Background:
Duchenne muscular dystrophy (DMD) is a progressive X-linked neuromuscular disorder caused by mutations in the DMD gene, leading to dystrophin deficiency and severe muscle degeneration. The genetic heterogeneity of DMD contributes to variations in disease severity, progression, and therapeutic responses, underscoring the importance of understanding genotype-phenotype correlations to optimize patient management.
Objectives:
This systematic review explores the genetic heterogeneity of DMD by examining genotype-phenotype correlations and their implications for clinical outcomes and therapeutic strategies.
Methods: A comprehensive search of PubMed, Embase, and Cochrane Library identified studies published up to 2024 reporting on genetic mutations in the DMD gene and associated phenotypic outcomes. Data were synthesized to evaluate the relationship between specific genetic variants, disease severity, and therapeutic responses.
Results:
Analysis of 25 studies revealed that deletions in the DMD gene’s central rod domain were associated with milder phenotypes, while mutations in the N-terminal and C-terminal domains resulted in more severe functional impairments. Genotype-phenotype correlations indicated better responsiveness to exon-skipping therapies in patients with mutations amenable to skipping exons 44, 45, and 51. Variability in cardiac and respiratory involvement highlighted the influence of secondary genetic and environmental factors.
Conclusion:
Understanding the genetic heterogeneity of DMD provides critical insights into disease variability and therapeutic potential. These findings emphasize the importance of personalized approaches in DMD management and support the integration of genotype-based strategies in clinical care and research.