The natural history of Becker muscular dystrophy: A systematic literature review.

BACKGROUND

Becker muscular dystrophy (BMD) is caused primarily by in-frame mutations in the DMD gene. Phenotype varies from asymptomatic to severe; manifestations may include muscle weakness, scoliosis, cardiac involvement, loss of ambulation, respiratory impairment, cognitive dysfunction, and premature death. This study aimed to characterize the frequency and age at occurrence of these milestones.

METHODS

A systematic literature review (SLR) was refreshed in 2022 using MEDLINE and EMBASE to identify articles describing the natural history of BMD. The proportion of patients experiencing clinical milestones was reported by 'life-stage' age groups (0-17; 18-40; 41+ years) using patient-level data from the general BMD population; age at each milestone's occurrence as mean (standard deviation [SD]).

RESULTS

From 4948 abstracts screened, 121 publications were included. Among 36 general BMD population studies, by age 41+ years (lifetime-risk proxy), 93.6% experienced muscle weakness; 69.4% cardiac involvement; 55.6% scoliosis; 47.4% loss of ambulation; and 33.3% ventilation. Decreased cognitive function or cognitive dysfunction were reported in 41% across all ages. Among those experiencing milestones (79 studies), mean (SD) age at symptom onset was 12.5 (9.7); muscle weakness, 19.9 (11.7); scoliosis, 24.9 (3.1); cardiac involvement, 31.9 (13.4); loss of ambulation, 33.3 (13.5); ventilation, 35.7 (12.2); and death at 55.6 (19.4) years. Data availability ranged from three to 1079 patients/outcome.

CONCLUSIONS

This SLR highlights the variability in disease presentation in BMD. Stratifying BMD populations into phenotype groups based on the full spectrum of clinical manifestations may better capture disease progression and enhance comparability across studies.Included clinical trials:ClinicalTrials.gov NCT01070511 (https://clinicaltrials.gov/study/NCT01070511), ClinicalTrials.gov NCT02147639 (https://clinicaltrials.gov/study/NCT02147639?term=Becker%20Muscular%20Dystrophy&intr=Sodium%20Nitrate&rank=3), ClinicalTrials.gov NCT01350154 and EudraCT number: 2010-024659-10 (https://clinicaltrials.gov/study/NCT01350154?term=NCT01350154&rank=1; https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-024659-10/results).