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Dystrophinopathies Workup

  • Author: Dinesh G Nair, MD, PhD; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE  more...
 
Updated: Apr 10, 2014
 

Laboratory Studies

Serum creatine phosphokinase (CPK), as follows:

  • This level is always increased in patients with Duchenne muscular dystrophy or Becker muscular dystrophy, probably from birth. It often is increased to levels that are 50-100 times the reference range (ie, as high as 20,000 mU/mL). In late stage DMD very little muscle mass remains to give rise to an elevated serum CPK level. Recognizing that the natural history of serum CPK in DMD is known to decrease over time, especially for longer-term clinical trials, is important.
  • A child or young adult with a CPK level within the reference range does not likely have a dystrophinopathy.
  • Strongly suspect Duchenne muscular dystrophy in a child with proximal weakness and very elevated levels of CPK. Perform further specific diagnostic testing, including DNA mutation analysis, to confirm the underlying diagnosis (see Other Tests).

There is new enthusiasm to consider newborn screening given the promise of earlier treatment with steroids, molecular therapy, or gene therapy. A 2-tiered system of analysis has been proposed that analyzes newborn CPK from dried blood spots followed up with DNA analysis from that same dried blood spot if the CPK is elevated.[6] Currently, newborn screening is not performed in the United States.

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Imaging Studies

See the list below:

  • Scoliosis frequently ensues in patients with Duchenne muscular dystrophy, particularly after they are wheelchair dependent. Radiographs of the spine are important for screening and evaluating the degree of scoliotic deformity.
  • As the disease progresses and dyspnea becomes a complaint, chest radiography is also likely to become a part of the evaluation.
  • Beyond imaging for scoliosis and dyspnea, imaging studies are of little help in making the diagnosis.
  • Imaging studies of the brain are usually unremarkable.
  • Dual energy x-ray absorptiometry is a radiographic technique to estimate bone mineral density. Individuals with dystrophinopathies can have accelerated osteopenia/osteoporosis/fracture risk, especially long-bones and vertebral compressions, due to the sedentary condition, fall risk, vitamin D deficiency, calcium intake deficiency, poor sunlight exposure, and chronic corticosteroid treatment.
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Other Tests

See the list below:

  • Electromyography
    • Electromyography (EMG), even though not diagnostic, narrows the differential diagnosis by effectively excluding primarily neurogenic processes such as spinal muscular atrophy.
    • In general, the proximal muscles of the lower extremities may exhibit the more prominent EMG findings. A sufficient number of muscles need to be sampled to establish the presence of a diffuse process such as a dystrophy. The more revealing findings will be obtained in muscles of intermediate involvement with respect to weakness.
    • The motor unit action potentials (MUAPs) in patients with Duchenne or Becker muscular dystrophy are typically of short duration, particularly the simple (ie, nonpolyphasic) MUAPs. MUAP amplitudes are variable (normal to reduced) and they are typically polyphasic from the variability in muscle fiber diameters, resulting in longer MUAP durations. Early recruitment of MUAPs may be seen. If muscle fiber loss is severe, then what appears to be a loss of motor units may be seen with fast firing individual spikes. The latter are distinguished from neurogenic processes by their generally lower-than-normal amplitudes and reduced area of spikes.
    • Fibrillation potentials and positive sharp waves, which represent spontaneously depolarizing muscle fibers bereft of nervous innervation, are encountered in active disease as necrosis engulfs the motor endplate or separates the endplate from other portions of the muscle fiber. These may be difficult to see in some muscles, requiring higher-than-usual sensitivity settings on the amplifier.
  • Molecular diagnosis
    • Individuals with Duchenne or Becker muscular dystrophy can be reliably and accurately detected from peripheral blood samples in nearly all cases. If uninformative deletion/duplication genetic tests have resulted, direct sequencing of the dystrophin gene is a viable option. Other innovative methods have been devised for accurate noninvasive diagnosis.
      • Currently, most laboratories use multiplex PCR amplification to examine deletion "hotspots," which account for approximately 59% of all mutations. This method has a 98% detection rate for deletions.
      • Duplications, which account for 5% of mutations, can be detected by several different quantitative techniques, including Southern blot, quantitative PCR, multiplex amplifiable probe hybridization (MAPH), and multiplex ligation-dependent probe (MLPA). These techniques are also highly sensitive for detecting deletions.
      • The remaining one third of the mutations are composed of subexonic sequences, of which 34% are nonsense mutations, 33% are frameshifts, 29% are splice site mutations, and 4% are missense mutations. These mutations can be screened for by using techniques such as denaturing high-performance liquid chromatography (dHPLC); single- stranded conformational polymorphism analysis with single condition amplification internal primers (SCAIP) or detection of virtually all mutations (DOVAM), a robotically enhanced multiplexed method; or denaturing gradient gel electrophoresis.
    • Recently, 96% of mutations in patients with Duchenne muscular dystrophy have been shown to be noninvasively identified by using these techniques in a 3-tiered approach. Tier 1 is PCR amplification to detect large deletions, tier 2 would use DOVAM to rapidly scan for point mutations, and tier 3 would use MAPH to define duplications. Other similar techniques can be substituted for any of the tiers. For example, MAPH can be substituted with Southern blot. This same approach can also be applied to the patient with Becker muscular dystrophy. While most of these techniques were originally used for research purposes, many are now available clinically.
    • In patients without detectable mutations of the dystrophin gene, diagnosis requires muscle biopsy for dystrophin protein quantification (see muscle biopsy in Procedures). For some families of a young boy found to have a dystrophin mutation, the muscle biopsy can provide critically important dystrophin protein information such as molecular weight size and abundance with a western blot. Immunolabeling of frozen muscle sections can enable epitope identification. This information can offer prognostic value if a predicted DNA mutation is in- or out-of-frame as some software modelling predictions and DNA sequencing techniques do indeed have a small error rate.
  • Electrocardiogram and echocardiogram
    • Electrocardiogram (ECG) provides a simple means for uncovering sinus arrhythmias and also may demonstrate deep Q waves and elevated right precordial R waves.
    • Transthoracic echocardiography yields a clearer and more dynamic view of the heart, often revealing small ventricles with prolonged diastolic relaxation.
    • A Holter monitor is valuable for paroxysmal arrhythmias.
  • Cardiac MRI and gadolinium enhancement are new noninvasive technologies that can better characterize cardiac tissue changes in dystrophinopathy and may implicate earlier treatments or prophylactic regimens to stabilize the heart.
  • Carrier detection
    • Carrier detection is an important aspect of the care and evaluation of patients with Duchenne muscular dystrophy and Becker muscular dystrophy and their family members.
    • A small minority of female carriers are symptomatic, but even in these symptomatic patients, correct diagnosis requires appropriate testing.
    • For many years, CPK testing was the best method for carrier detection; however, it is elevated in only two thirds of female carriers and the results can be difficult to interpret in ethnic and racial groups with normally elevated CPK levels. For example, African Americans have a higher reference range than whites; CPK levels of African Americans may exceed the laboratory-stated normal limits without the presence of any pathology.
    • In families in which an affected male has a known deletion or duplication of the dystrophin gene, testing for carrier status is performed accurately by testing possible carriers for the same deletion or duplication, the absence of which generally excludes them as a carrier. These methods can also be used in prenatal diagnosis but gonadal mosaicism does occur in less than 8% of women and a negative blood DNA tests can be falsely reassuring
    • If the affected males in the family are unavailable for deletion or duplication testing, the female still can be tested, but the absence of a DNA abnormality does not exclude them as carriers. Obviously, the presence of a deletion or duplication in a female always conveys carrier status.
    • In families in which the affected male has no detectable deletion or duplication, muscle immunofluorescence for dystrophin can be used in some cases. Carrier females should exhibit a mosaic pattern, with some myofibers being normal and some being abnormal. This is subject to sampling error, and again, normal biopsy findings do not exclude carrier status.
    • Unfortunately, dystrophin immunoblot quantitation, which is very useful in affected males, is not helpful in carrier detection as even female carriers manifesting the disease may have levels within the reference range.
  • If all else fails, linkage analysis comparing polymorphic DNA markers on the X chromosome of an affected patient with those of his mother or sister permits detection of asymptomatic carriers. This can be performed using PCR techniques but requires blood from at least one affected male in the family. On occasion, the results are uninformative (eg, if the mother is homozygous for all markers, discerning which X chromosome harbors the defective gene is impossible).
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Procedures

Muscle biopsy

Despite the specificity of molecular genetic diagnosis, up to 10% of boys with a clinical picture of dystrophinopathies may have no detectable deletions on DNA testing. Therefore, muscle biopsy, while supplanted as the criterion standard, remains an important adjunctive tool, both for quantifying the amount of muscle dystrophin as well as for detecting asymptomatic female carriers. Depending on the purpose of the biopsy, proper site selection is crucial.

For detection of female carriers, strong muscles may exhibit no pathology, and very weak muscles may be too devoid of fibers for adequate analysis. For affected males, a very weak muscle may have inadequate tissue for immunoblot and immunofluorescent testing. In addition, the acquisition of muscle tissue from a muscle already severely weak may precipitate further weakness. Therefore, the ideal muscle to biopsy is one that is easily accessible and exhibits moderate weakness (ie, has 80% strength).

Two methods are available for assessing dystrophin in muscle tissue.

Immunostaining of the muscle using antibodies directed against the rod domain, carboxy-terminals, and amino-terminals of dystrophin protein shows absence of the usual sarcolemmal staining in boys with Duchenne muscular dystrophy. Patients with Becker muscular dystrophy show more fragmented and patchy staining of sarcolemmal regions. See the image below.

(A) Normal dystrophin staining.(B) Intermediate dy (A) Normal dystrophin staining.(B) Intermediate dystrophin staining in a patient with Becker muscular dystrophy.(C) Absent dystrophin staining in a patient with Duchenne muscular dystrophy.

Some consider the most accurate lab method for differentiating Duchenne from Becker muscular dystrophy to be the immunoblot of muscle homogenates. Patients with Duchenne muscular dystrophy have greatly decreased or absent amounts of truncated dystrophin, whereas patients with Becker muscular dystrophy protein reveal moderately reduced amounts of dystrophin, which may be smaller (ie, deletion of the dystrophin gene) or larger (ie, duplications of the dystrophin gene) than normal. Clinical correlation is more important as there are exceptions to this notion.

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Histologic Findings

Few muscle biopsies are as instantly recognizable as those of patients with Duchenne muscular dystrophy. Features of Duchenne muscular dystrophy are reminiscent of a tissue battlefield after a major conflict, with necrotic muscle fibers littering the landscape. Widespread muscle necrosis leads to angulated fibers, central nuclei, and considerable fiber size variation, with regenerating cells in different stages of atrophy and regrowth.

Fibers that are too damaged to regenerate may become empty skeletal remnants or ghost cells. Actively regenerating fibers often display cytoplasmic basophilia, with large nuclei and prominent nucleoli. Damaged fibers exhibit reduced histochemical staining for oxidative enzymes. Initially, macrophages and cluster of differentiation 8-positive (CD8+) T lymphocytes invade necrosing muscle fibers. In time, this cellular response is supplanted by endomysial and perimysial fibrosis and fatty tissue replacement, which convey the macroscopic appearance of pseudohypertrophy.

Aside from linkage analysis, fluorescent immunostaining for dystrophin protein can be a way to diagnose carrier status in a family with no known gene deletion or duplication. Antibody staining for portions of the dystrophin molecule at the sarcolemmal membrane reveals the conspicuous absence of various portions of the dystrophin complex.

In boys with Duchenne muscular dystrophy, the sarcolemma is virtually devoid of staining (see section C in image below).

(A) Normal dystrophin staining.(B) Intermediate dy (A) Normal dystrophin staining.(B) Intermediate dystrophin staining in a patient with Becker muscular dystrophy.(C) Absent dystrophin staining in a patient with Duchenne muscular dystrophy.

In contrast, carrier females exhibit a more variable mosaic pattern consisting of normal and abnormal fibers.

Immunoblot analysis of muscle tissue, available through commercial laboratories, can determine the size and quantity of the dystrophin molecule. Patients with Duchenne muscular dystrophy exhibit no dystrophin. In patients with Becker muscular dystrophy, variable amounts of dystrophin are present but with an altered molecular size. Carriers of Duchenne muscular dystrophy exhibit mosaicism for dystrophin expression and usually have enough functional dystrophin to be within normal limits on Western blot testing, making this a generally poor method for carrier detection.

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Contributor Information and Disclosures
Author

Dinesh G Nair, MD, PhD Fellow of Clinical Neurophysiology, Department of Neurology, Rhode Island Hospital, Brown University, Providence

Dinesh G Nair, MD, PhD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Michelle L Mellion, MD Assistant Professor of Neurology, The Warren Alpert Medical School of Brown University, Rhode Island Hospital

Michelle L Mellion, MD is a member of the following medical societies: American Academy of Neurology, 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

Nicholas Lorenzo, MD, MHA, CPE Founding Editor-in-Chief, eMedicine Neurology; Founder and CEO/CMO, PHLT Consultants; Chief Medical Officer, MeMD Inc

Nicholas Lorenzo, MD, MHA, CPE is a member of the following medical societies: Alpha Omega Alpha, American Association for Physician Leadership, American Academy of Neurology

Disclosure: Nothing to disclose.

Additional Contributors

Paul E Barkhaus, MD Professor of Neurology and Physical Medicine and Rehabilitation, Department of Neurology, Medical College of Wisconsin; Section Chief, Neuromuscular and Autonomic Disorders, Department of Neurology, Director, ALS Program, Medical College of Wisconsin

Paul E Barkhaus, MD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author James M Gilchrist, MD and coauthor Brian S Tseng, MD, PhD to the development and writing of this article.

References
  1. Bushby K, Straub V. Nonmolecular treatment for muscular dystrophies. Curr Opin Neurol. 2005 Oct. 18(5):511-8. [Medline].

  2. Moxley RT 3rd, Ashwal S, Pandya S, Connolly A, Florence J, Mathews K, et al. Practice parameter: corticosteroid treatment of Duchenne dystrophy: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2005 Jan 11. 64(1):13-20. [Medline].

  3. Ervasti JM, Campbell KP. Membrane organization of the dystrophin-glycoprotein complex. Cell. 1991 Sep 20. 66(6):1121-31. [Medline].

  4. Ozawa E, Noguchi S, Mizuno Y, et al. From dystrophinopathy to sarcoglycanopathy: evolution of a concept of muscular dystrophy. Muscle Nerve. 1998 Apr. 21(4):421-38. [Medline].

  5. Darke J, Bushby K, Le Couteur A, McConachie H. Survey of behaviour problems in children with neuromuscular diseases. Eur J Paediatr Neurol. 2006 May. 10(3):129-34. [Medline].

  6. Mendell JR, Shilling C, Leslie ND et al. Evidence based path to newborn screening for Duchenne Muscular Dystrophy. Ann Neurology. 2012. 71:304–313. [Medline].

  7. Rodino-Klapac LR, Chicoine LG, Kaspar BK, Mendell JR. Gene therapy for duchenne muscular dystrophy: expectations and challenges. Arch Neurol. 2007 Sep. 64(9):1236-41. [Medline].

  8. Merlini L, Gennari M, Malaspina E et al. Early corticosteroid treatment in 4 duchenne muscular dystrophy patients: 14-year follow-up. Muscle Nerve. 2012 Jun. 45(6):796-802.

  9. American Academy of Pediatrics Section on Cardiology and Cardiac Surgery. Cardiovascular health supervision for individuals affected by Duchenne or Becker muscular dystrophy. Pediatrics. 2005 Dec. 116(6):1569-73. [Medline].

  10. Colan SD. Evolving therapeutic strategies for dystrophinopathies: potential for conflict between cardiac and skeletal needs. Circulation. 2005 Nov 1. 112(18):2756-8. [Medline].

  11. Markham LW, Kinnett K, Wong BL, Woodrow Benson D, Cripe LH. Corticosteroid treatment retards development of ventricular dysfunction in Duchenne muscular dystrophy. Neuromuscul Disord. 2008 May. 18(5):365-70. [Medline].

  12. Duboc D, Meune C, Pierre B, Wahbi K, Eymard B, Toutain A, et al. Perindopril preventive treatment on mortality in Duchenne muscular dystrophy: 10 years' follow-up. Am Heart J. 2007 Sep. 154(3):596-602. [Medline].

  13. Rhodes J, Margossian R, Darras BT et al. Safety and efficacy of carvedilol therapy for patients with dilated cardiomyopathy secondary to muscular dystrophy. Pediatr Cardiol. 2008 Mar. 29(2):343-51. [Medline].

  14. Spurney CF. Cardiomyopathy of Duchenne muscular dystrophy: current understanding and future directions. Muscle Nerve. 2011 Jul. 44(1):8-19. [Medline].

  15. Buyse GM, Goemans N, van den Hauwe M et al. Idebenone as a novel, therapeutic approach for Duchenne muscular dystrophy: results from a 12 month, double-blind, randomized placebo-controlled trial. Neuromuscul Disord. 2011 Jun. 21(6):396-405. [Medline].

  16. Quinlivan R, Roper H, Davie M, Shaw NJ, McDonagh J, Bushby K. Report of a Muscular Dystrophy Campaign funded workshop Birmingham, UK, January 16th 2004. Osteoporosis in Duchenne muscular dystrophy; its prevalence, treatment and prevention. Neuromuscul Disord. 2005 Jan. 15(1):72-9. [Medline].

  17. Apkon S, Coll J. Use of weekly alendronate to treat osteoporosis in boys with muscular dystrophy. Am J Phys Med Rehabil. 2008 Feb. 87(2):139-43. [Medline].

  18. Granchelli JA, Pollina C, Hudecki MS. Pre-clinical screening of drugs using the mdx mouse. Neuromuscul Disord. 2000 Jun. 10(4-5):235-9. [Medline].

  19. Escolar DM, Zimmerman A, Bertorini T et al. Pentoxifylline as a rescue treatment for DMD: a randomized double-blind clinical trial. Neurology. 2012 Mar. 78(12):904-13. [Medline].

  20. Kirschner J, Schessl J, Schara U, Reitter B, Stettner GM, Hobbiebrunken E, et al. Treatment of Duchenne muscular dystrophy with ciclosporin A: a randomised, double-blind, placebo-controlled multicentre trial. Lancet Neurol. 2010 Nov. 9(11):1053-9. [Medline].

  21. Bushby K, Finkel R, Birnkrant DJ et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 2010 Jan. 9(1):77-93. [Medline].

  22. Bushby K, Finkel R, Birnkrant DJ et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care. Lancet Neurol. 2010 Feb. 9(2):177-89. [Medline].

  23. Finder JD, Birnkrant D, Carl J, Farber HJ, Gozal D, Iannaccone ST, et al. Respiratory care of the patient with Duchenne muscular dystrophy: ATS consensus statement. Am J Respir Crit Care Med. 2004 Aug 15. 170(4):456-65. [Medline].

  24. Wang B, Li J, Xiao X. Adeno-associated virus vector carrying human minidystrophin genes effectively ameliorates muscular dystrophy in mdx mouse model. Proc Natl Acad Sci U S A. 2000 Dec 5. 97(25):13714-9. [Medline].

  25. Seto JT, Ramos JN, Muir L, Chamberlan JS, Odom JL. Gene Replacement Therapies for Duchenne Muscular Dystrophy Using Adeno-Associated Viral Vectors. Curr Gene Ther. 2012 Apr 25. [Epub ahead of print]:[Medline].

  26. Bowles DE, McPhee SW, Li C et al. Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vector. Mol Ther. 2012 Feb. 20(2):443-55. [Medline].

  27. Colussi C, Gaetano C, Capogrossi MC. AAV-dependent targeting of myostatin function: follistatin strikes back at muscular dystrophy. Gene Ther. 2008 Aug. 15(15):1075-6. [Medline].

  28. Fakhfakh R, Michaud A, Tremblay JP. Blocking the myostatin signal with a dominant negative receptor improves the success of human myoblast transplantation in dystrophic mice. Mol Ther. 2011 Jan. 19(1):204-10. [Medline].

  29. Fakhfakh R, Lee SJ, Tremblay JP. Administration of a soluble Activin type IIb receptor promotes the transplantation of human myoblasts in dystrophic mice. Cell Transplant. 2012 Mar 22. [Epub ahead of print]:[Medline].

  30. Markert CD, Ambrosio F, Call JA, Grange RW. Exercise and Duchenne muscular dystrophy: toward evidence-based exercise prescription. Muscle Nerve. 2011 Apr. 43(4):464-78. [Medline].

  31. Aartsma-Rus A, Bremmer-Bout M, Janson AA, et al. Targeted exon skipping as a potential gene correction therapy for Duchenne muscular dystrophy. Neuromuscul Disord. 2002 Oct. 12 Suppl 1:S71-7. [Medline].

  32. Barber BJ, Andrews JG, Lu Z, West NA, Meaney FJ, Price ET, et al. Oral corticosteroids and onset of cardiomyopathy in duchenne muscular dystrophy. J Pediatr. 2013 Oct. 163(4):1080-1084.e1. [Medline].

  33. Barkhaus PE, Gilchrist JM. Duchenne muscular dystrophy manifesting carriers. Arch Neurol. 1989 Jun. 46(6):673-5. [Medline].

  34. Beaudet A. Molecular genetics and medicine. Harrison's Principles of Internal Medicine. 12th ed. 1991. 33.

  35. Bogdanovich S, Perkins KJ, Krag TO. Therapeutics for Duchenne muscular dystrophy: current approaches and future directions. J Mol Med. 2004 Feb. 82(2):102-15. [Medline].

  36. Brooke M. Disorders of skeletal muscle. Neurology Clinical Practice. 3rd ed. 2000. 2: 2194-2198.

  37. Clemens PR, Fenwick RG, Chamberlain JS, et al. Carrier detection and prenatal diagnosis in Duchenne and Becker muscular dystrophy families, using dinucleotide repeat polymorphisms. Am J Hum Genet. 1991 Nov. 49(5):951-60. [Medline].

  38. Cossu G, Sampaolesi M. New therapies for Duchenne muscular dystrophy: challenges, prospects and clinical trials. Trends Mol Med. 2007 Dec. 13(12):520-6. [Medline].

  39. Davies KE. Challenges in Duchenne muscular dystrophy. Neuromuscul Disord. 1997 Dec. 7(8):482-6. [Medline].

  40. Dent KM, Dunn DM, von Niederhausern AC, et al. Improved molecular diagnosis of dystrophinopathies in an unselected clinical cohort. Am J Med Genet A. 2005 Apr 30. 134(3):295-8. [Medline].

  41. Duboc D, Meune C, Pierre B, Wahbi K, Eymard B, Toutain A, et al. Perindopril preventive treatment on mortality in Duchenne muscular dystrophy: 10 years' follow-up. Am Heart J. 2007 Sep. 154(3):596-602. [Medline].

  42. Engel A, Yamamoto M, Fischbeck K. Muscular dystrophies. Engel A, Franzini-Armstrong C, eds. Myology. 2nd ed. 1994. 2: 1130-1187.

  43. Gowers WR. A manual of Diseases of the Nervous System. 1888. 378-393.

  44. Harper SQ, Hauser MA, DelloRusso C, et al. Modular flexibility of dystrophin: implications for gene therapy of Duchenne muscular dystrophy. Nat Med. 2002 Mar. 8(3):253-61. [Medline].

  45. Hoffman EP, Brown RH, Kunkel LM. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell. 1987 Dec 24. 51(6):919-28. [Medline].

  46. Howard MT, Anderson CB, Fass U. Readthrough of dystrophin stop codon mutations induced by aminoglycosides. Ann Neurol. 2004 Mar. 55(3):422-6. [Medline].

  47. Matthews PM, Benjamin D, Van Bakel I, et al. Muscle X-inactivation patterns and dystrophin expression in Duchenne muscular dystrophy carriers. Neuromuscul Disord. 1995 May. 5(3):209-20. [Medline].

  48. Mendell JR, Moxley RT, Griggs RC, Brooke MH, Fenichel GM, Miller JP, et al. Randomized, double-blind six-month trial of prednisone in Duchenne's muscular dystrophy. N Engl J Med. 1989 Jun 15. 320(24):1592-7. [Medline].

  49. Pascuzzi RM. Early observations on muscular dystrophy: Gowers' textbook revisited. Semin Neurol. 1999. 19(1):87-92. [Medline].

  50. Pegoraro E, Schimke RN, Garcia C. Genetic and biochemical normalization in female carriers of Duchenne muscular dystrophy: evidence for failure of dystrophin production in dystrophin-competent myonuclei. Neurology. 1995 Apr. 45(4):677-90. [Medline].

  51. Siddique N, Sufrit R, Siddique T. Degenerative motor, sensory, and autonomic disorders. Goetz C, Pappert E eds. Textbook of Clinical Neurology. 1999. 704.

  52. Tidball JG, Wehling-Henricks M. Evolving therapeutic strategies for Duchenne muscular dystrophy: targeting downstream events. Pediatr Res. 2004 Dec. 56(6):831-41. [Medline].

  53. Wilton SD, Fletcher S. Antisense oligonucleotides in the treatment of Duchenne muscular dystrophy: Where are we now?. Neuromuscul Disord. 2005 Jun. 15(6):399-402. [Medline].

  54. Yan J, Feng J, Buzin CH. Three-tiered noninvasive diagnosis in 96% of patients with Duchenne muscular dystrophy (DMD). Hum Mutat. 2004 Feb. 23(2):203-4. [Medline].

 
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Structure of the dystroglycan complex (adapted from Ozawa et al).
The molecular organization of integral and peripheral components of the dystrophin-glycoprotein complex and novel proteins involved in muscular dystrophy in skeletal muscle.
Point vs frameshift mutations. In contrast to most point mutations, which generally preserve the reading frame, frameshift mutations often lead to truncated protein products.
Dystrophic muscle (A = Gomori trichrome; B = hematoxylin and eosin [H&E] stain).
Gowers sign.
(A) Normal dystrophin staining.(B) Intermediate dystrophin staining in a patient with Becker muscular dystrophy.(C) Absent dystrophin staining in a patient with Duchenne muscular dystrophy.
 
 
 
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