Jump to:

Disease/Disorder

Definition

Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD), also referred to as the dystrophinopathies, are forms of progressive muscular dystrophy associated with defects in the dystrophin gene, located at Xp21.2-21.1. They are defined by muscle degeneration, regeneration, and fibrosis. DMD is the more common and severe form with non-functional dystrophin protein molecules, and BMD is typically a milder phenotype with abnormal but partially functional dystrophin.1,2

Etiology

DMD and BMD are X-linked recessive. About 1/3 of cases result from de novo mutations in the gene. Sixty to seventy percent of mutations are deletions of one or more exons. Duplications, nonsense and missense base pair substitutions, and intronic changes may also cause disease.

Epidemiology including risk factors and primary prevention

The global prevalence of DMD is estimated to be 4.8 in 100,000 people with BMD occurring in 1.6 in 100,000 people.3 There is remarkably little variation with ethnicity. The only known risk factor is being born to a female carrier. Sons have a 50% chance of being affected, and daughters a 50% chance of being a carrier. Unless the usual X-inactivation process is highly skewed toward the X with the abnormal gene, female carriers typically have minimal if any weakness but are at risk for cardiac effects. Prenatal or pre-implantation diagnosis is possible.

Patho-anatomy/physiology

The dystrophin gene is very large at about 2.3 million base pairs, and its 79 exons code for a sequence of over 3500 amino acids. Its critical function is to create a stable connection between the skeletal muscle membrane’s dystrophin-associated complex and the actin filaments of the contractile apparatus. Without this connection, force generation breaks muscle cells which degenerate and are replaced or fibrosed. Dystrophin isoforms are also found in the brain, heart, and retina.2 

In DMD, some exonic mutations disrupt the reading frame and result in a nonsense or stop codon, thereby producing mostly truncated, non-functional molecules and less than 5% normal dystrophin protein. Other mutations permit continuous transcription but result in production of a shortened molecule, which clinically results in BMD with a milder phenotype. Point mutations may likewise result in stop codons, usually causing DMD. Exceptions occur by various mechanisms. Immunologic reaction to the abnormal dystrophin molecule and/or to revertant fibers, which express a functional protein, is thought to play a major role in DMD pathophysiology.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Presentation of DMD typically occurs in the preschool age child but can present as early as the newborn stage with hypotonia. Attainment of developmental milestones can be variable, with some having normal development and others exhibiting delays, especially in gross motor skills. Signs of mild gait abnormalities can be present as early as 3 years of age and have been confirmed on gait analysis at all stages.4 Pseudohypertrophy of the calf muscles and calf pain can also occur. Average time from appearance of first signs of DMD to diagnosis is 2.2 years and has not changed in the last twenty years.5

Boys with DMD typically gain strength during the first few years of life, but strength progressively declines resulting in changes in gait and motor function over time.6 The first muscles with noted weakness are typically the neck flexors followed by the gluteal muscles. As weakness progresses, increasing compensatory maneuvers are utilized.  A variety of standardized measures are utilized across the lifespan to monitor change including the North Star Ambulatory Assessment (NSAA) and Performance Upper Limb (PUL). Lumbar lordosis typically presents in early childhood, and Trendelenburg gait and toe walking present later. Gower’s maneuver is eventually needed to rise from the floor due to proximal muscle weakness.7,8

As boys start to enter the pre-teen and teenage years, weakness progresses. Balance becomes difficult and falls begin to occur more regularly. Ambulation is lost at a variable age, generally in the early to mid-teens, and treatment with steroids provides an additional 2-3 years of ambulation.9,10 Higher NSAA score and faster rise from the floor between 6-7 years of age is associated with older loss of ambulation.11 Clinically significant scoliosis can develop, but it is much less common in boys treated with steroids.9,10,12 Cardiac changes are common, and pulmonary function begins to decline. Eventually, trunk and arms weaken, which affects activities of daily living. If not prevented, hand contractures limit adaptive technology use though finger function typically remains into the young adult years. Eye and facial movements are also spared, but swallowing may be affected.

As boys progress to end stage disease, respiratory, cardiac, and nutritional issues become life-limiting factors. Cardiac medication, nutritional management, preventive pulmonary care, and non-invasive ventilation are required to promote survival into the 30s or longer.13-15

In BMD, the affected muscles and pattern of progression are similar, albeit with later onset and slower overall progression. Loss of ambulation varies from late teens to the third or even fourth decade of life. With milder phenotypes, lifespan may be near normal. However, those with BMD may have more significant cardiac complications.

Specific secondary or associated conditions and complications

Orthopedic complications

  • Ankle plantarflexion, knee flexion, and hip flexion contractures, as well as iliotibial band tightness develop. Toe walking is helpful to compensate for quadriceps weakness and should not be discouraged. However, it is still helpful to maintain a balanced, plantigrade foot for standing activities.8
  • Timing and degree of contracture development is variable, for unknown genetic or environmental reasons.8
  • Scoliosis is much less common with widespread use of steroids. A curve of 30 degrees or more was considered predictive of the need for spine fusion before severe decline in pulmonary function. However, this decision should be individually assessed, especially if steroids are in use, because a severe, progressive scoliosis is now unusual in patients treated with steroids and pulmonary function is better preserved through the teenage years in most cases.9,10,12,14
  • Osteopenia/osteoporosis occur even before ambulation declines. This is compounded by the effect of steroids. Fractures later in the disease course may result in the loss of ambulation. Vertebral compression fractures may cause pain and kyphosis and are screened for via routine lateral spine x-rays even if scoliosis is not clinically apparent.14

Pulmonary

  • Progressive weakness of inspiratory and expiratory muscles, with ineffective cough and reduced vital capacity.14
  • Atelectasis, pneumonia, and chronic hypoventilation starting at night, often with morning headaches and fatigue.14,15

Cardiac

  • Cardiomyopathy and conduction disturbances, which may occur in either DMD or BMD, including female carriers.14
  • Clinically evident cardiomyopathy is typically first noted after age 10, with most patients affected by age 18.14

Neurologic dystrophin expressed in brain

  • Mutation location has been found to be related to IQ scores, and reduction in average IQ score is correlated with loss of certain dystrophin isoforms (e.g., Dp140)
  • Verbal and math learning difficulties tend to predominate. This is not universal but tends to be more common in DMD compared to BMD.
  • Increased incidence of autism associated with DMD and BMD is also seen.

Essentials of Assessment

History

Family history may be negative, or there may be affected males in the maternal line, consistent with X-linked inheritance. At initial visit, the birth and early developmental history should be reviewed. Discussions regarding therapy and equipment use, leg pain or tightness, and fatigue or changes in motor function should be assessed at each visit. Rhabdomyolysis is a severe and sometimes life-threatening complication of DMD and BMD even in young children. It is prudent for the physician to ask about brown colored urine in the context of muscle pains, weakness, and vomiting at every visit. A review of the cardiac and pulmonary systems, including questions about morning headache or daytime fatigue, should also be conducted as the disease progresses.

Physical examination

Neurologic and musculoskeletal exam:

  • At the initial visit, the goal is to evaluate for features that may distinguish DMD/BMD from other neuromuscular conditions and assist with diagnosis.
    • Inspect muscles for hypertrophy, which is a common finding in DMD.
    • Palpate muscles for tenderness, which should be absent or minimal. Dermatomyositis, in contrast, involves tenderness as well as skin manifestations not seen in DMD/BMD.
    • Check deep tendon reflexes, which are typically hypoactive to absent, with down going Babinski and normal sensation.
    • Look for tongue hypertrophy.
    • Listen to heart and lungs for abnormalities such as murmur, rales, poor expansion, tachypnea, or tachycardia.
    • If question of liver disease, document lack of hepatomegaly.
    • Assess affect and verbal language skills.
  • At regular visits (every 6-12 months) the goal is to monitor changes in function and assess for comorbidities.
    • Test proximal weakness, including hip abductors and extensors in a standing position as well as neck flexors; this can be subtle early on.
    • Observe the child getting up from the floor for use of a Gower’s maneuver or other modification.
    • Assess passive range of motion (PROM).
    • Evaluate for scoliosis. For those who are unable to stand independently this should be done in a seated position.
    • If steroid-treated, look for striae and acanthosis.
    • Review speech development and behavior.

Clinical functional assessment: mobility, self-care, cognition/behavior/affective state

  • Ask about pain and falls. Observe stability of gait. Quadriceps strength of less than 3-/5 is predictive of impending loss of ambulation; gait with extreme lordosis and chin tuck for balance is an indication that walking for functional community activity is demanding and probably limiting. Use of independent transportation such as a power wheelchair is usually preferred over passive transportation or avoiding participation. However, some boys and families may be hesitant to discuss and adapt to the need for power mobility, which may foster dependency and isolation.
  • Ask about self-feeding, handwriting, computer access, and need for assistance with toileting especially as relevant to the school setting.
  • Depression, anger, moodiness, and anxiety are common. Parents may inadvertently contribute to this by withholding information and limiting communication about the muscle disease.

Laboratory studies

Creatine kinase (CK)

  • Generally, at least 10,000 and may be elevated over 30,000 in DMD. CK elevations in BMD may be slightly lower but are typically still several thousand. The CK-MM fraction is the one often elevated. High CK levels are seen from birth.
  • According to the most recent CDC care guidelines, CK should be obtained for:
    • Unexplained increase in transaminases
    • Any suspicion of abnormal muscle function in a child with family history of DMD
    • Not walking by 16-18 months, Gower’s sign present, or toe walking in a child without spasticity, regardless of family history of DMD
  • Rarely, false elevations occur due to type 1 or type 2 macro CK which are confirmed by isoenzyme assay and may be associated with autoimmunity.16
  • Milder CK elevation suggests a diagnosis other than DMD or BMD.

Liver function tests

  • Alanine transaminase (ALT) and aspartate aminotransferase (AST) may be elevated since found not only in liver but in muscle.
  • Gamma-glutamyl transferase (GGT) is more specific to the liver and should be normal; as should alkaline phosphatase, bilirubin, and coagulation (prothrombin time). Extensive workup for hepatic disease should be avoidable.

Genetic testing

  • After patient is identified as having a high CK level, testing for dystrophin gene exon deletion and duplication should occur since these comprise most mutations. If negative, gene sequencing should be performed to evaluate for other types of mutations. Should both of these be unrevealing, assessment for other genetic causes of limb-girdle muscular weakness should be undertaken.
  • Microarrays may also pick up exonic or larger deletions on Xp21 including the rare contiguous gene syndrome, which has a global early presentation including immune deficiency and other features. 

Nutritional labs

  • Vitamin D level should be monitored annually for bone health

Imaging

Muscle MRI or ultrasound can be used to differentiate the pattern of involved muscle and differentiate primary inflammatory disease from dystrophy with fatty infiltration when the diagnosis is not clear.17 Brain MRI, if done because of delays or atypical exam, will be normal, in contrast to the white matter changes observed in some of the congenital muscular dystrophies.

Spine and hip x-rays are appropriate when indicated by clinical findings. Routine spine imaging should also be obtained to monitor for asymptomatic vertebral fractures, which may be an early sign of bone fragility. The most recent CDC care guidelines prioritize these films over bone densitometry.

Supplemental assessment tools

The North Star Ambulatory Assessment (NSAA) and timed function tests, such as the 6-minute walk test (6MWT), should be performed every 6 months while patients are ambulatory to monitor clinical progression. The Performance of the Upper Limb (PUL 2.0) can be used to assess functional arm strength. Higher NSAA at baseline is associated with older age at loss of ambulation.11

Neuropsychological testing can clarify need for academic or behavioral assistance, such as section 504 plans or individualized education programs (IEPs).18

Electromyography is typically not recommended as part of diagnosis as it does not specify type of myopathy.

Biopsy can be considered if the diagnosis is in question. Muscle will be dystrophic. Immunostain will be significantly reduced or absent (0-5%) in DMD and reduced in BMD; be aware that mutations of other dystroglycan-complex proteins may cause reduction in appropriately localized dystrophin staining, and the BMD diagnosis should not be accepted without genetic confirmation.

EKG and non-invasive cardiac imaging (echocardiogram or cardiac MRI) are generally performed annually.

Serial monitoring of respiratory function with spirometry should occur at least yearly starting at 5-6 years of age, with increased frequency after loss of ambulation. Maximum inspiratory and expiratory pressures, peak cough flow, pulse oximetry, and end tidal or transcutaneous partial pressure of carbon dioxide should also be assessed in non-ambulatory patients. Sleep studies with capnography should be obtained for patients with signs or symptoms of obstructive sleep apnea or sleep-disordered breathing.14

Early predictions of outcomes

With over 7,000 known genetic mutations of the dystrophin gene and considerable variability between patients, predicting disease progression can be difficult, though specific gene abnormalities have been shown to be somewhat predictive of phenotype severity.19

Environmental

For boys with DMD, home accessibility (i.e., entrance, bathroom, bedroom, kitchen, etc.) should be assessed and, when possible, adjusted prior to decline in function. Focus should be given to acquiring vehicles suitable for power wheelchair transportation. Application for state Medicaid waiver programs may assist with modification expenses and should be considered early as waiting lists can be long.

Social role and social support system

Families affected by DMD need support in both the practical and emotional challenges inherent in a progressive, degenerative condition. Mental health needs of the patient and family should be completed at every visit. Psychology evaluation can also be helpful. The Muscular Dystrophy Association (MDA) and other support and advocacy organizations can provide resources, and professional counselors and psychologists should be utilized when needed. Although physical challenges may be less with BMD, emotional stressors may be similar. Unfounded guilt about carrying and passing on genetic disease should be addressed as well.18

Professional issues

Provide honest, not overly pessimistic information about the disease, options for treatment and care including ventilatory support and gastrostomy feeding in advanced DMD, and current state of research. Emphasize likelihood of survival into adulthood with current care and potential for extended lifespan. Encourage age-appropriate disclosure about diagnosis for children.

Rehabilitation Management and Treatments

Available or current treatment guidelines

Many sources offer guidelines for comprehensive, interdisciplinary care for those with DMD and BMD including the CDC, TREAT-NMD, and Parent Project for Muscular Dystrophy. At the time of this article, the CDC care considerations for DMD were last updated in 2018 and presented as a series of three articles in Lancet Neurology.7,18  

At different disease stages

Ambulatory

  • Initiate steroid use for DMD. Boys are generally prescribed either prednisone, prednisolone, or deflazacort (a prednisone derivative approved by the FDA for DMD in 2017 which may have a better side effect profile for weight gain and behavioral issues) in a variety of dosing regimens. Steroids should be continued across the lifespan and must not be stopped abruptly. Stress dosing of hydrocortisone for illness or major surgery should be recommended as well.7,9,10,13
  • A review of FDA-approved therapeutics should be done to determine potential eligibility based on a patient’s specific genetic mutation. At time of writing, four exon-skipping antisense oligonucleotide drugs (eteplirsen, golodirsen, casimersen, and vitolarsen) have been approved by the FDA.2,7,20,21
    • Clinical trials investigating efficacy and safety of other exon-skipping antisense oligonucleotide drugs are ongoing in the United States and Canada.22
  • Encourage regular submaximal, aerobic activity, such as swimming or biking. Limited, gentle strengthening is possible. Avoid overexertion; rarely need to limit spontaneous activity.7,23-26
  • Physical, occupational, and speech therapy as developmentally appropriate.
  • Stretching is typically recommended7; however, stretching regimens alone, aimed at prevention of contracture, have not been shown to improve joint range of motion (ROM) in DMD.8
  • Resting ankle foot orthoses (AFOs) for night use to maintain passive ROM. Do not recommend use of AFOs during ambulation, as biomechanical compensation requires slight equinus to keep line of gravity in front of the knee.7,8
  • Should the thought be that plantar flexion contractures are limiting ambulation, consider serial casting or orthopedic referral for tendon releases.8

End-stage ambulation

  • Encourage functional ambulation with transition to the use of a stander to promote bone health and maintain passive ROM as ability to ambulate is lost.7
  • Recommend power mobility equipment, transfer aids and training, and bath equipment and modifications.7
  • Continue physical, occupational, and speech therapy as indicated, generally in a consultative model to monitor PROM and update home exercise/stretching program.

Non-ambulatory

  • Independent mobility can occur with power wheelchair.
  • Continue use of resting AFOs and stander as able.7 Consider orthopedic surgery referral to consider tendon releases if plantar flexion contractures limit ability to tolerate standing program.
  • Continue physical, occupational, and speech therapy as indicated.
  • OT to evaluate for adaptations to promote the functional use of upper extremities as well as splinting for hand and wrist contracture prevention (intrinsic-plus, ulnar deviation pattern interferes with function).7
  • Consider the benefits of dynamic arm supports to improve upper extremity functional use.27
  • Preventive pulmonary and cardiac care is essential including cough assist and nighttime non-invasive ventilation.13,15 Pneumococcal and annual influenza vaccinations are strongly indicated.
  • Nutritional support should be provided, if needed.7,18

Coordination of care

Care teams for those with DMD and BMD ideally include neurology, PM&R, physical therapy, occupational therapy, cardiology, pulmonology, endocrinology, orthopedics, nutrition, psychology for both emotional and neuropsychological issues, social work, orthotics, durable medical equipment expert, and MDA or other family support and information providers.7,18

Patient & family education

Physicians should discuss mechanism of dystrophin in simple terms, rationale for physical therapy, steroid therapy, expected future needs, cognitive-behavioral effects, ideal dietary management, genetic counseling, and anesthesia precautions. Preventive, routine nature of cardiac and pulmonary screening to detect problems before serious symptoms develop and potential for treatment must be strongly emphasized.15

Measurement of treatment outcomes including those that are impairment-based, activity participation-based and environmentally-based

Impairment: Manual muscle strength testing; gait velocity and distance or NSAA/6MWT; pulmonary function tests including maximal inspiratory pressure, maximal expiratory pressure, and peak cough flow; shortening fraction and ejection fraction on echocardiogram.1

Activity: WeeFIM or PEDI appropriate

Participation/Environment: School participation, summer camp, avoidance of hospitalizations, transition and educational-vocational planning in place; The Craig Handicap Assessment and Reporting Technique (CHART) and other tools for health-related QOL may be monitored.

Translation into Practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

Encourage support group, registry, and clinical trial involvement.18

Stay abreast of new developments in therapeutic options and treatment guidelines. Insist on optimal preventive and proactive pulmonary and cardiac care, as well as management of nutrition and osteopenia/osteoporosis.

Help patients plan for longer survival into adulthood, emphasizing educational needs, inclusion and participation, and goals beyond prolonging ambulation.18

Cutting Edge/Emerging and Unique Concepts and Practice

Medical treatment for Duchenne beyond corticosteroids continues to evolve. In the last six years, four new genotype-specific, exon-skipping compounds have been approved by the FDA (eteplirsen, golodirsen, casimersen, and vitolarsen), while stop-codon readthrough with ataluren is approved in Europe. More recently, an adeno-associated virus-based gene therapy has been approved by the FDA under the accelerated approval process for use in ambulatory children ages 4-5 with DMD (delandistrogene moxeparvovec-rokl) and is currently in the process of completing a confirmatory trial. The aim of these approaches is to essentially convert the DMD phenotype to one similar to those with BMD by allowing the production of a more functional, albeit shortened, dystrophin protein. Gene editing via the CRISPR/Cas9 system is also being explored as a potential treatment option, though investigation remains in early stages. Additional genotype-independent approaches are in development and clinical trials including utrophin upregulation, phosphodiesterase inhibitors, anti-fibrosis and steroid substitutes, mini- or micro-dystrophin gene transfer via a viral vector, genome editing, and stem cells to replace lost satellite cell function. Some of these may prove useful for BMD. Compounds which mimic steroid positive effects (i.e., reduced inflammation and fibrosis) while avoiding most side effects and suppression of satellite cell function have just been approved (i.e., vamorolone) and many others are currently being researched (i.e., edasalonexent). Personalized combination therapy may become standard care.1,2,20,21,28-31

Gaps in the Evidence-Based Knowledge

The role of the immunologic system in dystrophinopathies is unclear. Viral vectors involved in gene therapy or their mini-dystrophin products may be targeted as foreign proteins, and the role of antibodies to either abnormal dystrophin molecules or to those found in revertant fibers is possibly a major mechanism of benefit from corticosteroids. 32

Several clinical trials using Adeno-Associated Virus (AAV)-Mediated Gene Therapy for dystrophin transfer have been carried out; however there are still challenges to utilization of this drug regarding efficiency, safety, and management of immune mediated response.22

Investigations regarding the safety and efficacy of exercise in individuals with DMD are ongoing. Studies have demonstrated isometric muscle contractions/exercises to be safe and improve muscle strength in patients with DMD.26 Aerobic training programs have been associated with improvements in motor function measure and 6MWT.25 Virtual reality training has been utilized to improve motor function and activities of daily living in those with DMD. However, its use in physiotherapy to improvement engagement in therapies and task performance has yet to be fully investigated.33 Additionally concrete recommendations for type, duration and amount of exercise that is safe/efficacious versus harmful is not known at this time.

References

  1. Werneck LC, Lorenzoni PJ, Ducci RD, Fustes OH, Kay CSK, Scola RH. Duchenne muscular dystrophy: an historical treatment review. Arq Neuropsiquiatr 2019;77(8):579-589. (In eng). DOI: 10.1590/0004-282×20190088.
  2. Shieh PB. Emerging Strategies in the Treatment of Duchenne Muscular Dystrophy. Neurotherapeutics 2018;15(4):840-848. (In eng). DOI: 10.1007/s13311-018-00687-z.
  3. Salari N, Fatahi B, Valipour E, et al. Global prevalence of Duchenne and Becker muscular dystrophy: a systematic review and meta-analysis. Journal of orthopaedic surgery and research 2022;17(1):1-12.
  4. Sienko S, Buckon C, Bagley A, et al. Kinematic changes in gait in boys with Duchenne Muscular Dystrophy: Utility of the Gait Deviation Index, the Gait Profile Score and the Gait Variable Scores. Gait & Posture 2023;100:157-164.
  5. Thomas S, Conway KM, Fapo O, et al. Time to diagnosis of Duchenne muscular dystrophy remains unchanged: Findings from the Muscular Dystrophy Surveillance, Tracking, and Research Network, 2000‐2015. Muscle & nerve 2022;66(2):193-197.
  6. Coratti G, Brogna C, Norcia G, et al. Longitudinal natural history in young boys with Duchenne muscular dystrophy. Neuromuscular Disorders 2019;29(11):857-862.
  7. Birnkrant DJ, Bushby K, Bann CM, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol 2018;17(3):251-267. (In eng). DOI: 10.1016/s1474-4422(18)30024-3.
  8. Nuckolls GH, Kinnett K, Dayanidhi S, et al. Conference report on contractures in musculoskeletal and neurological conditions. Muscle Nerve 2020;61(6):740-744. (In eng). DOI: 10.1002/mus.26845.
  9. Biggar WD, Harris VA, Eliasoph L, Alman B. Long-term benefits of deflazacort treatment for boys with Duchenne muscular dystrophy in their second decade. Neuromuscul Disord 2006;16(4):249-55. (In eng). DOI: 10.1016/j.nmd.2006.01.010.
  10. 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;86(5):465-72. (In eng). DOI: 10.1212/wnl.0000000000002337.
  11. Zambon AA, Ayyar Gupta V, Ridout D, et al. Peak functional ability and age at loss of ambulation in Duchenne muscular dystrophy. Developmental Medicine & Child Neurology 2022;64(8):979-988.
  12. Alman BA, Raza SN, Biggar WD. Steroid treatment and the development of scoliosis in males with duchenne muscular dystrophy. J Bone Joint Surg Am 2004;86(3):519-24. (In eng). DOI: 10.2106/00004623-200403000-00009.
  13. Silversides CK, Webb GD, Harris VA, Biggar DW. Effects of deflazacort on left ventricular function in patients with Duchenne muscular dystrophy. Am J Cardiol 2003;91(6):769-72. (In eng). DOI: 10.1016/s0002-9149(02)03429-x.
  14. 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 2018;17(4):347-361. (In eng). DOI: 10.1016/s1474-4422(18)30025-5.
  15. Eagle M, Baudouin SV, Chandler C, Giddings DR, Bullock R, Bushby K. Survival in Duchenne muscular dystrophy: improvements in life expectancy since 1967 and the impact of home nocturnal ventilation. Neuromuscul Disord 2002;12(10):926-9. (In eng). DOI: 10.1016/s0960-8966(02)00140-2.
  16. Lee KN, Csako G, Bernhardt P, Elin RJ. Relevance of macro creatine kinase type 1 and type 2 isoenzymes to laboratory and clinical data. Clin Chem 1994;40(7 Pt 1):1278-83. (In eng).
  17. Finanger EL, Russman B, Forbes SC, Rooney WD, Walter GA, Vandenborne K. Use of skeletal muscle MRI in diagnosis and monitoring disease progression in Duchenne muscular dystrophy. Phys Med Rehabil Clin N Am 2012;23(1):1-10, ix. (In eng). DOI: 10.1016/j.pmr.2011.11.004.
  18. Birnkrant DJ, Bushby K, Bann CM, et al. Diagnosis and management of Duchenne muscular dystrophy, part 3: primary care, emergency management, psychosocial care, and transitions of care across the lifespan. Lancet Neurol 2018;17(5):445-455. (In eng). DOI: 10.1016/s1474-4422(18)30026-7.
  19. Ricotti V, Ridout DA, Pane M, et al. The NorthStar Ambulatory Assessment in Duchenne muscular dystrophy: considerations for the design of clinical trials. Journal of Neurology, Neurosurgery & Psychiatry 2016;87(2):149-155.
  20. Frank DE, Schnell FJ, Akana C, et al. Increased dystrophin production with golodirsen in patients with Duchenne muscular dystrophy. Neurology 2020;94(21):e2270-e2282. (In eng). DOI: 10.1212/wnl.0000000000009233.
  21. Finkel RS, McDonald CM, Lee Sweeney H, et al. A randomized, double-blind, placebo-controlled, global phase 3 study of edasalonexent in pediatric patients with Duchenne muscular dystrophy: results of the PolarisDMD trial. Journal of neuromuscular diseases 2021;8(5):769-784.
  22. Sun C, Shen L, Zhang Z, Xie X. Therapeutic strategies for Duchenne muscular dystrophy: an update. Genes 2020;11(8):837.
  23. Alemdaroğlu I, Karaduman A, Yilmaz Ö T, Topaloğlu H. Different types of upper extremity exercise training in Duchenne muscular dystrophy: effects on functional performance, strength, endurance, and ambulation. Muscle Nerve 2015;51(5):697-705. (In eng). DOI: 10.1002/mus.24451.
  24. Jansen M, van Alfen N, Geurts AC, de Groot IJ. Assisted bicycle training delays functional deterioration in boys with Duchenne muscular dystrophy: the randomized controlled trial “no use is disuse”. Neurorehabil Neural Repair 2013;27(9):816-27. (In eng). DOI: 10.1177/1545968313496326.
  25. Bulut N, Karaduman A, Alemdaroğlu-Gürbüz İ, Yılmaz Ö, Topaloğlu H, Özçakar L. The effect of aerobic training on motor function and muscle architecture in children with Duchenne muscular dystrophy: A randomized controlled study. Clinical Rehabilitation 2022;36(8):1062-1071.
  26. Lott DJ, Taivassalo T, Cooke KD, et al. Safety, feasibility, and efficacy of strengthening exercise in Duchenne muscular dystrophy. Muscle & nerve 2021;63(3):320-326.
  27. Janssen MM, Horstik J, Klap P, de Groot IJ. Feasibility and effectiveness of a novel dynamic arm support in persons with spinal muscular atrophy and duchenne muscular dystrophy. Journal of NeuroEngineering and Rehabilitation 2021;18(1):84.
  28. Asher DR, Thapa K, Dharia SD, et al. Clinical development on the frontier: gene therapy for duchenne muscular dystrophy. Expert Opin Biol Ther 2020;20(3):263-274. (In eng). DOI: 10.1080/14712598.2020.1725469.
  29. Erkut E, Yokota T. CRISPR therapeutics for duchenne muscular dystrophy. International journal of molecular sciences 2022;23(3):1832.
  30. Hoffman EP, Schwartz BD, Mengle-Gaw LJ, et al. Vamorolone trial in Duchenne muscular dystrophy shows dose-related improvement of muscle function. Neurology 2019;93(13):e1312-e1323.
  31. Zaidman CM, Proud CM, McDonald CM, et al. Delandistrogene Moxeparvovec Gene Therapy in Ambulatory Patients (Aged≥ 4 to< 8 Years) with Duchenne Muscular Dystrophy: 1‐Year Interim Results from Study SRP‐9001‐103 (ENDEAVOR). Annals of Neurology 2023.
  32. Mendell JR, Campbell K, Rodino-Klapac L, et al. Dystrophin immunity in Duchenne’s muscular dystrophy. N Engl J Med 2010;363(15):1429-37. (In eng). DOI: 10.1056/NEJMoa1000228.
  33. Baeza-Barragán MR, Manzanares MTL, Vergara CR, Casuso-Holgado MJ, Martín-Valero R. The use of virtual reality technologies in the treatment of Duchenne muscular dystrophy: systematic review. JMIR mHealth and uHealth 2020;8(12):e21576.

Original Version of the Topic

Scott Paul, MD. Duchenne and Becker Muscular Dystrophy. 11/10/2011

Previous Revision(s) of the Topic

Vikki Stefans, MD. Duchenne and Becker Muscular Dystrophy.  4/15/2016

Caitlin Chicoine, MD, Ashlee Bolger, MD, MEd, Vikki Stefans, MD, Mary McMahon, MD. Duchenne and Becker Muscular Dystrophy. 12/22/2020

Author Disclosures

Ashlee Bolger, MD, MEd
Nothing to Disclose

Mary Craig, MD
Nothing to Disclose

Joseph Quinlan, DO
Nothing to Disclose

Vikki Stefans, MD
Sarepta, Industry-sponsored research, Unpaid – Sub-I
Edgewise, Industry-sponsored research, Unpaid – Sub-I

Mary McMahon, MD
Nothing to Disclose