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Dystrophinopathy (DBMD) is the form of progressive muscular dystrophy associated with defects in the dystrophin gene, located at Xp21.2-21.1. Dystrophy is defined by degeneration, regeneration, and fibrosis. Duchenne is the eponym for the more common and severe form with non-functional protein molecules, and Becker for milder forms with abnormal but partially functional ones.


DBMD is X-linked recessive, with mild effects if any for most carriers. About 1/3 of cases result from new mutations in the gene. 60-65% 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

1:2500 to 1:3600 of live male births are affected by Duchenne, and the occurrence of Becker MD is about one tenth of that. 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 carriers. Carrier females with two X chromosomes, unless by chance the usual X-inactivation process is highly skewed towards the one with the abnormal gene, typically have minimal if any weakness, but are at risk for cardiac effects. Prenatal or pre-implantation diagnosis is possible. All daughters of affected males will be carriers.


The dystrophin gene is very large, at 2.5 mb; its 79 exons code for a sequence of over 3500 amino acids. Its critical function is to create a stable connection between the muscle membrane’s dystrophin-associated complex and the actin filaments of the contractile apparatus. Without this, force generation breaks muscle cells which degenerate and are replaced or fibrosed. Other domains of the protein molecule include a spectrin repeat rod connector and a nitrous oxide binding area which helps regulate microcirculation with exercise. Dystrophin isoforms are also found in brain, heart, and retina.  Some point mutations and some exon deletions allow continuity from the actin-binding N-terminal coded by the 5′ and the C-terminal coded by the 3′ end of the gene and are predicted with nearly 90% accuracy to produce a Becker phenotype by the “reading frame rule.” 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.

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

New onset/acute
Rarely, DMD presents in the newborn with hypotonia, more likely with large X-chromosome deletions in the contiguous gene syndrome. Gross motor or generalized developmental delay is typical, and gait may be abnormal from about 3 years of age. Pseudohypertrophy of calf muscles, calf pain, persistent toe walking and tight heel cords can be mistaken for cerebral palsy.

Strength is gained for the first few years of life, but gait becomes progressively affected and strength declines as assessed by manual muscle testing, first in neck flexors, then gluteals. Gower maneuver is needed to rise from the floor once proximal muscles are weakened. Hamstring, iliotibial band (ITB), and LE flexion contractures may reduce effective gait compensation.

Balance becomes difficult as quadriceps weaken; falls begin to occur. Cardiac changes may be observed. Pulmonary functions and cough peak flow begin to decline. Ambulation is lost at a variable age. Scoliosis can develop; risks are much lower if corticosteroid treated. Eventually, arm function weakens and affects ADL activity. Independent mobility depends entirely on power wheelchair. Hand contractures if left unchecked may limit adaptive technology use, though finger movements and eye and facial movements are retained. Swallowing may be affected.

Respiratory, cardiac, and nutritional issues can become life limiting factors. Cardiac medication and nutritional management, preventive pulmonary care, and non-invasive ventilation are required to promote survival into the 30s or longer.

In Becker MD, the progression and affected muscles are similar, with later onset and slower progression. Loss of ambulation varies from late teens to third or even fourth decade of life. With milder phenotypes, lifespan may be near normal.

Specific secondary or associated conditions and complications

Orthopedic complications

  • Heel cord, hamstring, and ITB tightness
  • Equinovarus and hip and knee flexion contractures can preclude standing or walking even with adequate strength.
  • Scoliosis at 20-25 or more was considered predictive of the need for spine fusion before severe decline in pulmonary function, but could be more individually assessed if steroids are in use.


  • Inspiratory and expiratory muscles gradually weaken, with ineffective cough and reduced vital capacity.
  • Atelectasis, pneumonia, and chronic hypoventilation starting at night, often with morning headaches and fatigue.


  • Cardiomyopathy and conduction disturbances possible at any age in either Becker or Duchenne.

Other Neurologic Dystrophin also expressed in brain and retina

  • Reduction in average IQ
  • Specific verbal and math learning difficulties, not universal
  • Electroretinogram changes not clinically significant



Family history may be negative, or there may be affected males in the maternal line, consistent with X-linked inheritance. Review birth and early developmental history, therapy and equipment use, leg pain or tightness, fatigue or difficulty with stair climbing or running. Sometimes an episode of rhabdomyolysis will have occurred.

Physical examination

Test proximal weakness, including hip abductors and extensors in a standing position; can be subtle early on.

Watch getting up from the floor for use of a Gower maneuver or other modification to assist LE muscles in rising.

Assess all PROM, palpate muscle for hypertrophy or tenderness (should be none or minimal in contrast to dermatomyositis, check for typical skin manifestations).

Check for scoliosis.

DTRs hypoactive to absent, Babinskis downgoing, sensation normal

General exam: tongue hypertrophy, listen to heart and lungs for extra sounds, murmur, rales, poor expansion, tachycardia/tachypnea. If question of liver disease, document lack of hepatomegaly. If steroid-treated, look for striae and acanthosis, check for cataracts via referral to ophthalmology for this purpose.

Mental status exam: affect, verbal language skills

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 mobility aids is usually preferred to passive transportation or avoiding activity and participation; some families overfocus on postponing or avoiding wheelchair use, which may foster dependency and isolation. Ask about self-feeding, handwriting and computer use, and toileting help needed especially as relevant to the school setting.  Depression, anger, moodiness, and anxiety are common. Parents may withhold information and limit communication about the muscle disease and inadvertently contribute to this.

Laboratory studies


  • at least near 10,000, may be over 30,000 in Duchenne; up to several thousand in Becker, seen from birth, primarily MM fraction
  • obtain in most boys with global developmental delays or hypotonia with weakness
  • rarely, false elevations in conditions that could be mistaken for DBMD due to type 1 or type 2 macro CPK occur, which can be addressed by isoenzyme assay
  • milder CPK elevation indicates other causes besides DBMD; differential diagnosis more complex


  • SGOT, SGPT done for other reasons are also muscle and not just liver enzymes;  GGT is more specific to liver and should be normal.

Dystrophin gene exon deletions or duplications, then sequencing, is the first step in limb-girdle presentation with high CPK. Microarrays may also pick up large deletions including Xp21.1, and may be indicated for more global early presentations, which in rare cases are part of a contiguous gene syndrome.

Nutritional labs

  • Vitamin D level; CBC, albumin, pre-albumin as clinically indicated
  • FBS or hemoglobin A1c monitoring if steroid-treated


Muscle MRI or ultrasound can be used to differentiate the pattern of involved muscle and differentiate primary inflammatory disease from dystrophy with fatty infiltration. 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.

Supplemental assessment tools

North Star Ambulatory Assessment and six minute walk test commonly used in research settings.

EKG and echocardiogram standard of care; cardiac MRI may be more sensitive to early fibrosis.

Bone densitometry baseline if steroid treatment started, fractures, or routinely around loss of ambulation, monitored every 9-18 months depending on results and clinical indications.

Neuropsychological testing for academic/behavioral help, e.g. section 504 plans or IEPs; goal is placement and grade level appropriate to cognitive, not physical function.

Electrodiagnosis if done is non-specific myopathic, +/- membrane irritability signs

Biopsy if done is dystrophic, dystrophin immunostain negative in DMD, reduced in BMD; but reduction may also be seen in other LGMDs/CMDs.

Early predictions of outcomes

Specific gene abnormalities are relatively though not entirely predictive of severity. Stop codons and out-of-frame exon deletions usually lead to truncated dystrophin molecules lacking the critical C-terminals. Exon deletions and duplications can be assessed via frame-checking utilities on the web; prediction is over 90% concordant with clinical phenotype. Some distal deletions affect brain, some proximal ones affect cardiac promoters and isoforms. Some missense mutations and in-frame deletions produce a very mild Becker phenotype. Age at diagnosis tends to be earlier for more severe phenotypes.


For DMD, plan ahead for accessibility in entrance, bath, and other parts of the home, plus 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 the practical and emotional challenges inherent in a progressive, degenerative condition. Refer to MDA and other support and advocacy organizations and use professional counselors 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 to reduce and relieve it.

Professional Issues

Provide honest, not overly pessimistic information about 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.


Available or current treatment guidelines

Many sources of guidelines for comprehensive, interdisciplinary care including the CDC, TREAT-NMD, Parent Project for Muscular Dystrophy exist. The American Academy of Neurology published a practice parameter recommending corticosteroid use for DMD in early 2005.  Should a decision be made to discontinue corticosteroids, weaning protocol should be observed.

At different disease stages

New onset/acute

  • Still no curative interventions; initiate steroid use for DMD, possibly needed to benefit from genetic therapies
  • Pain not common or severe; preserve strength, PROM, avoid overwork, rarely may need to limit spontaneous activity
  • PT, OT, ST as developmentally appropriate

Subacute, ambulatory

  • Resting AFOs for night use but not ambulation; biomechanical compensation requires slight equinus to keep weight line behind hip and ahead of knee
  • Active submaximal exercise, swimming, biking encouraged; limited, gentle strengthening is possible
  • Normalize discipline expectations, independence in ADL as able


  • Mobility aids suitable for long distance, usually power chair for DMD, transfer aids and training, bath equipment and modifications; recommend camping and adaptive sports
  • Encourage exercise/limited functional ambulation, stander use once unable
  • Adaptive utensils, upper extremity orthoses to maintain self-care independence, OT and splinting for hand and wrist contracture prevention (intrinsic-plus, ulnar deviation pattern interferes with function)
  • Consider orthopedic referral for tendon releases for positioning, shoe wear, standing, limited ambulation with KAFOs, intervention for scoliosis
  • Preventive pulmonary and cardiac care essential; cough assist, night time non-invasive ventilation slow decline; continue steroid past loss of ambulation if possible; nutritional support if needed. Flu shots strongly indicated.

Coordination of care

Team ideally includes neurology and/or PM&R, PT, OT, cardiology, pulmonology, nutrition, psychology for both emotional and neuropsychological issues, social work, DME expert, MDA or other family support and information providers, with referrals to orthopedics, orthotist, endocrinologist, ophthalmologist as appropriate.

Patient & family education

Include mechanism of dystrophin in layman’s terms, rationale for physical therapy, steroid therapy, expected future needs, cognitive-behavioral effects, ideal dietary management, genetic counseling, 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.

Measurement of Treatment Outcomes including those that are impairment-based, activity participation-based and environmentally-based

Impairment: Measure muscle strength, gait velocity and distance or North Star/6MW tests, PFT including MIP, MEP, peak cough flow, SF/EF on echocardiogram.

Activity: WeeFIM/FIM or PEDI appropriate

Participation/Environment: School participation, summer camp, avoidance of hospitalizations, transition and educational-vocational planning in place; 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

Consider the diagnosis of dystrophinopathy for any male with global delays and weakness or abnormal gait, particularly without upper motor neuron signs or a birth history predisposing to cerebral palsy.

Consider omitting biopsy and electrodiagnosis for patients with high CPK and proximal weakness in favor of molecular genetic diagnosis.

Encourage support group, registry, and clinical trial involvement.

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.


Cutting edge concepts and practice

Medical treatment for Duchenne beyond corticosteroids is on the near horizon. Genotype-specific exon-skipping compounds are nearing FDA advisory committee review in the US, and stop-codon readthrough with Ataluren is approved in Europe. Each compound is assessed individually at present and a product for exon 51 skipping which potentially benefits 13% of the population may be first. Use online resources to determine individual clinical trial and product eligibility.  These approaches essentially convert the genotype to one compatible with mild Becker MD. Additional genotype-independent approaches in development and clinical trials include utrophin upregulation, phosphodiesterase inhibitors, anti-fibrosis and steroid substitutes, and stem cells to replace lost satellite cell function. Some of these may prove useful for Becker MD. Personalized combination therapy may become standard care.


Gaps in the evidence-based knowledge

The role of the immunologic system is unclear. Mini-dystrophins or products of exon-skipping might 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. For afterload reduction, studies are underway to determine if losartan compared to lisinopril has a clinical advantage due to TGF-beta and TNF-alpha antagonist properties.

Ideal starting age for corticosteroids and use in Becker MD is unclear; alternative regimens and deflazacort versus prednisone are currently under study (FOR-DMD).


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Original Version of the Topic:

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

Author Disclosure

Vikki A. Stefans, MD
Nothing to Disclose