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. 2024 Nov;70(5):1053-1061.
doi: 10.1002/mus.28255. Epub 2024 Sep 18.

The impact of genotype on age at loss of ambulation in individuals with Duchenne muscular dystrophy treated with corticosteroids: A single-center study of 555 patients

Alexander Zygmunt  1   2 , Brenda Wong  3 , David Moon  4 , Paul Horn  1   2 , Richard Rathbun  1 , Joshua Lambert  5 , Jean Bange  1 , Irina Rybalsky  1 , Lisa Reebals  1 , Cuixia Tian  1   2
Affiliations

The impact of genotype on age at loss of ambulation in individuals with Duchenne muscular dystrophy treated with corticosteroids: A single-center study of 555 patients

Alexander Zygmunt et al. Muscle Nerve. 2024 Nov.

Abstract

Introduction/aims: Studies have demonstrated that certain genotypes in Duchenne muscular dystrophy (DMD) have milder or more severe phenotypes. These studies included individuals treated and not treated with corticosteroids and multiple sites with potentially varying standards of care. We aimed to assess genotype-phenotype correlations for age at loss of ambulation (LoA) in a large cohort of individuals with DMD treated with corticosteroids at one center.

Methods: In this retrospective review of medical records, encounters were included for individuals diagnosed with DMD if prescribed corticosteroids, defined as daily deflazacort or prednisone or high-dose weekend prednisone, for 12 consecutive months. Encounters were excluded if the participants were taking disease-modifying therapy. Data were analyzed using survival analysis for LoA and Fisher's exact tests to assess the percentage of late ambulatory (>14 years old) individuals for selected genotypes.

Results: Overall, 3948 encounters from 555 individuals were included. Survival analysis showed later age at LoA for exon 44 skip amenable (p = .004), deletion exons 3-7 (p < .001) and duplication exon 2 (p = .043) cohorts and earlier age at LoA for the exon 51 skip amenable cohort (p < .001) when compared with the rest of the cohort. Individuals with deletions of exons 3-7 had significantly more late ambulatory individuals than other cohorts (75%), while those with exon 51 skip amenable deletions had significantly fewer (11.9%) compared with other cohorts.

Discussion: This confirms previous observations of genotype-phenotype correlations in DMD and enhances information for trial design and clinical management.

Keywords: Duchenne muscular dystrophy; exon skip; genotype; loss of ambulation; natural history.

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References

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