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Congenital Myopathies

  • Author: Glenn Lopate, MD; Chief Editor: Amy Kao, MD  more...
 
Updated: Aug 13, 2014
 

Background

The first report of a congenital myopathy was in 1956, when a patient with central core disease (CCD) was described. Since that time, other myopathies have been defined as congenital myopathies, which have the following characteristics:

  • Onset in early life with hypotonia, hyporeflexia, generalized weakness that is more often proximal than distal, and poor muscle bulk
  • Often with dysmorphic features that may be secondary to the weakness
  • Relatively nonprogressive
  • Hereditary
  • Unique morphological features on histochemical or ultrastructural examination of the muscle biopsy sample that originate within the myofiber

Hypotonia is the clinical hallmark of congenital myopathies. It presents in the neonatal period as head lag; lack of flexion of the hips, knees, and elbows; external rotation of the hips; diffuse weakness in facial, limb, and axial muscles; and reduced muscle mass.

The above features do not apply to all cases of congenital myopathy. Some cases have been reported as adult onset or as a progressive course. Some of the morphological alterations are not disease specific but are seen in various congenital myopathies or in other myopathic or nonmyopathic conditions.

A recent review article[1] divided the congenital myopathies based on genetic and morphological features into 4 main groups.

Myopathies with protein accumulation

  • Nemaline myopathy
  • Myosin storage myopathy
  • Cap disease
  • Reducing body myopathy

Myopathies with cores

  • Central core disease
  • Core-rod myopathy
  • Multiminicore disease

Myopathies with central nuclei

  • Myotubular myopathy
  • Centronuclear myopathy

Myopathies with fiber size variation

  • Congenital fiber type disproportion

With the advent of improved techniques such as electron microscopy, enzyme histochemistry, immunocytochemistry, and molecular genetics, the etiologies of many congenital myopathies are now well defined. This article focuses on the diseases with known mutations. The numerous rare congenital myopathies distinguished primarily based on a unique morphological feature on muscle biopsy are briefly discussed below (see Rare congenital myopathies).

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Pathophysiology

In the common, well-described congenital myopathies, mutations have been identified in genes that encode for muscle proteins. The loss or dysfunction of these proteins presumably leads to the specific morphological feature on muscle biopsy samples and to the clinical muscle disease. The specific pathogenesis for each congenital myopathy is discussed below.

The same principle presumably leads to the morphological features determined by muscle biopsy in congenital myopathies whose genetic defects are not yet known.

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Epidemiology

Frequency

International

The true incidence of congenital myopathies is unknown. In a series of 250 infants with neonatal hypotonia described by Fardeau and Tome, muscle biopsy performed before age 2 months revealed that only 14% had a congenital myopathy. Central nervous system (CNS) disease is the most common cause of congenital hypotonia.

The same authors documented 180 cases of congenital myopathy over 20 years. The types were as follows:

  • Nemaline rod myopathy (20%)
  • Central core disease (16%)
  • Centronuclear myopathy (14%)
  • Multiminicore myopathy (10%)
  • Congenital fiber-type disproportion or type 1 fiber predominance (21%)
  • Six other miscellaneous congenital myopathies (19%)

Mortality/Morbidity

Associated morbidity and mortality rates have considerable variability.

  • Some patients die within the neonatal period, while others can have a normal life span.
  • Cardiopulmonary compromise is the most common cause of death.
  • Other complications include skeletal deformities and malignant hyperthermia.

Sex

Both sexes are affected equally in most congenital myopathies since inheritance is usually autosomal recessive or autosomal dominant.

In X-linked forms, boys are affected almost exclusively, although occasional female carriers with clinical manifestations have been described.

Age

Congenital myopathies usually present in the neonatal period but can also present later in life (even into adulthood).

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Contributor Information and Disclosures
Author

Glenn Lopate, MD Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, Washington University School of Medicine; Consulting Staff, Department of Neurology, Barnes-Jewish Hospital

Glenn Lopate, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, Phi Beta Kappa

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Kenneth J Mack, MD, PhD Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic

Kenneth J Mack, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Phi Beta Kappa, Society for Neuroscience

Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD Attending Neurologist, Children's National Medical Center

Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, Child Neurology Society

Disclosure: Have stock from Cellectar Biosciences; have stock from Varian medical systems; have stock from Express Scripts.

Additional Contributors

Robert J Baumann, MD Professor of Neurology and Pediatrics, Department of Neurology, University of Kentucky College of Medicine

Robert J Baumann, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, Child Neurology Society

Disclosure: Nothing to disclose.

References
  1. North K. What's new in congenital myopathies?. Neuromuscul Disord. 2008 Jun. 18(6):433-42. [Medline].

  2. Klein A, Jungblath H, Clement E, Lillis S, Abbs S, Munot P, et al. Muscle Magnetic Resonance Imaging in Congenital Myopathies due to Ryanodine Receptor Type 1 Gene Mutations. Arch Neurol. Sep 2011. 68:1171-1179.

  3. Monnier N, Romero NB, Lerale J, Nivoche Y, Qi D, MacLennan DH. An autosomal dominant congenital myopathy with cores and rods is associated with a neomutation in the RYR1 gene encoding the skeletal muscle ryanodine receptor. Hum Mol Genet. 2000 Nov 1. 9(18):2599-608. [Medline].

  4. Scacheri PC, Hoffman EP, Fratkin JD, Semino-Mora C, Senchak A, Davis MR, et al. A novel ryanodine receptor gene mutation causing both cores and rods in congenital myopathy. Neurology. 2000 Dec 12. 55(11):1689-96. [Medline].

  5. Hernandez-Lain A, Husson I, Monnier N, Farnoux C, Brochier G, Lacène E, et al. De novo RYR1 heterozygous mutation (I4898T) causing lethal core-rod myopathy in twins. Eur J Med Genet. 2011 Jan-Feb. 54(1):29-33. [Medline].

  6. Wilmshurst JM, Lillis S, Zhou H, Pillay K, Henderson H, Kress W. RYR1 mutations are a common cause of congenital myopathies with central nuclei. Ann Neurol. 2010 Nov. 68(5):717-26. [Medline].

  7. Sato I, Wu S, Ibarra MC, Hayashi YK, Fujita H, Tojo M. Congenital neuromuscular disease with uniform type 1 fiber and RYR1 mutation. Neurology. 2008 Jan 8. 70(2):114-22. [Medline].

  8. Tammaro A, Di Martino A, Bracco A, Cozzolino S, Savoia G, Andria B. Novel missense mutations and unexpected multiple changes of RYR1 gene in 75 malignant hyperthermia families. Clin Genet. 2011 May. 79(5):438-47. [Medline].

  9. Duarte ST, Oliveira J, Santos R, Pereira P, Barroso C, Conceição I, et al. Dominant and recessive RYR1 mutations in adults with core lesions and mild muscle symptoms. Muscle Nerve. 2011 Jul. 44(1):102-8. [Medline].

  10. Wattanasirichaigoon D, Swoboda KJ, Takada F, et al. Mutations of the slow muscle alpha-tropomyosin gene, TPM3, are a rare cause of nemaline myopathy. Neurology. 2002 Aug 27. 59(4):613-7. [Medline].

  11. Wallgren-Pettersson C, Clarke A, Samson F, et al. The myotubular myopathies: differential diagnosis of the X linked recessive, autosomal dominant, and autosomal recessive forms and present state of DNA studies. J Med Genet. 1995 Sep. 32(9):673-9. [Medline].

  12. Lehtokari VL, Pelin K, Sandbacka M, et al. Identification of 45 novel mutations in the nebulin gene associated with autosomal recessive nemaline myopathy. Hum Mutat. 2006 Sep. 27(9):946-56. [Medline].

  13. Agrawal PB, Strickland CD, Midgett C, et al. Heterogeneity of nemaline myopathy cases with skeletal muscle alpha-actin gene mutations. Ann Neurol. 2004 Jul. 56(1):86-96. [Medline].

  14. Laing NG, Dye DE, Wallgren-Pettersson C, Richard G, Monnier N, Lillis S, et al. Mutations and polymorphisms of the skeletal muscle alpha-actin gene (ACTA1). Hum Mutat. 2009 Sep. 30(9):1267-77. [Medline]. [Full Text].

  15. Hutchinson DO, Charlton A, Laing NG, Ilkovski B, North KN. Autosomal dominant nemaline myopathy with intranuclear rods due to mutation of the skeletal muscle ACTA1 gene: clinical and pathological variability within a kindred. Neuromuscul Disord. 2006 Feb. 16(2):113-21. [Medline].

  16. Bornemann A, Petersen MB, Schmalbruch H. Fatal congenital myopathy with actin filament deposits. Acta Neuropathol. 1996 Jul. 92(1):104-8. [Medline].

  17. Kaindl AM, Rüschendorf F, Krause S, Goebel HH, Koehler K, Becker C, et al. Missense mutations of ACTA1 cause dominant congenital myopathy with cores. J Med Genet. 2004 Nov. 41(11):842-8. [Medline]. [Full Text].

  18. Monnier N, Lunardi J, Marty I, Mezin P, Labarre-Vila A, Dieterich K, et al. Absence of beta-tropomyosin is a new cause of Escobar syndrome associated with nemaline myopathy. Neuromuscul Disord. 2009 Feb. 19(2):118-23. [Medline].

  19. Lehtokari VL, Ceuterick-de Groote C, de Jonghe P, et al. Cap disease caused by heterozygous deletion of the beta-tropomyosin gene TPM2. Neuromuscul Disord. 2007 Jun. 17(6):433-42. [Medline].

  20. Sung SS, Brassington AM, Grannatt K, Rutherford A, Whitby FG, Krakowiak PA, et al. Mutations in genes encoding fast-twitch contractile proteins cause distal arthrogryposis syndromes. Am J Hum Genet. 2003 Mar. 72(3):681-90. [Medline]. [Full Text].

  21. Johnston JJ, Kelley RI, Crawford TO, et al. A novel nemaline myopathy in the Amish caused by a mutation in troponin T1. Am J Hum Genet. 2000 Oct. 67(4):814-21. [Medline].

  22. Sambuughin N, Yau KS, Olivé M, Duff RM, Bayarsaikhan M, Lu S. Dominant mutations in KBTBD13, a member of the BTB/Kelch family, cause nemaline myopathy with cores. Am J Hum Genet. 2010 Dec 10. 87(6):842-7. [Medline].

  23. Agrawal PB, Greenleaf RS, Tomczak KK, et al. Nemaline myopathy with minicores caused by mutation of the CFL2 gene encoding the skeletal muscle actin-binding protein, cofilin-2. Am J Hum Genet. 2007 Jan. 80(1):162-7. [Medline].

  24. Bitoun M, Bevilacqua JA, Prudhon B, et al. Dynamin 2 mutations cause sporadic centronuclear myopathy with neonatal onset. Ann Neurol. 2007 Dec. 62(6):666-70. [Medline].

  25. Bitoun M, Maugenre S, Jeannet PY, et al. Mutations in dynamin 2 cause dominant centronuclear myopathy. Nat Genet. 2005 Nov. 37(11):1207-9. [Medline].

  26. Amburgey K, McNamara N, Bennett LR, McCormick ME, Acsadi G, Dowling JJ. Prevalence of congenital myopathies in a representative pediatric united states population. Ann Neurol. 2011 Oct. 70(4):662-5. [Medline].

  27. Biancalana V, Beggs AH, Das S, et al. Clinical utility gene card for: Centronuclear and myotubular myopathies. Eur J Hum Genet. 2012 May 23. [Medline].

  28. Susman RD, Quijano-Roy S, Yang N, Webster R, Clarke NF, Dowling J. Expanding the clinical, pathological and MRI phenotype of DNM2-related centronuclear myopathy. Neuromuscul Disord. 2010 Apr. 20(4):229-37. [Medline].

  29. Hanisch F, Müller T, Dietz A, Bitoun M, Kress W, Weis J. Phenotype variability and histopathological findings in centronuclear myopathy due to DNM2 mutations. J Neurol. 2011 Jun. 258(6):1085-90. [Medline].

  30. Laporte J, Guiraud-Chaumeil C, Vincent MC, et al. Mutations in the MTM1 gene implicated in X-linked myotubular myopathy. ENMC International Consortium on Myotubular Myopathy. European Neuro-Muscular Center. Hum Mol Genet. 1997 Sep. 6(9):1505-11. [Medline].

  31. Nicot AS, Toussaint A, Tosch V, et al. Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy. Nat Genet. 2007 Sep. 39(9):1134-9. [Medline].

  32. Schara U, Kress W, Bonnemann CG, et al. The phenotype and long-term follow-up in 11 patients with juvenile selenoprotein N1-related myopathy. Eur J Paediatr Neurol. 2008 May. 12(3):224-30. [Medline].

  33. Clarke NF, Kolski H, Dye DE, et al. Mutations in TPM3 are a common cause of congenital fiber type disproportion. Ann Neurol. 2008 Mar. 63(3):329-37. [Medline].

  34. Clarke NF, Kidson W, Quijano-Roy S, et al. SEPN1: associated with congenital fiber-type disproportion and insulin resistance. Ann Neurol. 2006 Mar. 59(3):546-52. [Medline].

  35. Laing NG, Clarke NF, Dye DE, et al. Actin mutations are one cause of congenital fibre type disproportion. Ann Neurol. 2004 Nov. 56(5):689-94. [Medline].

  36. Clarke NF, Waddell LB, Cooper ST, Perry M, Smith RL, Kornberg AJ, et al. Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion. Hum Mutat. 2010 Jul. 31(7):E1544-50. [Medline].

  37. Pegoraro E, Gavassini BF, Borsato C, et al. MYH7 gene mutation in myosin storage myopathy and scapulo-peroneal myopathy. Neuromuscul Disord. 2007 Apr. 17(4):321-9. [Medline].

  38. Uro-Coste E, Arné-Bes MC, Pellissier JF, Richard P, Levade T, Heitz F. Striking phenotypic variability in two familial cases of myosin storage myopathy with a MYH7 Leu1793pro mutation. Neuromuscul Disord. 2009 Feb. 19(2):163-6. [Medline].

  39. Ortolano S, Tarrío R, Blanco-Arias P, Teijeira S, Rodríguez-Trelles F, García-Murias M. A novel MYH7 mutation links congenital fiber type disproportion and myosin storage myopathy. Neuromuscul Disord. 2011 Apr. 21(4):254-62. [Medline].

  40. Schoser BG, Frosk P, Engel AG, Klutzny U, Lochmuller H, Wrogemann K. Commonality of TRIM32 mutation in causing sarcotubular myopathy and LGMD2H. Ann Neurol. 2005 Apr. 57(4):591-5. [Medline].

  41. Cowling BS, Cottle DL, Wilding BR, D'Arcy CE, Mitchell CA, McGrath MJ. Four and a half LIM protein 1 gene mutations cause four distinct human myopathies: a comprehensive review of the clinical, histological and pathological features. Neuromuscul Disord. 2011 Apr. 21(4):237-51. [Medline].

  42. Schessl J, Zou Y, McGrath MJ, et al. Proteomic identification of FHL1 as the protein mutated in human reducing body myopathy. J Clin Invest. 2008 Mar. 118(3):904-12. [Medline].

  43. Quinzii CM, Vu TH, Min KC, Tanji K, Barral S, Grewal RP, et al. X-linked dominant scapuloperoneal myopathy is due to a mutation in the gene encoding four-and-a-half-LIM protein 1. Am J Hum Genet. 2008 Jan. 82(1):208-13. [Medline]. [Full Text].

  44. Windpassinger C, Schoser B, Straub V, et al. An X-linked myopathy with postural muscle atrophy and generalized hypertrophy, termed XMPMA, is caused by mutations in FHL1. Am J Hum Genet. 2008 Jan. 82(1):88-99. [Medline].

  45. Gueneau L, Bertrand AT, Jais JP, Salih MA, Stojkovic T, Wehnert M, et al. Mutations of the FHL1 gene cause Emery-Dreifuss muscular dystrophy. Am J Hum Genet. 2009 Sep. 85(3):338-53. [Medline]. [Full Text].

  46. Shalaby S, Hayashi YK, Goto K, Ogawa M, Nonaka I, Noguchi S. Rigid spine syndrome caused by a novel mutation in four-and-a-half LIM domain 1 gene (FHL1). Neuromuscul Disord. 2008 Dec. 18(12):959-61. [Medline].

  47. Foroud T, Pankratz N, Batchman AP, et al. A mutation in myotilin causes spheroid body myopathy. Neurology. 2005 Dec 27. 65(12):1936-40. [Medline].

  48. Maclennan DH, Zvaritch E. Mechanistic models for muscle diseases and disorders originating in the sarcoplasmic reticulum. Biochim Biophys Acta. 2011 May. 1813(5):948-64. [Medline].

  49. Zhou H, Jungbluth H, Sewry CA, et al. Molecular mechanisms and phenotypic variation in RYR1-related congenital myopathies. Brain. 2007 Aug. 130:2024-36. [Medline].

  50. Corbett MA, Akkari PA, Domazetovska A, et al. An alphaTropomyosin mutation alters dimer preference in nemaline myopathy. Ann Neurol. 2005 Jan. 57(1):42-9. [Medline].

  51. Michele DE, Albayya FP, Metzger JM. A nemaline myopathy mutation in alpha-tropomyosin causes defective regulation of striated muscle force production. J Clin Invest. 1999 Dec. 104(11):1575-81. [Medline].

  52. Moraczewska J, Greenfield NJ, Liu Y, Hitchcock-DeGregori SE. Alteration of tropomyosin function and folding by a nemaline myopathy-causing mutation. Biophys J. 2000 Dec. 79(6):3217-25. [Medline].

  53. Jin JP, Brotto MA, Hossain MM, Huang QQ, Brotto LS, Nosek TM. Truncation by Glu180 nonsense mutation results in complete loss of slow skeletal muscle troponin T in a lethal nemaline myopathy. J Biol Chem. 2003 Jul 11. 278(28):26159-65. [Medline].

  54. Dowling JJ, Gibbs EM, Feldman EL. Membrane traffic and muscle: lessons from human disease. Traffic. 2008 Jul. 9(7):1035-43. [Medline].

  55. Romero NB. Centronuclear myopathies: a widening concept. Neuromuscul Disord. 2010 Apr. 20(4):223-8. [Medline].

  56. Liewluck T, Lovell TL, Bite AV, Engel AG. Sporadic centronuclear myopathy with muscle pseudohypertrophy, neutropenia, and necklace fibers due to a DNM2 mutation. Neuromuscul Disord. 2010 Dec. 20(12):801-4. [Medline]. [Full Text].

  57. Bevilacqua JA, Bitoun M, Biancalana V, Oldfors A, Stoltenburg G, Claeys KG. "Necklace" fibers, a new histological marker of late-onset MTM1-related centronuclear myopathy. Acta Neuropathol. 2009 Mar. 117(3):283-91. [Medline].

  58. Zorzato F, Jungbluth H, Zhou H, Muntoni F, Treves S. Functional effects of mutations identified in patients with multiminicore disease. IUBMB Life. 2007 Jan. 59(1):14-20. [Medline].

  59. Clarke NF, Ilkovski B, Cooper S, et al. The pathogenesis of ACTA1-related congenital fiber type disproportion. Ann Neurol. 2007 Jun. 61(6):552-61. [Medline].

  60. Kudryashova E, Kudryashov D, Kramerova I, Spencer MJ. Trim32 is a ubiquitin ligase mutated in limb girdle muscular dystrophy type 2H that binds to skeletal muscle myosin and ubiquitinates actin. J Mol Biol. 2005 Nov 25. 354(2):413-24. [Medline].

  61. Brooke MH, Engel WK. The histographic analysis of human muscle biopsies with regard to fiber types. 4. Children's biopsies. Neurology. 1969 Jun. 19(6):591-605. [Medline].

  62. Donner K, Ollikainen M, Ridanpaa M, et al. Mutations in the beta-tropomyosin (TPM2) gene--a rare cause of nemaline myopathy. Neuromuscul Disord. 2002 Feb. 12(2):151-8. [Medline].

  63. Engel AG, Gomez MR, Groover RV. Multicore disease. A recently recognized congenital myopathy associated with multifocal degeneration of muscle fibers. Mayo Clin Proc. 1971 Oct. 46(10):666-81. [Medline].

  64. Engel WK. Mitochondrial aggregates in muscle disease. J Histochem Cytochem. 1964 Jan. 12:46-8. [Medline].

  65. Goebel HH. Congenital myopathies at their molecular dawning. Muscle Nerve. 2003 May. 27(5):527-48. [Medline].

  66. Goldfarb LG, Park KY, Cervenakova L, et al. Missense mutations in desmin associated with familial cardiac and skeletal myopathy. Nat Genet. 1998 Aug. 19(4):402-3. [Medline].

  67. Griggs RC, Mendell JR, Miller RG. Congenital myopathies. Evaluation and Treatment of Myopathies. Philadelphia: FA Davis Co; 1995. 211-46.

  68. Herman GE, Finegold M, Zhao W, de Gouyon B, Metzenberg A. Medical complications in long-term survivors with X-linked myotubular myopathy. J Pediatr. 1999 Feb. 134(2):206-14. [Medline].

  69. Laing NG, Wilton SD, Akkari PA, et al. A mutation in the alpha tropomyosin gene TPM3 associated with autosomal dominant nemaline myopathy. Nat Genet. 1995 Jan. 9(1):75-9. [Medline].

  70. Loke J, MacLennan DH. Malignant hyperthermia and central core disease: disorders of Ca2+ release channels. Am J Med. 1998 May. 104(5):470-86. [Medline].

  71. McEntagart M, Parsons G, Buj-Bello A, et al. Genotype-phenotype correlations in X-linked myotubular myopathy. Neuromuscul Disord. 2002 Dec. 12(10):939-46. [Medline].

  72. North K. Congenital myopathies. Engel AG, Franzini-Armstrong C, eds. Myology. 3rd ed. New York, NY: McGraw Hill; 2004. 1473-1533.

  73. Nowak KJ, Wattanasirichaigoon D, Goebel HH, et al. Mutations in the skeletal muscle alpha-actin gene in patients with actin myopathy and nemaline myopathy. Nat Genet. 1999 Oct. 23(2):208-12. [Medline].

  74. Pelin K, Hilpela P, Donner K, et al. Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy. Proc Natl Acad Sci U S A. 1999 Mar 2. 96(5):2305-10. [Medline].

  75. Quane KA, Healy JM, Keating KE, et al. Mutations in the ryanodine receptor gene in central core disease and malignant hyperthermia. Nat Genet. 1993 Sep. 5(1):51-5. [Medline].

  76. Ryan MM, Schnell C, Strickland CD, et al. Nemaline myopathy: a clinical study of 143 cases. Ann Neurol. 2001 Sep. 50(3):312-20. [Medline].

  77. Shuaib A, Paasuke RT, Brownell KW. Central core disease. Clinical features in 13 patients. Medicine (Baltimore). 1987 Sep. 66(5):389-96. [Medline].

  78. Tajsharghi H, Thornell LE, Lindberg C, Lindvall B, Henriksson KG, Oldfors A. Myosin storage myopathy associated with a heterozygous missense mutation in MYH7. Ann Neurol. 2003 Oct. 54(4):494-500. [Medline].

  79. Vicart P, Caron A, Guicheney P, et al. A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy. Nat Genet. 1998 Sep. 20(1):92-5. [Medline].

  80. Wallgren-Pettersson C, Laing NG. Report of the 70th ENMC International Workshop: nemaline myopathy, 11-13 June 1999, Naarden, The Netherlands. Neuromuscul Disord. 2000 Jun. 10(4-5):299-306. [Medline].

  81. Zhang Y, Chen HS, Khanna VK, et al. A mutation in the human ryanodine receptor gene associated with central core disease. Nat Genet. 1993 Sep. 5(1):46-50. [Medline].

  82. Ravenscroft G, Miyatake S, Lehtokari VL, Todd EJ, Vornanen P, Yau KS. Mutations in KLHL40 are a frequent cause of severe autosomal-recessive nemaline myopathy. Am J Hum Genet. 2013 Jul 11. 93(1):6-18. [Medline].

  83. Kondo E, Nishimura T, Kosho T, Inaba Y, Mitsuhashi S, Ishida T, et al. Recessive RYR1 mutations in a patient with severe congenital nemaline myopathy with ophthalomoplegia identified through massively parallel sequencing. Am J Med Genet A. 2012 Apr. 158A(4):772-8. [Medline].

  84. Gupta VA, Ravenscroft G, Shaheen R, Todd EJ, Swanson LC, Shiina M, et al. Identification of KLHL41 Mutations Implicates BTB-Kelch-Mediated Ubiquitination as an Alternate Pathway to Myofibrillar Disruption in Nemaline Myopathy. Am J Hum Genet. 2013 Dec 5. 93(6):1108-17. [Medline]. [Full Text].

  85. Kerst B, Mennerich D, Schuelke M, Stoltenburg-Didinger G, von Moers A, Gossrau R. Heterozygous myogenic factor 6 mutation associated with myopathy and severe course of Becker muscular dystrophy. Neuromuscul Disord. 2000 Dec. 10(8):572-7. [Medline].

  86. Majczenko K, Davidson AE, Camelo-Piragua S, Agrawal PB, Manfready RA, Li X. Dominant mutation of CCDC78 in a unique congenital myopathy with prominent internal nuclei and atypical cores. Am J Hum Genet. 2012 Aug 10. 91(2):365-71. [Medline].

  87. Ceyhan-Birsoy O, Agrawal PB, Hidalgo C, Schmitz-Abe K, DeChene ET, Swanson LC. Recessive truncating titin gene, TTN, mutations presenting as centronuclear myopathy. Neurology. 2013 Oct 1. 81(14):1205-14. [Medline].

  88. Tein I, Elpeleg O, Ben-Zeev B, Korman SH, Lossos A, Lev D. Short-chain acyl-CoA dehydrogenase gene mutation (c.319C>T) presents with clinical heterogeneity and is candidate founder mutation in individuals of Ashkenazi Jewish origin. Mol Genet Metab. 2008 Feb. 93(2):179-89. [Medline].

  89. Boyden SE, Mahoney LJ, Kawahara G, Myers JA, Mitsuhashi S, Estrella EA, et al. Mutations in the satellite cell gene MEGF10 cause a recessive congenital myopathy with minicores. Neurogenetics. 2012 May. 13(2):115-24. [Medline]. [Full Text].

  90. Schoenmakers E, Agostini M, Mitchell C, Schoenmakers N, Papp L, Rajanayagam O. Mutations in the selenocysteine insertion sequence-binding protein 2 gene lead to a multisystem selenoprotein deficiency disorder in humans. J Clin Invest. 2010 Dec. 120(12):4220-35. [Medline].

  91. Carmignac V, Salih MA, Quijano-Roy S, Marchand S, Al Rayess MM, Mukhtar MM. C-terminal titin deletions cause a novel early-onset myopathy with fatal cardiomyopathy. Ann Neurol. 2007 Apr. 61(4):340-51. [Medline].

  92. Cullup T, Lamont PJ, Cirak S, Damian MS, Wallefeld W, Gooding R. Mutations in MYH7 cause Multi-minicore Disease (MmD) with variable cardiac involvement. Neuromuscul Disord. 2012 Dec. 22(12):1096-104. [Medline].

  93. Clarke NF, Waddell LB, Sie LT, van Bon BW, McLean C, Clark D, et al. Mutations in TPM2 and congenital fibre type disproportion. Neuromuscul Disord. 2012 Nov. 22(11):955-8. [Medline].

  94. Clarke NF, Amburgey K, Teener J, Camelo-Piragua S, Kesari A, Punetha J. A novel mutation expands the genetic and clinical spectrum of MYH7-related myopathies. Neuromuscul Disord. 2013 May. 23(5):432-6. [Medline].

 
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Central core disease, nicotinamide adenine dinucleotide (NADH) stain. In the central core, mitochondria and oxidative enzymes are absent. Cores are also present on cytochrome oxidase and succinate dehydrogenase (SDH) stains.
Nemaline rod myopathy, Gomori trichrome (GT) stain. Dark blue structures are seen only with this stain. They contain Z disk material, including alpha-actinin and tropomyosin.
Centronuclear myopathy, hematoxylin and eosin stain. Note the numerous, centrally placed nuclei. Normal nuclei are at the periphery of the muscle fiber.
Tubular aggregates, nicotinamide adenine dinucleotide (NADH) stain. Cytoplasmic collections of membranous tubules (derived from the sarcoplasmic reticulum) can be present in various myopathies, including myopathy with tubular aggregates, hypokalemic periodic paralysis, malignant hyperthermia, myotonia congenita, and ceratin toxic myopathies.
 
 
 
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