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Journal of Orthopaedic Surgery and... Feb 2022A variety of mutations in the largest human gene, dystrophin, cause a spectrum from mild to severe dystrophin-associated muscular dystrophies. Duchenne (DMD) and Becker... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A variety of mutations in the largest human gene, dystrophin, cause a spectrum from mild to severe dystrophin-associated muscular dystrophies. Duchenne (DMD) and Becker (BMD) muscular dystrophies are located at the severe end of the spectrum that primarily affects skeletal muscle. Progressive muscle weakness in these purely genetic disorders encourages families with a positive history for genetic counseling to prevent a recurrence, which requires an accurate prevalence of the disorder. Here, we provide a systematic review and meta-analysis to determine the prevalence of DMD and BMD worldwide.
METHOD
The current systematic review and meta-analysis was carried out using Cochrane seven-step procedure. After determining the research question and inclusion and exclusion criteria, the MagIran, SID, ScienceDirect, WoS, ProQuest, Medline (PubMed), Embase, Cochrane, Scopus, and Google Scholar databases were searched to find relevant studies using defined keywords and all possible keyword combinations using the AND and OR, with no time limit until 2021. The heterogeneity of studies was calculated using the I test, and the publication bias was investigated using the Begg and Mazumdar rank correlation test. Statistical analysis of data was performed using Comprehensive Meta-Analysis software (version 2).
RESULTS
A total of 25 articles involving 901,598,055 people were included. The global prevalence of muscular dystrophy was estimated at 3.6 per 100,000 people (95 CI 2.8-4.5 per 100,000 people), the largest prevalence in the Americans at 5.1 per 100,000 people (95 CI 3.4-7.8 per 100,000 people). According to the subgroup analysis, the prevalence of DMD and BMD was estimated at 4.8 per 100,000 people (95 CI 3.6-6.3 per 100,000 people) and 1.6 per 100,000 people (95 CI 1.1-2.4 per 100,000 people), respectively.
CONCLUSION
Knowing the precise prevalence of a genetic disorder helps to more accurately predict the likelihood of preventing its occurrence in families. The global prevalence of DMD and BMD was very high, indicating the urgent need for more attention to prenatal screening and genetic counseling for families with a positive history.
Topics: Dystrophin; Humans; Muscle Weakness; Muscular Dystrophies; Muscular Dystrophy, Duchenne; Mutation; Prevalence
PubMed: 35168641
DOI: 10.1186/s13018-022-02996-8 -
Orphanet Journal of Rare Diseases Jun 2020Duchenne Muscular Dystrophy (DMD) is a rare disorder caused by mutations in the dystrophin gene. A recent systematic review and meta-analysis of global DMD epidemiology... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Duchenne Muscular Dystrophy (DMD) is a rare disorder caused by mutations in the dystrophin gene. A recent systematic review and meta-analysis of global DMD epidemiology is not available. This study aimed to estimate the global overall and birth prevalence of DMD through an updated systematic review of the literature.
METHODS
MEDLINE and EMBASE databases were searched for original research articles on the epidemiology of DMD from inception until 1st October 2019. Studies were included if they were original observational research articles written in English, reporting DMD prevalence and/or incidence along with the number of individuals of the underlying population. The quality of the studies was assessed using a STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist adapted for observational studies on rare diseases. To derive the pooled epidemiological prevalence estimates, a meta-analysis was performed using random-effects logistic models for overall and birth prevalence and within two different underlying populations (i.e. all individuals and in males only), separately. Heterogeneity was assessed using Cochran's Q-test along with its derived measure of inconsistency I.
RESULTS
A total of 44 studies reporting the global epidemiology of DMD were included in the systematic review and only 40 were included in the meta-analysis. The pooled global DMD prevalence was 7.1 cases (95% CI: 5.0-10.1) per 100,000 males and 2.8 cases (95% CI: 1.6-4.6) per 100,000 in the general population, while the pooled global DMD birth prevalence was 19.8 (95% CI:16.6-23.6) per 100,000 live male births. A very high between-study heterogeneity was found for each epidemiological outcome and for all underlying populations (I > 90%). The test for funnel plot asymmetry suggested the absence of publication bias. Of the 44 studies included in this systematic review, 36 (81.8%) were assessed as being of medium and 8 (18.2%) of low quality, while no study was assessed as being of high quality.
CONCLUSIONS
Generating epidemiological evidence on DMD is fundamental to support public health decision-making. The high heterogeneity and the lack of high quality studies highlights the need to conduct better quality studies on rare diseases.
Topics: Humans; Incidence; Male; Muscular Dystrophy, Duchenne; Prevalence; Rare Diseases
PubMed: 32503598
DOI: 10.1186/s13023-020-01430-8 -
Journal of Neuromuscular Diseases 2023Dystrophinopathies are associated with neuropsychiatric disorders due to alterations in dystrophin/DMD expression. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dystrophinopathies are associated with neuropsychiatric disorders due to alterations in dystrophin/DMD expression.
OBJECTIVE
The objective was to estimate the association of developmental disorders, autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), depression, anxiety disorders, and obsessive-compulsive disorder with the dystrophin/DMD genotype in population with dystrophinopathies.
METHODS
Systematic searches of Medline, Scopus, Web of Science, and Cochrane Library were performed from inception to September 2022. We included observational studies in the population with Becker or Duchenne muscular dystrophies (BMD, DMD) that estimated the prevalence of these disorders according to Dp140 and/or Dp71 genotype. Meta-analysis of the prevalence ratio (PR) of genotype comparisons was conducted for each disorder.
RESULTS
Ten studies were included in the systematic review. In BMD, Dp140+ vs. Dp140- and Dp71+ vs. Dp71- were associated with developmental disorders with a PR of 0.11 (0.04, 0.34) and 0.22 (0.07, 0.67), respectively. In DMD, Dp140+/Dp71+ vs. Dp140- /Dp71- had a PR of 0.40 (0.28, 0.57), and Dp71+ vs. Dp71- had a PR of 0.47 (0.36, 0.63) for ADHD. However, there was no association of genotype with ASD, only a trend was observed for Dp71+ vs. Dp71-, with a PR of 0.61 (0.35, 1.06). Moreover, the data showed no association of these isoforms with emotional-related disorders.
CONCLUSIONS
In BMD, Dp140 and Dp71 could be associated with developmental disorders, while ADHD might be associated with the Dp71 genotype in DMD. Further research is needed regarding Dp140 and Dp71, especially in DMD for ASD.
Topics: Humans; Dystrophin; Genetic Predisposition to Disease; Genotype; Mental Disorders; Muscular Dystrophies; Muscular Dystrophy, Duchenne; Prevalence
PubMed: 36565132
DOI: 10.3233/JND-221586 -
Neuropathology and Applied Neurobiology Jun 2023Becker muscular dystrophy (BMD) and Duchenne muscular dystrophy (DMD) are associated with intelligence quotients (IQs) lower than the normative values, and it is... (Meta-Analysis)
Meta-Analysis Review
AIMS
Becker muscular dystrophy (BMD) and Duchenne muscular dystrophy (DMD) are associated with intelligence quotients (IQs) lower than the normative values, and it is suggested that IQ is negatively correlated with the number of affected isoforms (i.e., Dp427, Dp140 and Dp71). Therefore, the objective of this meta-analysis was to estimate the IQ, and the IQ-genotype association according to the altered dystrophin isoforms, in the population with BMD or DMD.
METHODS
A systematic search in Medline, Web of Science, Scopus and the Cochrane Library was conducted from inception to March 2023. Observational studies that determined the IQ and/or the IQ by genotype in the population with BMD or DMD were included. Meta-analyses of IQ, IQ by genotype and IQ-genotype association by comparing IQ according to the genotype were conducted. The results are shown as the mean/mean differences and 95% confidence intervals.
RESULTS
Fifty-one studies were included. The IQ in BMD was 89.92 (85.84, 94.01) and in DMD was 84.61 (82.97, 86.26). Moreover, the IQ for Dp427-/Dp140+/Dp71+ and Dp427-/Dp140-/Dp71+ was 90.62 (86.72, 94.53) and 80.73 (67.49, 93.98) in BMD, while the IQ for Dp427-/Dp140+/Dp71+, Dp427-/Dp140-/Dp71+ and Dp427-/Dp140-/Dp71- was 93.05 (89.42, 96.67), 81.78 (77.23, 86.32) and 49.19 (40.47, 57.90) in DMD. Finally, in DMD, Dp427-/Dp140-/Dp71+ vs Dp427-/Dp140+/Dp71+ and Dp427-/Dp140-/Dp71- vs Dp427-/Dp140-/Dp71+ were associated with -10.73 (-14.66, -6.81) and -36.14 (-48.87, -23.41) points, respectively.
CONCLUSIONS
The IQ in BMD and DMD was lower than the normative values. Moreover, in DMD, there is a synergistic association between the number of affected isoforms and IQ.
Topics: Humans; Dystrophin; Muscular Dystrophy, Duchenne; Protein Isoforms; Intelligence
PubMed: 37312416
DOI: 10.1111/nan.12914 -
Journal of Neurology Jul 2022Dystrophin alterations in the brain have been associated with an increased risk of epilepsy in Becker and Duchenne muscular dystrophies (BMD and DMD). Moreover, an... (Meta-Analysis)
Meta-Analysis Review
Dystrophin alterations in the brain have been associated with an increased risk of epilepsy in Becker and Duchenne muscular dystrophies (BMD and DMD). Moreover, an association between the mutation site and the risk of epilepsy is not ruled out. The aim of this systematic review and meta-analysis was to estimate the prevalence of epilepsy in BMD and DMD populations and to establish a possible association between the site of mutation in the dystrophin gene and the risk of epilepsy. Systematic searches of Medline, Scopus, Web of Science, and Cochrane Library were conducted to identify relevant studies published from inception to January 2022. Observational studies of participants with BMD/DMD estimating the prevalence of epilepsy were included. The main outcome was the prevalence of epilepsy, and the secondary outcome was the prevalence ratio considering genotype. A random effects meta-analysis was performed for the prevalence of epilepsy. Eight studies were included in the systematic review and meta-analysis. The prevalence of epilepsy was 7% (95% CI 3-11%) in BMD, 5% (95% CI 2-8%) in DMD, and 5% (95% CI 3-7%) in the overall estimate. No association was observed between mutation site and the prevalence of epilepsy. BMD/DMD is strongly associated with the prevalence of epilepsy, with a higher prevalence in BMD/DMD populations than in the general population, probably owing to alterations in Dp427. The current evidence does not support the hypothesis that Dp140 or Dp71 affect epilepsy risk.
Topics: Dystrophin; Epilepsy; Exons; Humans; Muscular Dystrophy, Duchenne; Mutation
PubMed: 35229191
DOI: 10.1007/s00415-022-11040-y -
Journal of Clinical Neuromuscular... Jun 2023The diagnosis of Duchenne and Becker muscular dystrophy (DBMD) is made by genetic testing in approximately 95% of cases. Although specific mutations can be associated...
The diagnosis of Duchenne and Becker muscular dystrophy (DBMD) is made by genetic testing in approximately 95% of cases. Although specific mutations can be associated with skeletal muscle phenotype, pulmonary and cardiac comorbidities (leading causes of death in Duchenne) have not been associated with Duchenne muscular dystrophy mutation type or location and vary within families. Therefore, identifying predictors for phenotype severity beyond frameshift prediction is important clinically. We performed a systematic review assessing research related to genotype-phenotype correlations in DBMD. While there are severity differences across the spectrum and within mild and severe forms of DBMD, few protective or exacerbating mutations within the dystrophin gene were reported. Except for intellectual disability, clinical test results reporting genotypic information are insufficient for clinical prediction of severity and comorbidities and the predictive validity is too low to be useful when advising families. Including expanded information coupled with proposed severity predictions in clinical genetic reports for DBMD is critical for improving anticipatory guidance.
Topics: Humans; Mutation; Phenotype; Genetic Testing; Muscle, Skeletal; Muscular Dystrophy, Duchenne
PubMed: 37219861
DOI: 10.1097/CND.0000000000000436 -
Developmental Medicine and Child... Jun 2023To estimate the global prevalence of intellectual developmental disorder (IDD) and the IDD prevalence-genotype association in Becker muscular dystrophy (BMD) or Duchenne... (Meta-Analysis)
Meta-Analysis Review
AIM
To estimate the global prevalence of intellectual developmental disorder (IDD) and the IDD prevalence-genotype association in Becker muscular dystrophy (BMD) or Duchenne muscular dystrophy (DMD) according to the affected isoforms of the DMD gene: Dp427, Dp140, Dp71.
METHOD
Systematic searches in MEDLINE, Scopus, Web of Science, and the Cochrane Library were conducted from inception of each database to March 2022. Observational studies that determined the prevalence of IDD in the population with BMD or DMD were included. Meta-analyses of IDD prevalence and prevalence ratios of the IDD-genotype association were conducted.
RESULTS
Forty-nine studies were included. The prevalence of IDD in BMD was 8.0% (95% confidence interval 5.0-11.0), and in DMD it was 22.0% (18.0-27.0). Meta-analyses of IDD-genotype association showed a deleterious association between IDD and the number of isoforms affected in DMD, with a prevalence ratio = 0.43 (0.28-0.64) and 0.17 (0.09-0.34) for Dp140 /Dp71 versus Dp140 /Dp71 and Dp140 /Dp71 versus Dp140 /Dp71 comparisons respectively. However, in BMD, there was no association for Dp140 /Dp71 versus Dp140 /Dp71 .
INTERPRETATION
There is a high prevalence of IDD in BMD and DMD. Moreover, the number of isoforms affected is strongly and negatively associated with the prevalence of IDD in DMD.
WHAT THIS PAPER ADDS
The global prevalence of intellectual developmental disorder (IDD) was 8% in Becker muscular dystrophy and 22% in Duchenne muscular dystrophy (DMD). The global prevalence of IDD in DMD was 12%, 29%, and 84% in participants with Dp427 /Dp140 /Dp71 , Dp427 /Dp140 /Dp71 , and Dp427 /Dp140 /Dp71 genotypes respectively. In DMD, 12% and 22% of participants had abnormal performance IQ and verbal IQ values respectively.
Topics: Child; Humans; Muscular Dystrophy, Duchenne; Dystrophin; Developmental Disabilities; Prevalence; Intellectual Disability; Protein Isoforms
PubMed: 36440509
DOI: 10.1111/dmcn.15481 -
Neuroscience and Biobehavioral Reviews Jun 2022Brain co-morbidities in DMD are well-documented, less is known about the cognitive, behavioral and psychosocial functioning of patients with BMD. (Review)
Review
BACKGROUND
Brain co-morbidities in DMD are well-documented, less is known about the cognitive, behavioral and psychosocial functioning of patients with BMD.
METHODS
The systematic review was carried out on two databases (Pubmed and Scopus) according to the PRISMA guidelines. We included all research articles specific to BMD written after 1995.
RESULTS
Studies examining neuropsychological and neurobehavioral functioning in BMD are few and have several methods limitations. BMD population is characterized by high rates of cognitive impairment, with specific involvement of different cognitive areas. Unlike DMD, verbal skills are better preserved. Neurodevelopmental and emotional/behavioral disorders have great importance in BMD, due to their high prevalence. Lack of Dp140 or Dp71 can cause intellectual disability, these isoforms are probably responsible for the other brain-related comorbidities as well.
DISCUSSION
The results suggest that cognitive and neuropsychiatric comorbid symptoms may affect a significant proportion of BMD patients therefore it is important to mental health and neuropsychological screening. Finding tools for an adequate assessment is a priority in order to include brain outcome measures in clinical trials.
Topics: Brain; Cognition; Dystrophin; Humans; Muscular Dystrophy, Duchenne; Protein Isoforms
PubMed: 35367224
DOI: 10.1016/j.neubiorev.2022.104648 -
Restorative treatments of dystrophin expression in Duchenne muscular dystrophy: A systematic review.Annals of Clinical and Translational... Sep 2020To evaluate the effect of pharmacological treatments that increase the synthesis of dystrophin in Duchenne muscular dystrophy (DMD). Systematic searches were carried out... (Meta-Analysis)
Meta-Analysis
To evaluate the effect of pharmacological treatments that increase the synthesis of dystrophin in Duchenne muscular dystrophy (DMD). Systematic searches were carried out in MEDLINE, EMBASE, and Web of Science, and in gray literature from inception to December 2019. Clinical trials addressing the effect of restorative treatments of dystrophin expression in children and adolescents with DMD on functional outcomes {(6-minute walking distance [6MWD], other timed functional tests [TFTs], The North Star Ambulatory Assessment)}, dystrophin expression, cardiorespiratory function, and biochemical tests were included. The DerSimonian-Laird method was used to calculate the pooled estimates for functional outcomes. Eleven studies were included in the systematic review and five in the meta-analysis. Eteplirsen showed a significant effect on 6MWD, Δ6MWD = 67.3 m (95% CI: 27.32, 107.28), and Δ6MWD = 151.0 m (95% CI: 36.15, 265.85) at 48 weeks and 3 years, respectively. In the systematic review, analyzing individually the clinical trials using Ataluren and Drisapersen showed a nonsignificant effect on 6MWD. However, the meta-analysis showed a significant effect on 6MWD for Ataluren and Drisapersen, Δ6MWD = 18.3 m (95% CI: 1.0, 35.5) and Δ6MWD = 21.5 m (95% CI: 4.7, 38.3), respectively. There were no significant differences according to baseline age for Drisapersen. Similarly, the meta-analysis showed effect in TFT with Ataluren. All drugs induced a partial synthesis of dystrophin, and exon skipping was obtained with Eteplirsen and Drisapersen. Eteplirsen also improved forced vital capacity (Δ%pFVC = 1.8%) and maximal inspiratory pressure (Δ%pMIP = 4.4%). Eteplirsen and Ataluren could modestly reduce disease progression. However, more trials are needed to confirm its efficacy, as well as quality of life and cost-utility studies.
Topics: Dystrophin; Humans; Morpholinos; Muscular Dystrophy, Duchenne; Oligonucleotides; Outcome Assessment, Health Care; Oxadiazoles
PubMed: 33325654
DOI: 10.1002/acn3.51149 -
Hellenic Journal of Cardiology : HJC =... 2023Duchenne muscular dystrophy is a fatal X-linked recessive disease affecting approximately 1 in 3500 births. It is characterized by a genetic lack of dystrophin, which is... (Review)
Review
Duchenne muscular dystrophy is a fatal X-linked recessive disease affecting approximately 1 in 3500 births. It is characterized by a genetic lack of dystrophin, which is an essential protein for maintaining muscle integrity. The lack of dystrophin plays a pathophysiological role in the development of dilated cardiomyopathy in Duchenne muscular dystrophy. Currently, no consensus exists on specific pharmacological therapy guidelines for these patients; however, it centers around the guidelines for heart failure management. This systematic review investigated 12 randomized control trials dating back to 2005 in the pharmacotherapy of patients with dilated cardiomyopathy Duchenne muscular dystrophy. This review specifically included angiotensin-converting enzyme inhibitors, aldosterone receptor blockers, angiotensin receptor/neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists. Despite their limitations, these studies have shown promising effects in improving the overall heart function and prognosis in patients with this condition. However, to attain higher statistical significance, future studies should investigate larger populations and for longer periods.
Topics: Humans; Cardiomyopathy, Dilated; Muscular Dystrophy, Duchenne; Dystrophin; Angiotensin-Converting Enzyme Inhibitors; Adrenergic beta-Antagonists
PubMed: 37406964
DOI: 10.1016/j.hjc.2023.06.007