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

ABSTRACT

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.