Becker's muscular dystrophy

Becker muscular dystrophy is an X-linked recessive inherited disorder characterized by slowly progressive muscle weakness of the legs and pelvis. It is a type of dystrophinopathy.^[1][2] This is caused by mutations in the dystrophin gene, which encodes the protein dystrophin. Becker muscular dystrophy is related to Duchenne muscular dystrophy in that both result from a mutation in the dystrophin gene.^[3]

Video explanation of Duchenne and Becker muscular dystrophy

Signs and symptoms

Some symptoms consistent with Becker's muscular dystrophy are:

Individuals with this disorder typically experience progressive muscle weakness of the leg and pelvis muscles, which is associated with a loss of muscle mass (wasting). Muscle weakness also occurs in the arms, neck, and other areas, but not as noticeably severe as in the lower half of the body.Calf muscles initially enlarge during the ages of 5-15 (an attempt by the body to compensate for loss of muscle strength), but the enlarged muscle tissue is eventually replaced by fat and connective tissue (pseudohypertrophy) as the legs become less used (with use of wheelchair).

Complications

Possible complications associated with MD are cardiac arrhythmias.^[6](BMD) Becker's muscular dystrophy also demonstrates the following:

• Mental impairment (less common in BMD than it is in DMD.)^[7]
• Pulmonary failure^[2]
• Pneumonia^[2]

Genetics

The disorder is inherited with an X-linked recessive inheritance pattern. The gene is located on the X chromosome. Since women have two X chromosomes, if one X chromosome has the non-working gene, the second X chromosome will have a working copy of the gene to compensate, because of this ability to compensate, women rarely develop symptoms. All dystrophinopathies are inherited in an X-linked recessive manner. The risk to the siblings of an affected individual depends upon the carrier status of the mother. Carrier females have a 50% chance of passing the DMD mutation in each pregnancy. Sons who inherit the mutation will be affected; daughters who inherit the mutation will be carriers. Men who have Becker muscular dystrophy can have children, and all their daughters are carriers, but none of the sons will inherit their father's mutation.^[7][8][9]

Becker muscular dystrophy occurs in approximately 1.5 to 6 in 100,000 male births, making it much less common than Duchenne muscular dystrophy. Symptoms usually appear in men at about ages 8–25, but may sometimes begin later.^[10] Genetic counseling may be advisable when potential carriers or patients want to have children. Sons of a man with Becker muscular dystrophy do not develop the disorder, but daughters will be carriers (and some carriers can experience some symptoms of muscular dystrophy), the daughters' sons may develop the disorder.^[11]

Diagnosis

Creatine kinase

In terms of the diagnosis of Becker muscular dystrophy symptom development resembles that of Duchenne muscular dystrophy. A physical exam indicates lack of pectoral and upper arm muscles, especially when the disease is unnoticed through the early teen years. Muscle wasting begins in the legs and pelvis, then progresses to the muscles of the shoulders and neck. Calf muscle enlargement (pseudohypertrophy) is quite obvious. Among the exams/tests performed are:^[12][13]

• Muscle biopsy
• Creatine kinase test
• Electromyography (shows that weakness is caused by destruction of muscle tissue rather than by damage to nerves.)
• Genetic testing

Treatment

There is no known cure for Becker muscular dystrophy yet. Treatment is aimed at control of symptoms to maximize the quality of life which can be measured by specific questionnaires.^[14] Activity is encouraged. Inactivity (such as bed rest) or sitting down for too long can worsen the muscle disease. Physical therapy may be helpful to maintain muscle strength. Orthopedic appliances such as braces and wheelchairs may improve mobility and self-care.^[8]

Immunosuppressant steroids have been known to help slow the progression of Becker's muscular dystrophy.^[15] The drug prednisone contributes to an increased production of the protein utrophin which closely resembles dystrophin, the protein that is defective in BMD.^[16]

The investigational drug Debio-025 is a known inhibitor of the protein cyclophilin D, which regulates the swelling of mitochondria in response to cellular injury. Researchers decided to test the drug in mice engineered to carry MD after earlier laboratory tests showed deleting a gene that encodes cycolphilin D reduced swelling and reversed or prevented the disease’s muscle-damaging characteristics.^[17] According to a review by Bushby, et al. if a primary protein is not functioning properly then maybe another protein could take its place by augmenting it. Upregulation of compensatory proteins has been done in models of transgenic mice.^[18]

Prognosis

The progression of Becker muscular dystrophy is highly variable—much more so than Duchenne muscular dystrophy. There is also a form that may be considered as an intermediate between Duchenne and Becker MD (mild DMD or severe BMD). Severity of the disease may be indicated by age of patient at the onset of the disease. One study showed that there may be two distinct patterns of progression in Becker muscular dystrophy. Onset at around age 7 to 8 years of age shows more cardiac involvement and trouble climbing stairs by age 20, if onset is around age 12, there is less cardiac involvement.^[12][19]

The quality of life for patients with Becker's muscular dystrophy can be impacted by the symptoms of the disorder. But with assistive devices, independence can be maintained. People affected by Becker's muscular dystrophy can still maintain active lifestyles.^[20]

History

Becker Muscular Dystrophy is named after the German doctor Peter Emil Becker (November 23, 1908 Hamburg, Germany - 2000), who published an article about it in 1955.^[21][22]

References

 This article incorporates public domain material from the Centers for Disease Control and Prevention website http://www.cdc.gov/.

Further reading

• Gaudio, Daniela del; Yang, Yaping; Boggs, Barbara A.; Schmitt, Eric S.; Lee, Jennifer A.; Sahoo, Trilochan; Pham, Hoang T.; Wiszniewska, Joanna; Craig Chinault, A. (2008-09-01). "Molecular diagnosis of Duchenne/Becker muscular dystrophy: enhanced detection of dystrophin gene rearrangements by oligonucleotide array-comparative genomic hybridization". Human Mutation. 29 (9): 1100–1107. doi:10.1002/humu.20841. ISSN 1098-1004. 
• Li, Xihua; Zhao, Lei; Zhou, Shuizhen; Hu, Chaoping; Shi, Yiyun; Shi, Wei; Li, Hui; Liu, Fang; Wu, Bingbing (2015-01-01). "A comprehensive database of Duchenne and Becker muscular dystrophy patients (0–18 years old) in East China". Orphanet Journal of Rare Diseases. 10: 5. doi:10.1186/s13023-014-0220-7. ISSN 1750-1172. PMC 4323212. PMID 25612904. 

External links

• Becker's muscular dystrophy at DMOZ