eMedicine Specialties > Neurology > Pediatric Neurology

Congenital Myopathies: Differential Diagnoses & Workup

Author: Glenn Lopate, MD, Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, Washington University School of Medicine; Chief of Neurology, St Louis ConnectCare, Consulting Staff, Barnes Jewish Hospital
Contributor Information and Disclosures

Updated: May 26, 2009

Differential Diagnoses

Cerebral Palsy
Congenital Muscular Dystrophy
Limb-Girdle Muscular Dystrophy
Metabolic Myopathies
Myasthenia Gravis
Spinal Muscular Atrophy

Other Problems to Be Considered

Congenital myotonic dystrophy
Congenital myasthenic syndromes
Mitochondrial cytopathies
Myotonic diseases
Fascioscapulohumeral dystrophy
Congenital hypomyelinating neuropathies

Workup

Laboratory Studies

  • Creatine kinase level
    • Creatine kinase (CK) level is either in the reference range or mildly elevated in all of the congenital myopathies.
    • It can be elevated moderately in central core disease (CCD) and may also be elevated in asymptomatic carriers of the ryanodine receptor mutation in CCD.
    • If the CK level is very high, other disorders such as Duchenne-Becker or limb-girdle muscular dystrophy, should be considered.

Other Tests

  • Electromyography and nerve conduction studies
    • Electromyography (EMG) and nerve conduction studies (NCSs) should be performed in all patients in whom a congenital myopathy is suspected.
    • In the differential diagnosis, rule out other diseases such as spinal muscular atrophy, congenital myasthenia, and hereditary neuropathy.
    • In congenital myopathy, NCS findings are normal and EMG findings are either normal or show the typical small-amplitude, narrow-duration motor unit potentials (MUPs) that are seen in myopathies. Fibrillations and positive sharp waves are rare.
  • Electrocardiography (ECG): Cardiac disease may be prominent in nemaline myopathy or, at times, in other congenital myopathies. Obtain ECG when considering these diagnoses.

Procedures

  • Muscle biopsy
    • Obtain a muscle biopsy in all patients in whom a congenital myopathy is suspected. Pathological examination should be performed at a center whose staff has expertise in muscle pathology.
    • Other causes of weakness need to be ruled out. In addition, the morphologic characteristics necessary to make the diagnosis need to be established.
    • Ultrastructural examination of muscle is often necessary, since several of the pathologic features are based on the EM appearance of muscle.

More on Congenital Myopathies

Overview: Congenital Myopathies
Differential Diagnoses & Workup: Congenital Myopathies
Treatment & Medication: Congenital Myopathies
Follow-up: Congenital Myopathies
Multimedia: Congenital Myopathies
References
[ CLOSE WINDOW ]

References

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

  2. 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. Aug 27 2002;59(4):613-7. [Medline].

  3. 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. Sep 1995;32(9):673-9. [Medline].

  4. 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. Sep 2006;27(9):946-56. [Medline].

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

  6. 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. Feb 2006;16(2):113-21. [Medline].

  7. 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. Jun 2007;17(6):433-42. [Medline].

  8. 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. Oct 2000;67(4):814-21. [Medline].

  9. 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. Jan 2007;80(1):162-7. [Medline].

  10. 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. Sep 2007;39(9):1134-9. [Medline].

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

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

  13. 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. May 2008;12(3):224-30. [Medline].

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

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

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

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

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

  19. 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. Jan 2008;82(1):88-99. [Medline].

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

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

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

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

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

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

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

  27. 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. Nov 25 2005;354(2):413-24. [Medline].

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

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

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

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

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

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

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

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

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

  37. 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. Sep 1997;6(9):1505-11. [Medline].

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

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

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

  41. 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. Oct 1999;23(2):208-12. [Medline].

  42. 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. Mar 2 1999;96(5):2305-10. [Medline].

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

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

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

  46. 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. Oct 2003;54(4):494-500. [Medline].

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

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

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

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

congenital myopathy, congenital myopathies, broad A-band disease, cap myopathy, central core disease, CCD, congenital fiber type disproportion, congential myopathy with apoptotic changes, congenital myopathy with mosaic fibers and interlacing sarcomeres, cylindrical spirals myopathy, fingerprint body myopathy, hyaline body (myosin storage) myopathy, lamellar body myopathy, multiminicore disease, myopathy with hexagonally cross-linked tubular arrays, myopathy with muscle spindle excess, myopathy with tubular aggregates, myotubular/centronuclear myopathy, nemaline (rod) myopathy, reducing body myopathy, sarcotubular myopathy, trilaminar fiber myopathy, zebra body myopathy, amyotonia congenita, benign congenital hypotonia, nemaline rod myopathy, myotubular myopathy, CNS disease

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Glenn Lopate, MD, Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, Washington University School of Medicine; Chief of Neurology, St Louis ConnectCare, Consulting Staff, 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, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Medical Editor

Robert Baumann, MD, Program Director, Professor, Departments of Neurology and Pediatrics, University of Kentucky
Robert Baumann, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American College of Epidemiology, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

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, and Society for Neuroscience
Disclosure: Nothing to disclose.

CME Editor

Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital
Matthew J Baker, MD is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD, Assistant Professor, Department of Pediatrics, Division of Pediatric Neurology, Department of Neurology, Oregon Health and Science University; Consulting Staff, Shriners Hospital for Children
Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.