Background
Becker muscular dystrophy (BMD), initially described by Becker and Kiener in 1955, is an inherited disease with a male distribution pattern and a clinical picture similar to that of Duchenne muscular dystrophy (DMD). [1, 2, 3, 4, 5] BMD is generally milder than DMD, however, and the onset of symptoms usually occurs later. The clinical distinction between the two 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. [6, 7, 8] Physical, occupational, speech, and recreational therapy can all play a role in the management of BMD.
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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, located on 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. [9, 10, 11, 12] Dystrophin levels in BMD are generally 30-80% of normal, while in DMD, the levels are less than 5%. [6]
A study by Zanotti et al found that in BMD, patients have “pronounced age-dependent differences in muscle pathology.” For example, capillarization was reduced in pediatric patients with BMD, while in adults with the disease, the capillary-to-fiber ratio and capillary contacts were increased; this indicated that age-related vascular adaptations to chronic muscle degeneration had occurred. Moreover, CD68-positive macrophages were predominant in younger adults, while CD4/CD8 T-cell activity was increased in older adults. [13]
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. [6, 14] This possibly explains why, in comparison with females, males suffer a rapid progression to death.
A study by Nicolas et al suggested that clinical variations in patients with BMD are related to differences in dystrophin mutations, as derived from different in-frame exon deletions. For example, delayed onset of dilated cardiomyopathy seemed to be related to specific exon deletions, as did earlier wheelchair dependency. [15]
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Etiology
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 one 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:
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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
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Mothers with germline and/or somatic mosaicism have a higher risk of transmitting the mutation
Epidemiology
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. [16] 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. [17] 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. [18]
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. [19]
A study by De Wel et al indicated that in persons with BMD, loss of ambulation leads to more rapid respiratory deterioration, with a deeper annual decline in forced vital capacity. The investigators also reported that body mass index (BMI) increase in nonambulatory patients is associated with even greater respiratory impairment. [20]
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.
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.