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Duchenne muscular dystrophy (pseudohypertrophic)

Epidemiology: - most common form of muscular dystrophy Pathology: 1) cardiomyopathy 2) respiratory failure in 2nd to 3rd decade of life Genetics: 1) inheritance: X-linked, recessive 2) mutation in dystrophin gene: Xp21.2 leading to absent or diminished dystrophin protein 3) other implicated genes: CMYA5 Clinical manifestations: 1) age of onset: < 5 years 2) initial weakness in neck 3) pseudohypertrophy of calf muscles 4) weakness of trunk & proximal limb muscles; waddling gait, toe-walking, lordosis, frequent falls, difficulty in standing up & climbing up stairs 5) facial weakness occurs late 6) rate of progression is rapid 7) inability to walk by age 12 8) kyphoscoliosis 9) flexion contractures 10) mental impairment (50%) Laboratory: 1) serum creatine kinase is markedly increased 2) heel stick screening with GSP Neonatal Creatine Kinase-MM kit [6] 3) Duchenne/Becker muscular dystrophy genotyping [7] Special laboratory: electrocardiogram is abnormal Management: - supportive - oral glucocorticoids improve strength & pulmonary function - prednisone: 0.75 mg/kg/day - deflazacort 0.9 mg/kg/day - vamorolone (Agamree) FDA-approved Oct 2023 - ezutromid, a utrophin modulator, diminishes inflammation in calf muscles of children with Duchenne muscular dystrophy [5] - RNA therapy: - casimersen (Amondys 45) exon 45 skipping - eteplirsen (Exondys 51) exon 51 skipping - golodirsen (Vyondys 53) exon 53 skipping Comparative biology: - CRISPR gene editing effective in Duchenne muscular dystrophy in mice [4]

Related

Duchenne/Becker muscular dystrophy genotyping Dystrophin (DMD)

General

muscular dystrophy X-linked disease

Database Correlations

OMIM 310200

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
  2. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1038
  3. Moxley RT 3rd, Ashwal S, Pandya S, Connolly A, Florence J, Mathews K, Baumbach L, McDonald C, Sussman M, Wade C; Quality Standards Subcommittee of the American Academy of Neurology; Practice Committee of the Child Neurology Society. 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. PMID: 15642897 - Gloss D, Moxley RT 3rd, Ashwal S, Oskoui M. Practice guideline update summary: Corticosteroid treatment of Duchenne muscular dystrophy: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2016 Feb 2;86(5):465-72. PMID: 26833937
  4. Nelson CE, Hakim CH, Ousterout DG et al In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy. Science. 2016 Jan 22;351(6271):403-7 PMID: 26721684 http://science.sciencemag.org/content/351/6271/403 - Long C, Amoasii L, Mireault AA Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy. Science. 2016 Jan 22;351(6271):400-3 PMID: 26721683 Free PMC Article http://science.sciencemag.org/content/351/6271/400 - Tabebordbar M, Zhu K, Cheng JK In vivo gene editing in dystrophic mouse muscle and muscle stem cells. Science. 2016 Jan 22;351(6271):407-11 PMID: 26721686 http://science.sciencemag.org/content/351/6271/407
  5. George J, Ezutromid Shows Potential in DMD. Phase II study indicates modulating utrophin may reduce muscle inflammation. MedPage Today. April 29, 2018 https://www.medpagetoday.com/meetingcoverage/aan/72591 - Muntoni F, et al Ezutromid significantly reduced muscle damage whilst maintaining utrophin in patients with Duchenne muscular dystrophy (DMD) after 24-weeks of treatment. Anerican Academy of Neurology (AAN) 2018.
  6. FDA News Release. December 12, 2019 FDA authorizes first test to aid in newborn screening for Duchenne Muscular Dystrophy. https://www.fda.gov/news-events/press-announcements/fda-authorizes-first-test-aid-newborn-screening-duchenne-muscular-dystrophy
  7. ARUP Consult: Duchenne/Becker Muscular Dystrophy Deletion/Duplication with Reflex to Sequencing https://arupconsult.com/ati/duchenne-becker-muscular-dystrophy
  8. NEJM Knowledge+ Neurology