Disease and Inheritance Gene and Locus Clinical Findings Pathologic Findings

Central core diseases; autosomaldominant

Ryanodine receptor-1 (RYR1) gene;

19q13.1

Early-onset hypotonia and nonprogressive

weakness; associated skeletal deformities; may

develop malignant hyperthermia

Cytoplasmic cores are lightly eosinophilic and distinct

from surrounding sarcoplasm; Found only in type 1

fibers, which usually predominate, best seen on

NADH stain

Nemaline myopathy; autosomaldominant

or autosomal-recessive

Autosomal-dominant (NEM1)—

Tropomyosin 3 (TPM3) gene;

Autosomal-recessive (NEM2)—

nebulin (NEB) gene; 2q22

Weakness, hypotonia, and delayed motor

development in childhood; may also be seen in

adults; usually nonprogressive; involves

proximal limb muscles most severely; skeletal

abnormalities may be present

Aggregates of subsarcolemmal spindle-shaped

particles (nemaline rods); occur predominantly in type

1 fibers; derived from Z-band material (a-actinin) and

best seen on modified Gomori stain

Autosomal-dominant or recessive—

skeletal muscle actin, a chain

(ACTA1) gene; 1q42.1

Myotubular (centronuclear)

myopathy; X-linked (MTM1),

autosomal-recessive, or autosomaldominant

X-linked—myotubularin (MTM1)

gene; Xq28

X-linked form presents in infancy with

prominent hypotonia and poor prognosis;

autosomal forms have limb weakness and are

slowly progressive; autosomal-recessive form

is intermediate in severity and prognosis

Abundance of centrally located nuclei involving the

majority of muscle fibers; central nuclei are usually

confined to type 1 fibers, which are small in diameter,

but can occur in both fiber types

Autosomal-dominant—myogenic

factor 6 (MYF6) gene; 12q21

Autosomal-recessive—locus and gene

unknown

Malignant hyperpyrexia (malignant hyperthermia) is a rare clinical syndrome characterized by a dramatic hypermetabolic state (tachycardia, tachypnea, muscle spasms, and later

hyperpyrexia) triggered by the induction of anesthesia, usually with halogenated inhalational agents and succinylcholine. The clinical syndrome may also occur in predisposed

individuals with hereditary muscle diseases, including congenital myopathies, dystrophinopathies, and metabolic myopathies. The only reliable method of diagnosis is contraction of

biopsied muscle on exposure to anesthetic. Mutations in different genes have been identified in families with susceptibility to malignant hyperthermia, including genes encoding a

voltage-gated calcium channel (lq32), an L-type voltage-dependent calcium channel (7q21-q22), and a ryanodine receptor (19q13.1).[59]

Figure 27-12 A, Nemaline myopathy with numerous rod-shaped, intracytoplasmic inclusions (dark purple structures). B, Electron micrograph of subsarcolemmal nemaline bodies,

showing material of Z-band density.

Figure 27-13 A, Mitochondrial myopathy showing an irregular fiber with subsarcolemmal collections of mitochondria that stain red with the modified Gomori trichrome stain (ragged

red fiber). B, Electron micrograph of mitochondria from biopsy specimen in A showing "parking lot" inclusions.

Figure 27-14 A, Dermatomyositis. Note the rash affecting the eyelids. B, Dermatomyositis. The histologic appearance of muscle shows perifascicular atrophy of muscle fibers and

inflammation. C, Inclusion body myositis showing a vacuole within a myocyte. (Courtesy of Dr. Dennis Burns, Department of Pathology, University of Texas Southwestern Medical

School, Dallas, TX.)

References

1. Victor M, Ropper AH: Adams and Victor's Principles of Neurology, 7th ed. New York, McGraw-Hill, 2001, p 1465.

2. Pampheltt R, Sjarif A: Is quantitation necessary for assessment of sural nerve biopsies? Muscle & Nerve 27:562, 2003.

3. Bosboom WM, et al: Diagnostic value of sural nerve demyelination in chronic inflammatory demyelinating polyneuropathy. Brain 124:2427, 2001.

4. Hof PR, et al: The cellular components of nervous tissue. In Zigmond MJ, et al (eds): Fundamental Neuroscience. San Diego, Academic Press, 1999, p 56.

5. Gillespie CS, et al: Peripheral demyelination and neuropathic pain behavior in periaxin-deficient mice. Neuron 26:523, 2000.

6. Nagarajan R, et al: EGR2 mutations in inherited neuropathies dominant-negatively inhibit myelin gene expression. Neuron 30:35568, 2001.

7. Schnapp BJ: Trafficking of signaling modules by kinesin motors. J Cell Sci 116:2125, 2003.

8. Miller FD, Kaplan DR: On Trk for retrograde signaling. Neuron 32:767, 2001.

9. Smith CE, et al: Development of the blood-nerve barrier in neonatal rats. Microsurgery 21:290, 2001.

10. De Girolami U, Beggs AH: Skeletal muscle. In Silverberg SG, et al (eds): Principles and Practice of Surgical Pathology and Cytopathology. New York, Churchill Livingstone, 1997,

p. 943.

11. Dalkilic J, Kunkel LM: Muscular dystrophies: genes to pathogenesis. Curr Opin Genet Dev 13:23, 2003.

12. Carpenter S, Karpati G: Pathology of Skeletal Muscle, 2nd ed. Oxford, England, Oxford University Press, 2001, p 41.

13. DeVries GH: Schwann cell proliferation. In Dyck PJ, et al (eds): Peripheral Neuropathy. Philadelphia, WB Saunders, 1993, p 290.

14. Mueller M, et al: Rapid response of identified resident endoneurial macrophages to nerve injury. Am J Pathol 159:2187, 2001.

15. Gomes MD, et al: Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci U S A 98:14440, 2001.

16. Shah JV, Cleveland DW: Slow axonal transport: fast motors in the slow lane. Curr Opin Cell Biol 14:58, 2002.

17. Carpenter S, Karpati G: Pathology of Skeletal Muscle, 2nd ed. Oxford, England, Oxford University Press, 2001, p 662.

18. Govoni V, Granieri E: Epidemiology of the Guillain-Barré syndrome. Curr Opin Neurol 14:605, 2001.

19. Winer JB: Guillain Barré syndrome. Mol Pathol 54:381, 2001.

20. Kieseier BC, Hartung HP: Therapeutic strategies in the Guillain-Barré syndrome. Sem Neurol 23:159, 2003.

21. Stienekemeier M: Vaccination, prevention, and treatment of experimental autoimmune neuritis (EAN) by an oligomerized T cell epitope. Proc Nat Acad Sci 98:13872, 2001.

22. Hartung HP, et al: Progress in Guillain-Barré syndrome. Curr Opin Neurol 14:597, 2001.

23. Said G: Chronic inflammatory demyelinative polyneuropathy. J Neurol 249:245, 2002.

24. Piradov MA: Diphtheritic polyneuropathy: clinical analysis of severe forms. Arch Neurol 58:1438, 2001.

25. Kleinschmidt-DeMasters BK, Gilden DH: Varicella-zoster virus infections of the nervous system: clinical and pathologic correlates. Arch Pathol Lab Med 125:770, 2001.

26. Reilly MM: Classification of the hereditary motor and sensory neuropathies. Curr Opin Neurol 13:561, 2000.

27. Vallat JM: Dominantly inherited peripheral neuropathies. J Neuropath Exp Neurol 62:699, 2003.

28. Robaglia-Schlupp A, et al: PMP22 overexpression causes dysmyelination in mice. Brain 125:2213, 2002.

29. Norreel JC, et al: Close relationship between motor impairments and loss of functional motoneurons in a Charcot-Marie-Tooth type 1A model. Neurosci 116:695, 2003.

30. Street VA, et al: Mutation of a putative protein degradation gene LITAF/SIMPLE in Charcot-Marie-Tooth disease. Neurology 60:22, 2003.

31. Abrams CK: Pathogenesis of X-linked Charcot-Marie-Tooth disease: differential effects of two mutations in connexin 32. J Neurosci 23:10548, 2003.

32. Plante-Bordeneuve V, Said G: Dejerine-Sottas disease and hereditary demyelinating polyneuropathy of infancy. Muscle & Nerve 26:608, 2002.

33. Boerkoel CF, et al: EGR2 mutation R359W causes a spectrum of Dejerine-Sottas neuropathy. Neurogenetics 3:153, 2001.

34. Boerkoel CF, et al: Periaxin mutations cause recessive Dejerine-Sottas neuropathy. Am J Hum Genet 68:325, 2001.

35. Bertora P: Prevalence of subclinical neuropathy in diabetic patients: assessment by study of conduction velocity distribution within motor and sensory nerve fibres. J Neurol 245:81,

1998.

36. Thrainsdottir S: Endoneurial capillary abnormalities presage deterioration of glucose tolerance and accompany peripheral neuropathy in man. Diabetes 52:2615, 2003.

37. Dyck PJ, Giannini C: Pathologic alterations in the diabetic neuropathies of humans: a review. J Neuropathol Exp Neurol 55:1181, 1996.

38. Richardson EP, De Girolami U: Pathology of the Peripheral Nerve. Philadelphia, WB Saunders, 1995, p 78.

39. Koike H, et al: Alcoholic neuropathy is clinicopathologically distinct from thiamine-deficiency neuropathy. Ann Neurol 54:19, 2003.

40. Rauer S, et al: Quantification of circulating anti-Hu antibody in serial samples from patients with paraneoplastic neurological syndromes: possible correlation of antibody

concentration and course of neurological syndromes. J Neurol 249:285, 2002.

41. Musunuru K, Darnell RB: Paraneoplastic neurologic disease antigens: RNA-binding proteins and signaling proteins in neuronal degeneration. Annu Rev Neurosci 24:239, 2001.

42. Hughes R, et al: Carcinoma and the peripheral nervous system. J Neurol 243:371, 1996.

43. Steck AJ, et al: Paraproteinaemic neuropathies. Brain Pathol 9:361, 1999.

44. Spencer PS, Schaumburg HH: Experimental and Clinical Neurotoxicology, 2nd ed. New York, Oxford University Press, 2000, p 1310

45. Katz JN, Simmons BP: Carpal tunnel syndrome. New Engl J Med 346:1807, 2002.

46. Martin Y, et al: Genetic study of SMA patients without homozygous SMN1 deletions: identification of compound heterozygotes and characterisation of novel intragenic SMN1

mutations. Hum Genet 110:257, 2002.

47. Crawford TO: Spinal muscular atrophies. In Jones HR, DeVivo DC, Darras BT (eds): Neuromuscular Disorders of Infancy, Childhood, and Adolescence. Amsterdam, Butterworth

Heinemann. 2003, p 145.

48. Zatkova A, et al: Analysis of the SMN and NAIP genes in Slovak spinal muscular atrophy patients. Hum Hered 50:171, 2000.

49. Darras BT, et al: Dystrophinopathies. In Jones HR, et al (eds): Neuromuscular Disorders of Infancy, Childhood, and Adolescence. A Clinician's Approach. Philadelphia, Elsevier

Science, Inc., 2003, p. 649.

50. Burton EA, Davies KE: Muscular dystrophy: reason for optimism. Cell 108:5, 2002.

51. Anderson JL: Brain function in Duchenne muscular dystrophy. Brain 125:4, 2002.

52. Zatz M, et al: The 10 autosomal-recessive limb-girdle muscular dystrophies. Neuromuscular Disorders 13:532, 2003.

53. Mankodi A, Thornton CA: Myotonic syndromes. Curr Opin Neurol. 15:545, 2002.

54. Meola G: Clinical and genetic heterogeneity in myotonic dystrophies. Muscle Nerve 23:1789, 2000.

55. Mankodi A, et al: Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy. Mol Cell

10:35, 2002.

56. Liquori CL, et al: Myotonic dystrophy type 2 caused by a CCTG expansion in nitron 1 of ZNF9. Science 293:864, 2001.

57. Tawil R, et al: Channelopathies. In Pulst SM (ed): Neurogenetics. New York, Oxford University Press, 2000, p 45.

58. Davies NP, Hanna MG: The skeletal muscle channelopathies: distinct entities and overlapping syndromes. Curr Opin Neurol 16:559, 2003.

59. McCarthy TV, et al: Ryanodine receptor mutations in malignant hyperthermia and central core disease. Hum Mutat 15:410, 2000.

60. Tubridy N, et al: Congenital myopathies and congenital muscular dystrophies. Curr Opin Neurol 14:575, 2001.

61. Vladutiu GD: Laboratory diagnosis of metabolic myopathies. Muscle Nerve 25:649, 2002.

62. Weller RO, et al: Diseases of muscle. In Graham DI, Lantos PL (eds): Greenfield's Neuropathology, Vol 2, 7th ed. London, Oxford University Press, 2002, p 667

63. Roe CR, Ding J: Mitochondrial fatty acid oxidation disorders. In Scriver CR, et al (eds): The metabolic and Molecular Bases of Inherited Disease, 8th ed. New York, McGraw-Hill,

2001, p 2297.

64. Lahjouji K, et al: Carnitine transport by organic cation transporters and systemic carnitine deficiency. Mol Genet Metab 73:287, 2001.

65. Bodman M, et al: Medium-chain acyl coenzyme A dehydrogenase deficiency: occurrence in an infant and his father. Arch Neurol 58:811, 2001.

66. DiMauro S, Schon EA: Mitochondrial respiratory-chain diseases. N Engl J Med 348:2656, 2003.

67. Shoffner JM: Oxidative phosphorylation diseases. In Scriver CR, et al (eds): The Metabolic and Molecular Bases of Inherited Disease, 8th ed. New York, McGraw-Hill, 2001, p

2367.

68. Wallace DC, et al: Mitochondria and neuro-ophthalmologic diseases. In Scriver CR, et al (eds): The Metabolic and Molecular Bases of Inherited Disease, 8th ed. New York,

McGraw-Hill, 2001, p 2425.

69. Vogel H: Mitochondrial myopathies and the role of the pathologist in the molecular era. J Neuropathol Exp Neurol 60:217, 2001.

70. Oldfors A, Tulinius M: Mitochondrial encephalomyopathies. J Neuropathol Exp Neurol. 62:217, 2003.

71. Dalakas MC, Hohlfeld R: Polymyositis and dermatomyositis. Lancet 362:971, 2003.

72. Buchbinder R, et al: Incidence of malignant disease in biopsy-proven inflammatory myopathy. Ann Intern Med 134:1087, 2001.

73. Ramanan AV, Feldman RM: Clinical outcomes in juvenile dermatomyositis. Curr Opin Rheumatol 14:658, 2002.

74. Askanas V, Engel WK: Inclusion-body myositis and myopathies: different etiologies, possibly similar pathogenetic mechanisms. Curr Opin Neurol 15:525, 2002.

75. Ellis RJ, Pinheiro TJJ: Danger: misfolding proteins. Nature 416:483, 2002.

76. Kanda F, et al: Steroid myopathy: pathogenesis and effects of growth hormone and insulin-like growth factor-I administration. Hormone Res 56 (suppl 1):24, 2001.

77. Stein M, et al: Hydroxychloroquine neuromyotoxicity. J Rheum 27:2927, 2000.

78. Poulas K, et al: Equal male and female incidence of myasthenia gravis. Neurol 54:1202, 2000.

79. Ricny J, et al: Determination of anti-acetylcholine receptor antibodies in myasthenic patients by use of time-resolved fluorescence. Clin Chem 48:549, 2002.

80. Palace J, et al: Myasthenia gravis: diagnostic and management dilemmas. Curr Opin Neurol 14:583, 2001.

81. Younger DS, Raksadawan N: Medical therapies in myasthenia gravis. Chest Surg Clin North Am 11:329, 2001.

82. Pascuzzi RM: Myasthenia gravis and Lambert-Eaton syndrome. Ther Apher 6:57, 2002.

83. Pinto A, et al: The action of Lambert-Eaton myasthenic syndrome immunoglobulin G on cloned human voltage-gated calcium channels. Muscle Nerve 25:715, 2002.

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