Becker Muscular Dystrophy: Difference between revisions
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Becker Muscular Dystrophy is a neuromuscular disorder similar to Duchenne Muscular Dystrophy (DMD). It is caused by a genetic mutation to the ''DMD'' gene and because this gene resides on the X chromosome, the mutation is X-linked and thus primarily affects boys. It occurs less frequently than DMD (1 in 11500-19000 versus 1 in 3500-5000). Three to eight percent of female carriers present with symptoms which can be mild to rapidly progressive. | Becker Muscular Dystrophy is a neuromuscular disorder similar to Duchenne Muscular Dystrophy (DMD). It is caused by a genetic mutation to the ''DMD'' gene and because this gene resides on the X chromosome, the mutation is X-linked and thus primarily affects boys. It occurs less frequently than DMD (1 in 11500-19000 versus 1 in 3500-5000). Three to eight percent of female carriers present with symptoms which can be mild to rapidly progressive. | ||
The mutation can be spontaneous or inherited and results in abnormal production of the dystrophin protein. The ''DMD'' gene is expressed predominantly in skeletal, smooth and cardiac muscle thus an impairment in dystrophin production primarily affects these types of muscle. ( | The mutation can be spontaneous or inherited and results in abnormal production of the dystrophin protein. The ''DMD'' gene is expressed predominantly in skeletal, smooth and cardiac muscle thus an impairment in dystrophin production primarily affects these types of muscle.<ref name=":0">Wilson K, Faelan C, Patterson-Kane JC, Rudmann DG, Moore SA, Frank D, Charleston J et al. Duchenne and Becker muscular dystrophies: a review of animal models, clinical endpoints, and biomarker quantification. Toxicol Pathol. 2017 Oct; 45(7): 961–976. </ref> However, some variants of dystrophin are also expressed in the brain which might explain the cognitive impairments that can be observed with BMD and DMD.<ref name=":0" /> | ||
Cross-sections of muscle affected by DMD are “''characterized by variable degrees of atrophy, hypertrophy, myonecrosis, regeneration and endomysial fibrosis.''” | Cross-sections of muscle affected by DMD are “''characterized by variable degrees of atrophy, hypertrophy, myonecrosis, regeneration and endomysial fibrosis.''”<ref name=":0" /> Muscles affected by BMD show similar but milder changes compared to muscles of boys with DMD of the same age. Research findings suggest that dystrophin loss in combination with calcium influx (from membrane damage) and muscle contraction causes damage to muscle tissue.<ref name=":0" /> | ||
In a review by Wilson et al (2018), the authors reference Monaco et al's reading frame theory which argues that “i''f a deletion leads to a shift in the open reading frame, then premature termination results in a truncated protein (or no protein), which is often associated with the DMD phenotype (Blake ''et al.'', 2002). By contrast, if a deletion does not result in a frameshift, then a partially functional, abnormally small dystrophin protein is often produced, resulting in the BMD phenotype (Blake ''et al.'', 2002).''” Wilson et al (2018) note that although >90% of cases support this theory, some contradictory cases have been documented (e.g. milder phenotype despite out-of-frame deletions and severe phenotype despite deletions that did not disrupt the reading frame) therefore there may be additional modifiers that affect the phenotype of the disease. | In a review by Wilson et al (2018),<ref name=":0" /> the authors reference Monaco et al's reading frame theory which argues that “i''f a deletion leads to a shift in the open reading frame, then premature termination results in a truncated protein (or no protein), which is often associated with the DMD phenotype (Blake ''et al.'', 2002). By contrast, if a deletion does not result in a frameshift, then a partially functional, abnormally small dystrophin protein is often produced, resulting in the BMD phenotype (Blake ''et al.'', 2002).''” Wilson et al (2018) note that although >90% of cases support this theory, some contradictory cases have been documented (e.g. milder phenotype despite out-of-frame deletions and severe phenotype despite deletions that did not disrupt the reading frame) therefore there may be additional modifiers that affect the phenotype of the disease.<ref name=":0" /> | ||
Boys with DMD are usually diagnosed at 4 or 5 years old, are often wheelchair dependent in their early teenage years and die from cardiorespiratory complications at around 30 years old. In contrast, those with BMD experience later onset of dysfunction and diagnosis (mean onset 12 years old), remain ambulatory into their 20s, have more variable onset of cardiac issues and have longer life expectancy. | Boys with DMD are usually diagnosed at 4 or 5 years old, are often wheelchair dependent in their early teenage years and die from cardiorespiratory complications at around 30 years old. In contrast, those with BMD experience later onset of dysfunction and diagnosis (mean onset 12 years old), remain ambulatory into their 20s, have more variable onset of cardiac issues and have longer life expectancy. | ||
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Revision as of 05:09, 24 March 2021
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Becker Muscular Dystrophy is a neuromuscular disorder similar to Duchenne Muscular Dystrophy (DMD). It is caused by a genetic mutation to the DMD gene and because this gene resides on the X chromosome, the mutation is X-linked and thus primarily affects boys. It occurs less frequently than DMD (1 in 11500-19000 versus 1 in 3500-5000). Three to eight percent of female carriers present with symptoms which can be mild to rapidly progressive.
The mutation can be spontaneous or inherited and results in abnormal production of the dystrophin protein. The DMD gene is expressed predominantly in skeletal, smooth and cardiac muscle thus an impairment in dystrophin production primarily affects these types of muscle.[1] However, some variants of dystrophin are also expressed in the brain which might explain the cognitive impairments that can be observed with BMD and DMD.[1]
Cross-sections of muscle affected by DMD are “characterized by variable degrees of atrophy, hypertrophy, myonecrosis, regeneration and endomysial fibrosis.”[1] Muscles affected by BMD show similar but milder changes compared to muscles of boys with DMD of the same age. Research findings suggest that dystrophin loss in combination with calcium influx (from membrane damage) and muscle contraction causes damage to muscle tissue.[1]
In a review by Wilson et al (2018),[1] the authors reference Monaco et al's reading frame theory which argues that “if a deletion leads to a shift in the open reading frame, then premature termination results in a truncated protein (or no protein), which is often associated with the DMD phenotype (Blake et al., 2002). By contrast, if a deletion does not result in a frameshift, then a partially functional, abnormally small dystrophin protein is often produced, resulting in the BMD phenotype (Blake et al., 2002).” Wilson et al (2018) note that although >90% of cases support this theory, some contradictory cases have been documented (e.g. milder phenotype despite out-of-frame deletions and severe phenotype despite deletions that did not disrupt the reading frame) therefore there may be additional modifiers that affect the phenotype of the disease.[1]
Boys with DMD are usually diagnosed at 4 or 5 years old, are often wheelchair dependent in their early teenage years and die from cardiorespiratory complications at around 30 years old. In contrast, those with BMD experience later onset of dysfunction and diagnosis (mean onset 12 years old), remain ambulatory into their 20s, have more variable onset of cardiac issues and have longer life expectancy.
