Becker's muscular dystrophy
|Becker muscular dystrophy|
|X-linked recessive is the manner in which this condition is inherited|
|Causes||Mutations in DMD gene|
|Diagnostic method||Neurological exam, muscle exam|
|Treatment||No current cure, Physical therapy |
Becker muscular dystrophy is an X-linked recessive inherited disorder characterized by slowly progressing muscle weakness of the legs and pelvis. It is a type of dystrophinopathy. 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.
Signs and symptoms
Some symptoms consistent with Becker muscular dystrophy are:
- Muscle weakness, gradually increasing difficulty with walking
- Severe upper extremity muscle weakness
- Use of Gower's Maneuver to get up from floor
- Difficulty breathing
- Skeletal deformities of the chest, and back (scoliosis)
- Pseudohypertrophy of calf muscles
- Muscle cramps
- Heart muscle problems
- Elevated creatine kinase levels in blood
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).[medical citation needed]
Possible complications associated with muscular dystrophies (MD) are cardiac arrhythmias. Becker muscular dystrophy (BMD) also demonstrates the following:
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.
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. 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.
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:
- Muscle biopsy
- Creatine kinase test
- Electromyography (shows that weakness is caused by destruction of muscle tissue rather than by damage to nerves.)
- Genetic testing
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. 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.
Immunosuppressant steroids have been known to help slow the progression of Becker muscular dystrophy. The drug prednisone contributes to an increased production of the protein utrophin which closely resembles dystrophin, the protein that is defective in BMD.
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. 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.
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.
The quality of life for patients with Becker muscular dystrophy can be impacted by the symptoms of the disorder. But with assistive devices, independence can be maintained. People affected by Becker muscular dystrophy can still maintain active lifestyles.
- "Becker muscular dystrophy". NIH. Retrieved 17 April 2016.
- "Duchenne and Becker muscular dystrophy". NIH.gov. NIH. Retrieved 17 April 2016.
- Greco, Giovanni N. (2008). Tissue Engineering Research Trends. Nova Publishers. p. 89. ISBN 9781604562644. Retrieved 19 April 2016.
- "Becker Muscular Dystrophy Clinical Presentation: History, Physical, Causes". emedicine.medscape.com. Retrieved 2016-04-19.
- "Dystrophinopathies". www.ncbi.nlm.nih.gov. 2014-11-26. Retrieved 2016-04-19.
- Mah, Jean K.; Korngut, Lawrence; Dykeman, Jonathan; Day, Lundy; Pringsheim, Tamara; Jette, Nathalie (2014-06-01). "A systematic review and meta-analysis on the epidemiology of Duchenne and Becker muscular dystrophy". Neuromuscular Disorders. 24 (6): 482–491. doi:10.1016/j.nmd.2014.03.008. ISSN 1873-2364. PMID 24780148. – via ScienceDirect (Subscription may be required or content may be available in libraries.)
- GRIMM, TIEMO; KRESS, WOLFRAM; MENG, GERHARD; MÜLLER, CLEMENS R. (2012-12-01). "Risk assessment and genetic counseling in families with Duchenne muscular dystrophy". Acta Myologica. 31 (3): 179–183. ISSN 1128-2460. PMC . PMID 23620649.
- RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Becker muscular dystrophy". www.orpha.net. Retrieved 2016-04-19.
- Dany, Antoine; Barbe, Coralie; Rapin, Amandine; Réveillère, Christian; Hardouin, Jean-Benoit; Morrone, Isabella; Wolak-Thierry, Aurore; Dramé, Moustapha; Calmus, Arnaud; Sacconi, Sabrina; Bassez, Guillaume; Tiffreau, Vincent; Richard, Isabelle; Gallais, Benjamin; Prigent, Hélène; Taiar, Redha; Jolly, Damien; Novella, Jean-Luc; Boyer, François Constant (2015). "Construction of a Quality of Life Questionnaire for slowly progressive neuromuscular disease". Quality of Life Research. 24 (11): 2615–2623. doi:10.1007/s11136-015-1013-8. ISSN 0962-9343.
- "Duchenne/Becker Treatment and Care | Muscular Dystrophy | NCBDDD | CDC". www.cdc.gov. Retrieved 2016-04-19.
- "Dystrophinopathies Treatment & Management: Medical Care, Consultations, Activity".
- Verhaert, David; Richards, Kathryn; Rafael-Fortney, Jill A.; Raman, Subha V. (2011-01-01). "Cardiac Involvement in Patients with Muscular Dystrophies: Magnetic Resonance Imaging Phenotype and Genotypic Considerations". Circulation: Cardiovascular Imaging. 4 (1): 67–76. doi:10.1161/CIRCIMAGING.110.960740. ISSN 1941-9651. PMC . PMID 21245364.
- Reutenauer J. "Investigation of Debio 025, a cyclophilin inhibitor, in the dystrophic mdx mouse, a model for Duchenne muscular dystrophy". British Journal of Pharmacology. 155: 574–584. doi:10.1038/bjp.2008.285. PMC .
- Bushby, Kate; Lochmüller, Hanns; Lynn, Stephen; Straub, Volker (2009-12-04). "Interventions for muscular dystrophy: molecular medicines entering the clinic". The Lancet. 374 (9704): 1849–1856. doi:10.1016/S0140-6736(09)61834-1. PMID 19944865. – via ScienceDirect (Subscription may be required or content may be available in libraries.)
- Delisa, Joel A; Gans, Bruce M; Walsh, Nicholas E (2005). "Physical medicine and rehabilitation: Principles and practice": 915–16. ISBN 978-0-7817-4130-9.
- Becker PE, Kiener F (1955). "[A new x-chromosomal muscular dystrophy.]". Arch Psychiatr Nervenkr Z Gesamte Neurol Psychiatr (in German). 193 (4): 427–48. PMID 13249581.
- Becker PE (1957). "[New results of genetics of muscular dystrophy.]". Acta Genet Stat Med (in German). 7 (2): 303–10. PMID 13469170.
- 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. PMID 18752307.
- 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 . PMID 25612904.