AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Becker and Kiener initially described Becker muscular dystrophy (BMD) in 1955.^{1, 2} BMD is an inherited disease with a male distribution pattern and a clinical picture similar to that of Duchenne muscular dystrophy (DMD). BMD is generally milder than DMD, and the onset of symptoms usually occurs later.

The clinical distinction between the 2 conditions is relatively easy because (1) less severe muscle weakness is observed in patients with BMD and (2) affected maternal uncles with BMD continue to be ambulatory after age 15-20 years.

Accuracy of diagnosis has been refined with the recognition of the dystrophin gene defects and with dystrophin staining of muscle biopsy specimens.^{3, 4, 5}

See also the following related eMedicine articles:
Dystrophinopathies
Muscular Dystrophy

Pathophysiology

Advancements in the diagnosis of genetic conditions have revealed that BMD is a type of recessive, X-linked dystrophinopathy. Exon deletions exist in the dystrophin gene Xp21 (X-chromosome, short arm p, region 2, band 1). Affected males in approximately 30% of known cases of BMD phenotype do not have a demonstrable mutation/deletion. A reading frame or in-frame mutation hypothesis has been proposed to explain abnormal translation of the dystrophin gene. Abnormal but functional dystrophin may be produced, in contrast to the pathology in DMD, in which a frame-shift mutation essentially leads to failure to produce dystrophin.^{6, 7, 8} Dystrophin levels in BMD are generally 30-80% of normal, while in DMD, the levels are less than 5%.³

Dilated cardiomyopathy with congestive heart failure presents in males between age 20 and 40 years, but in carrier female carriers it is found later in life.³ This possibly explains why, in comparison with females, males suffer a rapid progression to death.

See also the following related eMedicine articles:
Cardiomyopathy, Dilated [Cardiology]
Cardiomyopathy, Dilated [Emergency Medicine]
Cardiomyopathy, Dilated [Pediatrics: Cardiac Disease and Critical Care Medicine]
Cardiomyopathy, Dilated [Radiology]

Frequency

United States

The incidence and prevalence of BMD are lower than those of DMD. The estimated incidence of BMD is 1 individual per 30,000 male births, compared with 1 individual per 3500 male births for DMD.⁹ The prevalence of BMD is 17-27 cases per 1 million population.

International

The international incidence is probably similar to that in the United States.

Mortality/Morbidity

A series by Emery and Skinner showed the mean age for symptom onset to be 11 years, with the age range for onset being 2-21 years.¹⁰ The mean age at which affected patients described in the studies became nonambulatory was 27 years, with an age range of 12-30 years. Death usually resulted from respiratory or cardiac failure at a mean age of 42 years, with the age range being 23-63 years.¹¹

Ambulatory status and age may differentiate DMD from BMD. In general, an ambulatory patient who is older than 16 years may be classified as not having the Duchenne phenotype, although some subjects with BMD stop walking between ages 13-16 years. Atypical clinical presentations include cramps with exercise, focal myopathy, and isolated cardiomyopathy. Unaffected patients with no evidence of skeletal muscle disease have been classified as having subclinical BMD.¹²

Sex

BMD is an X-linked disorder. Given the transmission pattern, the disease affects primarily males. Translocations may allow the possibility of a female presentation of the BMD phenotype.

Age

The onset of symptoms occurs at a mean age of 11 years, with the age range for onset being 2-21 years.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

A typical developmental history of a patient with BMD may include the following:

• Delayed gross motor milestones (eg, late walking, running, jumping, difficulty with stair climbing) may be reported.
• Initially, some children who are later diagnosed with BMD may be called clumsy.
• Increasing numbers of falls, toe walking, and difficulty rising from the floor may be later features.
• Proximal muscle weakness is reported.
• Subclinical cases may manifest later in life; dilated cardiomyopathy can be the first sign of BMD.
• Elbow contractures may be seen later in life.

Physical

• The Gower sign is not a specific finding for muscular dystrophy, but it does point to proximal weakness in the hip extensors, leading to the pattern of movement seen when patients rise from the floor.
• A weakness pattern limited to specific muscle groups may help to differentiate BMD from other muscular dystrophies (such as limb-girdle and Emery-Dreifuss muscular dystrophies).
• Progressive, symmetrical muscle weakness and atrophy with pseudohypertrophic calves may be seen.
• Cases have been described of patients presenting without weakness but with symptoms of cardiomyopathy or cramps as the only indication of a myopathic process. Isolated weakness to the quadriceps femoris may be the only symptom noted.
• Fasciculation or sensory modality abnormalities can exclude the diagnosis of a dystrophinopathy.
• Preservation of neck flexor muscle strength may differentiate BMD from DMD.

Causes

BMD is an X-linked, recessive, inherited disorder. A family history of similarly affected maternal uncles assists the clinician in confirming a diagnosis of BMD.

• A woman is an obligate heterozygote if she has an affected son and one other affected relative in the maternal line.
• A woman with more than 1 affected child and no family history in the maternal line may have a germline mutation or a germline mosaicism.
• An isolated proband without a family history may be explained by a mutation occurring in the egg at or following conception in which only some cells were affected (mosaicism). On the other hand, the proband's mother may have inherited the gene mutation if (1) her mother was a carrier or (2) her mother or father had somatic or germline mosaicism.
• Siblings of the proband are at risk of transmitting the gene defect based on the carrier status of the mother.
• • A carrier mother has a 50% transmission rate for the mutation, per pregnancy; daughters inheriting the mutation will be carriers, and sons with the mutation will be affected.
  • Mothers with germline and/or somatic mosaicism have a higher risk of transmitting the mutation.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to Be Considered

Duchenne muscular dystrophy
Distal muscular dystrophy
Scapulohumeral dystrophy
Spinal muscular atrophy
Toxic or metabolic disorders
Spinal cord tumors
Inflammatory myopathy

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• After a thorough history has been taken and a physical examination has been performed, a diagnosis of BMD may be confirmed with the following lab study sequence:
• • Serum creatine kinase shows moderate-to-severe elevation (that is, 5-100 times the normal level).
  • Dystrophin gene deletion analysis shows specific exon deletions in about 98% of cases. Test methods include the multiplex polymerase chain reaction, southern blot analysis, and fluorescent in situ hybridization.
  • Muscle biopsy with dystrophin antibody staining demonstrates the presence of dystrophin in variable percentages. This may be helpful in the young child with no maternal history.
  • Laboratory evaluation is generally confirmatory if the patient possesses a phenotype that is consistent with muscular dystrophy and has a family history of BMD. Laboratory and phenotypic expression confirm sporadic cases. A clinical picture of muscular dystrophy, coupled with a preserved ambulatory status beyond age 16 years, is consistent with a diagnosis of BMD.
• Other laboratory studies that may be indicated include the following:
• • Liver function screen for aspartate transaminase and alanine transaminase
  • Muscle biopsy
  • Standard histology

Imaging Studies

• Spinal radiographs may be performed to follow the progression of scoliosis, particularly during adolescence.

Other Tests

• Electromyography may be indicated.
• • Expect normal nerve conduction with possible borderline-to-low motor evoked responses.
  • Expect increased insertional activity with myopathic motor unit action potentials (ie, short duration, low-to-normal amplitude, rapid recruitment, decreased units).
  • An electrodiagnostic study will facilitate a distinction between a muscular and a primary nerve process (eg, anterior horn cell disease, hereditary polyneuropathies).
  • Electromyography also may assist in identifying which muscle groups would be optimal for biopsy.
• An electrocardiogram/echocardiogram may show cardiomyopathy and/or arrhythmia. Dilated cardiomyopathy manifests after age 20 years; the risk progressively increases with age.
• Pulmonary function testing may reveal bellows failure caused by progressive weakness.
• Associated restrictive disease may be seen with scoliosis or a poorly compliant chest.

Histologic Findings

Standard muscle biopsy alone does not support a diagnosis of BMD. Histologic changes—specifically, findings of degenerating muscle fibers, a variation in fiber size, focal necrosis, regeneration, and a proliferation of connective tissue, as well as fatty replacement of degenerated muscles—point to a muscular dystrophy.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Rehabilitation Program

Physical Therapy

The role of physical therapy services is to address the functional needs of the patient as the disease progresses. Early interventions may focus on stretching tight muscles (which may initially be the only therapy goal). As the patient's weakness progresses, appropriate equipment and assistive devices will be required to enable the individual to maintain functional mobility and independence in daily living activities. Educational objectives include teaching the patient techniques for energy conservation, joint protection, and the prevention of overuse fatigue.

Occupational Therapy

Activities of daily living skills are addressed, depending on the level of impairments, in occupational therapy. Specific adaptations (to aid, for instance, dressing and bathroom skills) may be provided. Such adaptations range from methods of buttoning and zippering clothes to grab bars and raised toilet seats in the bathroom. Mobility concerns are addressed, including the need for devices to assist with mobility, such as a scooter or a fully adapted wheelchair with a custom seat and back, custom supports, and electric power.¹³

Speech Therapy

Dysphagia concerns may be evaluated by a speech therapist. Progressive weakness toward the end of the disease process may lead to dysphagia and an increased risk of aspiration pneumonia. Clinical evaluation may result in the recommendation to avoid specific food textures and liquid viscosities, as well as to avoid certain positions during feeding. Videofluoroscopic evaluation may be performed to demonstrate the risk of aspiration.

Recreational Therapy

Specific planning for avocational needs and desires may be coordinated with a recreational therapist. Resources within the community, such as activity programs with the local parks and recreation department, may be explored. Educational institutions, from public schools to community colleges and universities, may have resources that can be utilized. Adaptive physical education programs and disabled student services are generally available for qualified individuals. Access and mobility concerns in the community invariably touch upon the adjustment issues faced by individuals with a progressive disability.

Medical Issues/Complications

Potential complications of BMD include progressive weakness that results in orthopedic deformity and medical emergencies for cardiac and respiratory symptoms. Swallowing-related complications, from difficulties with mastication to problems in the pharyngeal phases, may arise with progressive weakness of the swallow mechanism. Recurrent aspiration pneumonias from progressive dysphagia may eventually cause mortality. The progressive loss of safe swallowing may result in the need for gastrostomy tube placement. Constipation may be an associated problem, given poor fluid intake and progressive difficulty with commode transfers. Overuse syndromes may lead to complaints of muscle pain, prolonged fatigue, and myoglobinuria.

Surgical Intervention

Progressive scoliosis and contracture formation may require surgical intervention. Spinal fusion to correct scoliosis may be scheduled based on the progression of spinal deformity and the age of the patient. Ankle contractures may be corrected with appropriate heel cord release and lengthening. Muscle transfers, such as with the posterior tibialis muscle, also may be considered to preserve functional mobility.

Consultations

Subspecialty consultations depend on the patient's specific needs as related to the disorder. Appropriate consultations may include the following:

• Anesthesiologist - Preoperative management and planning for appropriate anesthesia are key reasons for consultation with an anesthesiologist. The risk of malignant hyperthermia is significant, given the intrinsic muscle disorder. Appropriate cautions must be taken to avoid medications that may precipitate malignant hyperthermia.¹⁴ Dantrolene sodium is probably the best medication to use if malignant hyperthermia arises.
• Cardiologist - Cardiac function requires ongoing follow-up care. Symptomatic patients with significant cardiomyopathy have undergone transplantation procedures.
• Pulmonologist - The need for management of pulmonary problems associated with muscle weakness and restrictive disease is a typical indication. Formal pulmonary function testing may be used for preoperative care, as well as for the determination of need for ventilatory support.
• Orthopedist - The need for management of scoliosis and joint contractures are major indications for consultation with an orthopedist. The period around puberty is generally the time for significant change in scoliosis, especially if the patient's ambulatory status is limited. Heel cord release is a commonly performed joint contracture procedure.
• Geneticist - Consultation regarding the carrier status of the patient's mother and siblings is important. Transmission risk to offspring should be discussed. Identifying mosaicism in the mother or father, as well as determining the risk of transmission, is another topic to consider in nonheterozygote carrier families or in isolated cases.

Other Treatment

Because no cure exists for BMD, treatment is focused on controlling a patient's symptoms. Weakness progresses, and emergencies related to cardiac and respiratory symptoms are hallmarks of advance in the disease process. Possible future treatments for BMD include the following:

• Gene therapy may eventually lead to effective treatment, given proper identification of the gene defect and effective administration of the corrective gene to the muscle targets.¹⁵
• Myoblast treatment, as well as the use of stem cells, also may be alternative modalities if proven successful.
• Steroids have been reported to show benefit in patients with DMD, but there are conflicting reports. No definitive evidence demonstrates that steroids are effective against BMD.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

No medications are provided to patients for the specific treatment of BMD. Medications are administered to treat symptoms that are commonly are associated with BMD (such as cardiac medications for heart disease).

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• Rehabilitation management coordinates the administration of appropriate therapeutic modalities.
• • The physiatrist initiates and coordinates diagnostic studies, because muscular dystrophy may not have been diagnosed in these patients prior to the initial visit.
  • Routine health care issues include the recommendation of yearly influenza vaccinations, as well as the administration of pneumococcal vaccine.
  • Given the progressive nature of the BMD, anticipatory guidance is ongoing. The physiatrist provides recommendations for classroom accommodations and activity during a patient's school years. Work-related concerns during the patient's adult years of employment are primary issues, with work modification scenarios and the use of assistive devices being prominent concerns.
• Cardiopulmonary evaluations include pulmonary function and electrocardiographic testing.
• • Pulmonary evaluations are important in tracking the progression of muscular weakness affecting ventilation.
  • A simple clinical test with a spirometer may be employed to measure maximal expiratory volume during routine clinic visits.
  • A pattern of falling maximal expiratory volumes over time may indicates the need for formal pulmonary function to determine the need for ventilatory support.
  • Nighttime ventilatory support with a mask or nasal bilevel positive airway pressure is commonly used if a rising pCO₂ is noted. The results from sleep studies also may suggest progressive difficulty in nighttime ventilation.
  • Cardiovascular health supervision guidelines are available⁹

Deterrence

• Prenatal diagnosis is available for a woman with an at-risk pregnancy who has been identified as having a family history of muscular dystrophy. Identification of dystrophin gene exon deletions in a male fetus points to the risk of a child with muscular dystrophy. Couples may elect to terminate the pregnancy if the fetus is affected.
• Carrier status may be determined in the mother and siblings of a proband.

Complications

• Progressive disability
• Dilated cardiomyopathy
• Respiratory symptoms, with a potential need for ventilatory support
• Joint contractures
• Scoliosis
• Dysphagia
• Functional constipation

Prognosis

• See Mortality/Morbidity.

Patient Education

• Well in advance of the projected necessity, discuss the decision, with the occurrence of pulmonary failure, to place a tracheostomy tube for positive-pressure ventilation, as well as for airway and secretion management. Inform the patient, family members, and/or caregivers of the implications of placing the patient on a ventilator. Early education can help the patient and his/her family to determine advanced directives.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Pitfalls include a failure to advise at-risk parents and family members about BMD or to not offer evaluation by a geneticist. Disclose transmission risks, recurrence risks, and options if a prenatal diagnosis is performed.

Special Concerns

• Be aware of the high risk of malignant hyperthermia that is associated with certain anesthetic agents. Consultation with an anesthesiologist is recommended prior to surgical procedures requiring anesthesia.
• Dilated cardiomyopathy may be the initial presentation of BMD.
• Because nonsteroidal anti-inflammatory medications can potentially worsen cardiac function, caution should be exercised with regard to their use.¹⁶

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Becker PE, Kiener F. [A new x-chromosomal muscular dystrophy.]. Arch Psychiatr Nervenkr Z Gesamte Neurol Psychiatr. 1955;193(4):427-48. [Medline].
2. Becker PE. Two families of benign sex-linked recessive muscular dystrophy. Rev Can Biol. Sep-Dec 1962;21:551-66. [Medline].
3. Angelini C, Fanin M, Pegoraro E, et al. Clinical-molecular correlation in 104 mild X-linked muscular dystrophy patients: characterization of sub-clinical phenotypes. Neuromuscul Disord. Jul 1994;4(4):349-58. [Medline].
4. Gurvich OL, Tuohy TM, Howard MT, et al. DMD pseudoexon mutations: splicing efficiency, phenotype, and potential therapy. Ann Neurol. Jan 2008;63(1):81-9. [Medline].
5. Ashton EJ, Yau SC, Deans ZC, et al. Simultaneous mutation scanning for gross deletions, duplications and point mutations in the DMD gene. Eur J Hum Genet. Jan 2008;16(1):53-61. [Medline].
6. Arahata K, Beggs AH, Honda H, et al. Preservation of the C-terminus of dystrophin molecule in the skeletal muscle from Becker muscular dystrophy. J Neurol Sci. Feb 1991;101(2):148-56. [Medline].
7. Koenig M, Beggs AH, Moyer M, et al. The molecular basis for Duchenne versus Becker muscular dystrophy: correlation of severity with type of deletion. Am J Hum Genet. Oct 1989;45(4):498-506. [Medline]. [Full Text].
8. Schwartz M, Hertz JM, Sveen ML, et al. LGMD2I presenting with a characteristic Duchenne or Becker muscular dystrophy phenotype. Neurology. May 10 2005;64(9):1635-7. [Medline].
9. Cardiovascular health supervision for individuals affected by Duchenne or Becker muscular dystrophy. Pediatrics. Dec 2005;116(6):1569-73. [Medline]. [Full Text].
10. Emery AE, Skinner R. Clinical studies in benign (Becker type) X-linked muscular dystrophy. Clin Genet. Oct 1976;10(4):189-201. [Medline].
11. Holloway SM, Wilcox DE, Wilcox A, et al. Life expectancy and death from cardiomyopathy amongst carriers of Duchenne and Becker muscular dystrophy in Scotland. Heart. Oct 11 2007;[Medline].
12. Young HK, Barton BA, Waisbren S, et al. Cognitive and Psychological Profile of Males With Becker Muscular Dystrophy. J Child Neurol. Dec 3 2007;[Medline].
13. Grootenhuis MA, de Boone J, van der Kooi AJ. Living with muscular dystrophy: health related quality of life consequences for children and adults. Health Qual Life Outcomes. 2007;5:31. [Medline]. [Full Text].
14. Hayes J, Veyckemans F, Bissonnette B. Duchenne muscular dystrophy: an old anesthesia problem revisited. Paediatr Anaesth. Feb 2008;18(2):100-6. [Medline].
15. Duan D. Myodys, a full-length dystrophin plasmid vector for Duchenne and Becker muscular dystrophy gene therapy. Curr Opin Mol Ther. Feb 2008;10(1):86-94. [Medline].
16. Stöllberger C, Finsterer J. Worsening of heart failure in Becker muscular dystrophy after nonsteroidal anti-inflammatory drugs. South Med J. Apr 2005;98(4):478-80. [Medline].

Article Last Updated: Apr 18, 2008