作者: Rodríguez-Gutiérrez, Eva ; Sequí-Domínguez, Irene ; Pascual-Morena, Carlos ; Martínez-Vizcaíno, Vicente ; Cavero-Redondo, Iván ; Visier-Alfonso, María Eugenia

AIMSBecker 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.METHODSA 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.RESULTSFifty-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.CONCLUSIONSThe 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.

2023-06-01·Developmental Medicine & Child Neurology

Global prevalence of intellectual developmental disorder in dystrophinopathies: A systematic review and meta‐analysis

Review

作者: Saz‐Lara, Alicia ; Álvarez‐Bueno, Celia ; Martínez‐Vizcaíno, Vicente ; Jiménez‐López, Estela ; Pascual‐Morena, Carlos ; Cavero‐Redondo, Iván ; Martínez‐García, Irene

AbstractAimTo 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.MethodSystematic 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.ResultsForty‐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+.InterpretationThere 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.

2023-03-07·Journal of Neuromuscular Diseases

Dystrophin Genotype and Risk of Neuropsychiatric Disorders in Dystrophinopathies: A Systematic Review and Meta-Analysis

Review

作者: Jiménez-López, Estela ; Pascual-Morena, Carlos ; Sequí-Domínguez, Irene ; Fernández-Bravo-Rodrigo, Jaime ; Martínez-Vizcaíno, Vicente ; Cavero-Redondo, Iván

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.

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