interfering RNAs biochemical diagnosis RNA splicing, abnormal 351–352, 147–148 (siRNAs) 352 374–375 353 factors regulating 25–27 – short stature, mental retardation, electron microscopy 139 140, rod–core myopathies, mixed genetic regulation 22, 23 distal laxity and congenital 141 288, 291–292 growing or hypertrophic muscular dystrophy 276 mitochondrial translation muscle 29 – defects 378–379 ryanodine receptors (RYR1) 70 71 markers 22–24 sialic acid 493–494, 495 gene mutations 70–71 mtDNA depletion syndromes plasticity 25 sialuria 493 379–380 central core disease 292 regenerating muscle 27–28 multiple enzyme defects 378 centronuclear myopathy 294 as source of myoblasts simple sequence repeats (SSRs) 348 multiple mtDNA deletion multi-minicore disease 292 21–22, 31 SIX5 gene 352 syndromes 380 pathology 112, 119 stem cell sub-population – SJL mouse 53–54 structural component defects localization 3, 56 57 24–25 – Sjögren’s syndrome 442, 504 376 377 sag property 9, 12 Sca-1 24 see also mitochondrial SANDO syndrome 371 skeletalmuscle,development20–22 disorders scapuloperoneal pattern of þ sarco/endoplasmic reticulum Ca2 weakness 166, 195 skeleto-fusimotor (beta) motor respiratory depression, ATPase1(SERCA1)71 neurons 1–2 postoperative 479, 481 scapuloperoneal syndrome þ sarco/endoplasmic reticulum Ca2 61, 496 skin respiratory failure 168 ATPase 2 (SERCA2) 71 (Stark–)Kaeser type 332, 484 biopsy 94 distal myopathy with 337 involvement 175 sarcoglycan–sarcospan complex scatter factor (SF; HGF) 27 respiratory function testing 181 – SLC22A5 gene mutations 402 39, 40 41 Schwartz–Jampel disease (SJD) respiratory muscles sarcoglycanopathies (LGMD 52, 413–414 sleep-related breathing disorders assessment 181 types 2C–2F) 242–244 357, 381 weakness 168, 195 scleroderma, see systemic sclerosis animal models 41 slow-channel syndrome (SCCMS) sclerotome 20 retroviruses 441 clinical features 243 47, 462, 463, 466, 467 – diagnosis 243–244 SCN4A mutations 58, 413, 465 revertant fibers 101, 109 110, small cell lung carcinoma genotype–phenotype myotonia congenita 410, 412 216, 217 (SCLC) 458, 460, 501 correlations 244 paramyotonia congenita 412 rhabdomyolysis management 244 periodic paralysis 415, 416, social history 177 amyloid myopathy 503 molecular basis 40–41, 243 – – 417 418 sodium channel myotonias drug-induced 474 475, 476 muscle biopsy analysis 107, sodium channel myotonias 412 412, 413 fatty acid b-oxidation defects 112, 216, 218, 243–244 – 396 401 SCO1 and SCO2 mutations 377 sodium channels 58, 413, 418 sarcoglycans 3, 40, 104–105, blockers 411, 412, 414 rheumatoid arthritis (RA) 124, 210, 243 SDHA mutations 376 gene mutations, see SCN4A 442, 504 second wind phenomenon 392, sarcoid myopathy 124, 442, mutations 394, 395 riboflavin-responsive multiple 504–505 voltage-gated (VGSC), acyl-CoA dehydrogenase selenoprotein 1 (SEPN1) 58, neuromuscular junction deficiency (RR-MADD) sarcolemma 3 – 71–72, 274–275 46, 453 141, 405, 406–407 electron microscopy 142 143

518

Index

somites 20 T cells tongue weakness 179 molecular basis 48–50, CD4þ 454 269–271, 307–308 b-spectrin 104 þ – total lymphoid irradiation cytotoxic CD8 437 438, (TLI) 446 MRI 154, 309 speech 179 438–439 muscle biopsy 107, 115, 269, spheroid body myopathy 63, transforming growth factor-beta 270, 272, 309 T regulatory (Treg) cells 454 b 294, 330 (TGF- ) superfamily 26 prenatal diagnosis 115, 310 T-system networks 142, 143 sphingolipids 25 translational interference 198 ultrasonography (US) 151, 188 T-tubules 3, 56–57, 141–142 spinal cord, motor neurons 1, 2 transplantation, muscle 28 ultrasound therapy 28 tacrolimus 446, 457 – spinal muscular atrophies (SMA) transverse (T) tubules 3, 56 57, ultrastructural studies – – 95, 101, 108 tafazzin 364 141 142 128 148 – spironolactone 418–419 target fibers 99, 108 trauma, muscle 27 28 UQCRB mutations 376 – spliceopathy 351–352, 353 Tarui disease, triads 3, 56 57 UQCRQ mutations 376 see phosphofructokinase triamterene 418–419 – Stark–Kaeser scapuloperoneal (PFK) deficiency urine tests 186 187 syndrome 332, 484 Trichinella myositis 433 – telethonin 60–61, 244 utrophin 44 45, 208 statin myopathy 168, 476–477 gene mutations 244, 245 TRIM32-related dystrophy extrasynaptic, in drugs increasing risk 477 – (LGMD2H) 60–61, 112, dystrophinopathies immunoanalysis 245 246 – hypothyroidism and 471 246, 294 216 217, 219 telethoninopathy (LGMD2G) immunohistochemistry – stem cells 24 25 112, 244–246, 247 triple repeat expansion 105, 110 bone marrow-derived 32 disorders 66 therapeutic upregulation 199 lineage conversion 31–32 temporalis muscles 178 myotonic dystrophy 347, therapy 30–33 tendon reflexes 181–182 348–353 vacuolar myopathies, autophagic, see autophagic vacuolar – oculopharyngeal muscular steroid myopathy 475 476 thick filaments 3, 59 – myopathies protein diseases 130 dystrophy 341 342, 343 steroid therapy, vacuoles see corticosteroid therapy proteins 128 tropomyosin (Tm) 3, 59, 128 gene mutations 60, 289–290 histopathology 102 stiff-person syndrome 171 thigh muscle infarction, diabetes rimmed, see rimmed vacuoles 188, 473 isoforms 60 stiffness 169–171 troponin 3, 59, 60, 128 vascular endothelial growth thin filaments 3, 59 factor (VEGF) 28 strength assessment 178–181 protein diseases 128–130 trunk muscles, strength cranial nerve innervated proteins 60, 128 assessment 180–181 vasolin-containing protein muscles 178–180 (VCP) 123 Thomsen myotonia 57, tubular aggregates 142, 465 limb and trunk muscles – VCP gene mutation 347 180–181 409 410 tubulofilaments 137, 138, MRC scale 180 thymectomy 457 433–434, 435 vectors, gene 197 respiratory muscles 181 thymic hyperplasia 454 Turner syndrome 206 very long-chain acyl-CoA dehydrogenase streptococcus, group A thymidine kinase-2 (TK2) 379 Twinkle helicase (PEO1) 366, beta-hemolytic 442 (VLCAD) 69 thymidine phosphorylase 379, 380 deficiency 397, 399, 402, 404, succinate dehydrogenase (SDH) (ECGF1) 380 ubiquinone, see coenzyme Q 405, 406 fiber typing 97–98 mitochondrial disorders 98, thymoma 442, 454, 457, 460 Udd myopathy, see tibial vincristine 478 – 99, 121, 122 123, 374 thyroid ophthalmopathy 472 muscular dystrophy viral infections, myositis 441 SUCLA1 and SUCLA2 mutations thyrotoxic periodic paralysis UDP-N-acetylglucosamine 2 viral vectors 197 380 (TPP) 417, 419, 472 epimerase/N- acetylmannosamine vitamin D deficiency myopathy – – Sudan black 94 95 tibial muscular dystrophy kinase (GNE) 333–334, 473, 501 502 – SUN proteins 64 (TMD) 326 328 492–494, 496 vitamin E deficiency myopathy clinical features 327 see also GNE gene mutations 502 SURF1 mutations 377 imaging 158, 327–328 swallowing, assessment 179 molecular basis 61, 326–327 Ullrich congenital muscular vocal cord and pharyngeal distal dystrophy (UCMD) myopathy (VCPDM; – synaptic defects 46 titin 3, 59, 60 61, 327 268–273, 299–300, MPD2) 337 – – synaptic specializations 10–11 associated proteins 60 61 307 310 deletions, mdm mouse 61 clinical features 269, 271, voltage-gated calcium channels, synaptogamin I, antibodies 459 mutations 61, 249, 293, 301, 308 see calcium channels, – voltage-gated syntrophins 3, 43–44 326 327 diagnosis 269, 272, 309–310 – – titin myopathy with future perspectives 310 311 Walker Warburg syndrome systemic lupus erythematosus – cardiomyopathy, genetic counseling 310 (WWS) 257 262 (SLE) 124, 442, 504 – congenital 61, 293 genotype phenotype clinical features 260 systemic sclerosis (SSc) 124, correlations 271–272, diagnosis 258–259, 261–262 442, 504 TK2 gene mutations 379 308–309 molecular basis 258, 261 – systemic symptoms 172–175 toluene 478 management 272 273, 310 (WWS)-like syndrome 39

519

Index

warm-up phenomenon 409 Welander distal myopathy X-linked vacuolar myopathy, ZASP 64, 107, 329 – wasting, muscle 171–172, 499 323 326 see Danon disease gene mutations 486 conditions causing 499–505 imaging 158, 326 Xp21 dystrophies, ZASPopathy 328–330 weakness 163–168 Western blotting, see dystrophinopathies clinical features 485 assessment, see strength see immunoblot analysis Xp21 translocations, females imaging 159, 329, 489 assessment Wnt, aging muscle 30 with 111, 206 pathology 330 – children 182 183 working lengths, muscle 5–6 Z-band alternatively spliced zebra body myopathy 292 give-way 180 X-linked cardiomyopathy 111, PDZ-motif containing zebrafish glycogenoses associated with protein, see ZASP RYR1 mutations 71 395–396 206, 212–213, 215 Z-band streaming 131, 133 selenoprotein 1 mutations inflammatory myopathies 427 X-linked myopathy with 71–72 myasthenic syndromes excessive autophagy Z-disks 3, 5, 59, 62, 128 455–456, 459 zidovudine-induced myopathy (XMEA) 56 pathology, myofibrillary – periodic paralyses 415 electron microscopy 136 myopathies 486, 488 441, 444, 477 478 predominant patterns histopathology and protein defects 62 ZNF9 gene 347, 353 – 164 168 immunoanalysis 122 proteins 59, 128

520