Duchenne muscular dystrophy (pseudohypertrophic)
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Epidemiology
- most common form of muscular dystrophy
Pathology
- cardiomyopathy
- respiratory failure in 2nd to 3rd decade of life
Genetics
- inheritance: X-linked, recessive
- mutation in dystrophin gene: Xp21.2 leading to absent or diminished dystrophin protein
- other implicated genes: CMYA5
Clinical manifestations
- age of onset: < 5 years
- initial weakness in neck
- pseudohypertrophy of calf muscles
- weakness of trunk & proximal limb muscles; waddling gait, toe-walking, lordosis, frequent falls, difficulty in standing up & climbing up stairs
- facial weakness occurs late
- rate of progression is rapid
- inability to walk by age 12
- kyphoscoliosis
- flexion contractures
- mental impairment (50%)
Laboratory
- serum creatine kinase is markedly increased
- heel stick screening with GSP Neonatal Creatine Kinase-MM kit[6]
- Duchenne/Becker muscular dystrophy genotyping[7]
Diagnostic procedures
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]
More general terms
Additional terms
References
- ↑ Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
- ↑ Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1038
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/26833937 - ↑ 4.0 4.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26721684 <Internet> 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26721683 Free PMC Article <Internet> 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26721686 <Internet> http://science.sciencemag.org/content/351/6271/407 - ↑ 5.0 5.1 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. - ↑ 6.0 6.1 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
- ↑ 7.0 7.1 ARUP Consult: Duchenne/Becker Muscular Dystrophy Deletion/Duplication with Reflex to Sequencing https://arupconsult.com/ati/duchenne-becker-muscular-dystrophy
- ↑ NEJM Knowledge+ Neurology