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Duchenne Muscular Dystrophy and Becker Muscular Dystrophy

(Duchenne's Muscular Dystrophy; Becker's Muscular Dystrophy)

By

Michael Rubin

, MDCM, New York Presbyterian Hospital-Cornell Medical Center

Reviewed/Revised Jan 2024
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Topic Resources

Duchenne muscular dystrophy and Becker muscular dystrophy are X-linked recessive X-Linked Recessive Genetic disorders determined by a single gene (Mendelian disorders) are easiest to analyze and the most well understood. If expression of a trait requires only one copy of a gene (one allele)... read more disorders characterized by progressive proximal muscle weakness caused by muscle fiber degeneration. Becker dystrophy has later onset and causes milder symptoms. Diagnosis is suggested clinically and is confirmed by genetic testing or analysis of the protein product (dystrophin) of the mutated gene. Treatment is focused on maintaining function through physical therapy and the use of braces and orthotics. Patients who have Duchenne dystrophy should be offered prednisone or deflazacort and sometimes genetic therapies.

Muscular dystrophies are inherited, progressive muscle disorders resulting from defects in one or more genes needed for normal muscle structure and function; dystrophic changes (eg, muscle fiber necrosis and regeneration) are seen on biopsy specimens.

Duchenne dystrophy and Becker dystrophy are the most prevalent muscular dystrophies. They are caused by mutations of the dystrophin gene, the largest known human gene, at the Xp21.2 locus. Up to 70% of Duchenne dystrophy is caused by a single- or multiexon deletion, approximately 10% by a duplication and 20% by a point mutation. In Becker dystrophy, approximately 70% of patients have a deletion, 20% have a duplication, and up to 10% are point mutations (1 General reference Duchenne muscular dystrophy and Becker muscular dystrophy are X-linked recessive disorders characterized by progressive proximal muscle weakness caused by muscle fiber degeneration. Becker dystrophy... read more ).

In Duchenne dystrophy, these mutations result in the severe absence (< 5%) of dystrophin, a protein in the muscle cell membrane. In Becker dystrophy, the mutations result in production of abnormal dystrophin or insufficient dystrophin.

Duchenne dystrophy and Becker dystrophy together affect about 1/5000 to 1/6000 live male births (1 General reference Duchenne muscular dystrophy and Becker muscular dystrophy are X-linked recessive disorders characterized by progressive proximal muscle weakness caused by muscle fiber degeneration. Becker dystrophy... read more ); the majority have Duchenne. Female carriers may have asymptomatic elevated creatine kinase levels and possibly calf hypertrophy.

Overview of Duchenne Muscular Dystrophy and Becker Muscular Dystrophy
VIDEO

General reference

Symptoms and Signs

Duchenne dystrophy

This disorder affects approximately 20/100,000 live male births and manifests typically between 2 and 3 years of age (1 Symptoms and signs references Duchenne muscular dystrophy and Becker muscular dystrophy are X-linked recessive disorders characterized by progressive proximal muscle weakness caused by muscle fiber degeneration. Becker dystrophy... read more ). Weakness affects proximal muscles, typically in the lower limbs initially. Children frequently toe walk and have a waddling gait and lordosis. They have difficulty running, jumping, climbing stairs, and rising from the floor. Children fall frequently, often causing arm or leg fractures (in approximately 20% of patients) (2 Symptoms and signs references Duchenne muscular dystrophy and Becker muscular dystrophy are X-linked recessive disorders characterized by progressive proximal muscle weakness caused by muscle fiber degeneration. Becker dystrophy... read more ). Progression of weakness is steady, and limb flexion contractures and scoliosis Idiopathic Scoliosis Idiopathic scoliosis is lateral curvature of the spine. Diagnosis is clinical and includes spinal x-rays. Treatment depends on the severity of the curvature. Idiopathic scoliosis is the most... read more Idiopathic Scoliosis develop in nearly all children. Firm pseudohypertrophy (fatty and fibrous replacement of certain enlarged muscle groups, notably the calves) develops. Most children need to use a wheelchair by age 12, and, if they are unsupported by mechanical ventilation, most die of respiratory complications by age 20. Children who are supported with ventilation may live an additional 10 to 20 years.

Becker dystrophy

Compared to Duchenne dystrophy, Becker dystrophy affects < 8/100,000 live male births, typically becomes symptomatic much later, and is milder (3 Symptoms and signs references Duchenne muscular dystrophy and Becker muscular dystrophy are X-linked recessive disorders characterized by progressive proximal muscle weakness caused by muscle fiber degeneration. Becker dystrophy... read more ). Ambulation is usually preserved until at least age 15, and many children remain ambulatory into adulthood. Most affected children survive into their 30s and 40s.

Symptoms and signs references

Diagnosis

  • DNA mutation analysis

  • Sometimes muscle biopsy with immunostaining analysis of dystrophin

Diagnosis is suspected by characteristic clinical findings, age at onset, and family history suggestive of X-linked recessive inheritance X-Linked Recessive Genetic disorders determined by a single gene (Mendelian disorders) are easiest to analyze and the most well understood. If expression of a trait requires only one copy of a gene (one allele)... read more . Myopathic changes are noted on electromyography (rapidly recruited, short duration, low-amplitude motor unit potentials) and, when done, muscle biopsy shows necrosis and marked variation in muscle fiber size not segregated by motor unit. Creatinine kinase levels are elevated up to 100 times normal.

Mutation analysis of DNA from peripheral blood leukocytes using multiplex ligation-dependent probe amplification (MLPA) is the primary confirmatory test; it can identify abnormalities in the dystrophin gene. If an abnormality is not detected by MLPA but Duchenne or Becker dystrophy is still suspected, full sequencing of the dystrophin gene can be done to detect small genetic changes, such as point mutations.

If genetic testing does not confirm the diagnosis, then analysis of dystrophin with immunostaining of muscle biopsy samples should be done. Dystrophin is undetectable in patients with Duchenne dystrophy. In patients with Becker dystrophy, dystrophin is typically abnormal (lower molecular weight) or present in low concentration.

Patients with Duchenne dystrophy should have a baseline assessment of cardiac function with ECG and echocardiography at the time of diagnosis or by age 6 years.

Carrier detection and prenatal diagnosis are possible by using conventional studies (eg, pedigree analysis, creatinine kinase determinations, fetal sex determination) combined with recombinant DNA analysis and dystrophin immunostaining of muscle tissue.

Treatment

  • Supportive measures

  • Sometimes corrective surgery

  • Sometimes, for cardiomyopathy, an angiotensin-converting enzyme inhibitor and/or beta-blocker

  • For Duchenne dystrophy, prednisone or deflazacort and sometimes genetic therapy

Treatment involves a multidisciplinary approach that includes both nonpharmacologic and pharmacologic measures, which include genetic therapies. Gentle (ie, submaximal) active exercise is encouraged for as long as possible to avoid disuse atrophy or complications of inactivity. Passive exercises may extend the period of ambulation. Orthopedic interventions should be aimed at maintaining function and preventing contractures. Ankle-foot orthoses worn during sleep may help prevent flexion contractures. Leg braces may temporarily help preserve ambulation or standing. Corrective surgery is sometimes needed, particularly for scoliosis. Obesity should be avoided; caloric requirements are likely to be less than normal because of decreased physical activity.

Respiratory insufficiency may be treated with noninvasive ventilatory support (eg, nasal mask Status asthmaticus ) and sometimes with mechanical ventilation. Elective tracheotomy is gaining acceptance, allowing children with Duchenne dystrophy to live into their 30s and beyond.

Investigational therapies for Duchenne dystrophy and Becker dystrophy include gene therapy, creatine, myostatin inactivation, skeletal muscle progenitors, and the antioxidant idebenone (2 Treatment references Duchenne muscular dystrophy and Becker muscular dystrophy are X-linked recessive disorders characterized by progressive proximal muscle weakness caused by muscle fiber degeneration. Becker dystrophy... read more ).

Corticosteroids for Duchenne dystrophy

In Duchenne dystrophy, daily corticosteroids (prednisone or deflazacort) are the mainstay of therapy for patients > age 4 years who are no longer gaining or have declining motor skills (3 Treatment references Duchenne muscular dystrophy and Becker muscular dystrophy are X-linked recessive disorders characterized by progressive proximal muscle weakness caused by muscle fiber degeneration. Becker dystrophy... read more ). Corticosteroids start working as early as 10 days after initiation of therapy; efficacy peaks at 3 months and persists for 6 months. Long-term use improves strength, delays the age at which ambulation is lost by 1.4 to 2.5 years, improves timed function testing (a measurement of how fast a child completes a functional task, such as walking or getting up from the floor), improves pulmonary function, reduces orthopedic complications (eg, the need for scoliosis surgery), stabilizes cardiac function (eg, delays onset of cardiomyopathy until 18 years of age), and increases survival by 5 to 15 years (3 Treatment references Duchenne muscular dystrophy and Becker muscular dystrophy are X-linked recessive disorders characterized by progressive proximal muscle weakness caused by muscle fiber degeneration. Becker dystrophy... read more ). Alternate-day prednisone is not effective. Weight gain and cushingoid facies are common adverse effects after 6 to 18 months. Risk of vertebral compression and long bone fractures also is increased.

Deflazacort may be associated with a greater risk of cataracts than prednisone.

Use of prednisone or deflazacort in Becker dystrophy has not been adequately studied.

Genetic therapy options for Duchenne dystrophy

Genetic therapies that increase dystrophin levels are available in some countries, but they are costly and their benefit is uncertain (4 Treatment references Duchenne muscular dystrophy and Becker muscular dystrophy are X-linked recessive disorders characterized by progressive proximal muscle weakness caused by muscle fiber degeneration. Becker dystrophy... read more ). The use of these therapies requires careful consideration and shared-decision making.

Exon-skipping medications (IV eteplirsen, golodirsen, viltolarsen, and casimersen) use antisense oligonucleotides that work like molecular patches to the abnormal dystrophin gene in which 1 or more exons are missing (the missing exons prevent the full protein from being assembled thus causing severe symptoms). These medications mask an exon so that it will be skipped and ignored during protein production, allowing for the production of a dystrophin protein that, although not normal, is functional and theoretically lessens symptoms so that patients function more like boys with the less severe Becker muscular dystrophy.

Stop codon read-through medications (eg, oral ataluren [PTC124]) bypass premature stop codons, allowing for the production of a functional protein. Stop codons are nonsense mutations that stop the production of a functioning protein too early, resulting in a truncated, nonfunctional protein.

Gene transfer via viral vectors (eg, delandistrogene moxeparvovec) use viral vectors to deliver corrective genetic material to the affected muscles.

Treatment references

  • 1. Birnkrant DJ, Bushby K, Bann CM, et al: Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management. Lancet Neurol 17(4):347-361, 2018. doi: 10.1016/S1474-4422(18)30025-5

  • 2. Ren S, Yao C, Liu Y, et al: Antioxidants for Treatment of Duchenne Muscular Dystrophy: A Systematic Review and Meta-Analysis. Eur Neurol 85(5):377-388, 2022. doi: 10.1159/000525045

  • 3. 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 86:465–472, 2016. doi: 10.1212/WNL.0000000000002337

  • 4. Bendicksen L, Zuckerman DM, Avorn J, et al: The Regulatory Repercussions of Approving Muscular Dystrophy Medications on the Basis of Limited Evidence. Ann Intern Med 176(9):1251-1256, 2023. doi: 10.7326/M23-1073

  • 5. Mendell JR, Goemans N, Lowes LP, et al: Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy. Ann Neurol 79(2):257-271, 2016. doi: 10.1002/ana.24555

  • 6. McDonald CM, Campbell C, Torricelli RE, et al: Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): A multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 390:(10101):1489–1498, 2017. doi: 10.1016/S0140-6736(17)31611-2

  • 7. Mendell JR, Shieh PB, McDonald CM, et al: Expression of SRP-9001 dystrophin and stabilization of motor function up to 2 years post-treatment with delandistrogene moxeparvovec gene therapy in individuals with Duchenne muscular dystrophy. Front Cell Dev Biol 11:1167762, 2023. doi: 10.3389/fcell.2023.1167762

  • 8. Elevidys. Prescribing information. Sarepta Therapeutics, Inc; 2023. Accessed January 9, 2024.

Key Points

  • Duchenne dystrophy and Becker dystrophy are X-linked recessive disorders that cause a decrease in dystrophin, a protein in muscle cell membranes.

  • Patients have significant, progressive weakness that causes severe disability, including difficulty walking, frequent falls, dilated cardiomyopathy, and early death due to respiratory insufficiency.

  • Active and passive exercise is helpful, along with leg braces and ankle-foot orthoses.

  • In Duchenne dystrophy, daily prednisone or deflazacort improves muscle strength and mass, improves pulmonary function, and helps delay onset of cardiomyopathy, although adverse effects are common.

  • For patients with Duchenne dystrophy with certain mutations, eteplirsen, golodirsen, viltolarsen, casimersen, and ataluren, despite limited evidence of clinical benefit, may be used as well.

  • An angiotensin-converting enzyme inhibitor and/or a beta-blocker may help prevent or slow progression of cardiomyopathy.

  • Ventilatory support (noninvasive and, later on, invasive) can help prolong life.

More Information

The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.

Drugs Mentioned In This Article

Drug Name Select Trade
Deltasone, Predone, RAYOS, Sterapred, Sterapred DS
Emflaza
Exondys 51
Vyondys
Viltepso
AMONDYS 45
ELEVIDYS
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