Key result
Mean age at loss of ambulation in Duchenne muscular dystrophy varied by genotype, ranging from 9.1 years for exon 53 skip amenability to 11.5 years for exon 8 skip amenability.
Why the study?
Duchenne muscular dystrophy causes progressive muscle weakness, loss of ambulation, and early mortality, prompting a synthesis of published data on clinical course by genotype.
Does genotype impact clinical outcomes and the natural history of disease in individuals with Duchenne muscular dystrophy?
Systematic Review
Does genotype impact clinical outcomes and the natural history of disease in individuals with Duchenne muscular dystrophy?
Genotype significantly impacts the natural history of Duchenne muscular dystrophy, particularly the age at loss of ambulation, highlighting the need to account for pathogenic variants in clinical studies.
May refine LOA counseling by genotype; extends evidence that mutation class shapes natural history and trial interpretation.
Duchenne muscular dystrophy (DMD) is associated with progressive muscle weakness, loss of ambulation (LOA), and early mortality. In this review we have synthesized published data on the clinical course of DMD by genotype. Using a systematic search implemented in Medline and Embase, 53 articles were identified that describe the clinical course of DMD, with pathogenic variants categorizable by exon skip or stop-codon readthrough amenability and outcomes presented by age. Outcomes described included those related to ambulatory, cardiac, pulmonary, or cognitive function. Estimates of the mean (95% confidence interval) age at LOA ranged from 9.1 (8.7-9.6) years among 90 patients amenable to skipping exon 53 to 11.5 (9.5-13.5) years among three patients amenable to skipping exon 8. Although function worsened with age, the impact of genotype was less clear for other outcomes (eg, forced vital capacity and left ventricular ejection fraction). Understanding the distribution of pathogenic variants is important for studies in DMD, as this research suggests major differences in the natural history of disease. In addition, specific details of the use of key medications, including corticosteroids, antisense oligonucleotides, and cardiac medications, should be reported.
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Szabo et al. (2021) conducted a systematic review in Duchenne muscular dystrophy. Genotype (exon skip or stop-codon readthrough amenability) vs. Different genotypes (e.g., exon 53 vs exon 8 skip amenability) was evaluated on Age at loss of ambulation (LOA). Mean age at loss of ambulation in Duchenne muscular dystrophy varied by genotype, ranging from 9.1 years for exon 53 skip amenability to 11.5 years for exon 8 skip amenability.
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