Siblings With Duchenne Muscular Dystrophy: Exploring Diagnosis Age and Disease Progression in a Genetic Therapy‐Naïve Cohort
TL;DR
It is suggested that earlier diagnosis, at least in past decades and in the absence of genetic therapy, may not substantially alter disease trajectory, which may not reflect outcomes in a newborn‐screening population, given the ages at diagnosis and the cohort characteristics.
Abstract
Duchenne muscular dystrophy (DMD) is the most common pediatric muscular dystrophy. Typically, there is a ~ 2‐year delay between symptom onset and diagnosis. Limited data on outcomes in early‐diagnosed individuals have limited the understanding of the clinical impact of early diagnosis. We evaluated whether earlier diagnosis is associated with delayed disease progression by analyzing 42 sibling sets (88 individuals) with DMD followed at a single neuromuscular center between 1983 and 2023. Younger siblings were diagnosed at a median age of 2.04 years compared with 4.96 years for older siblings ( p < 0.001) and initiated corticosteroid therapy earlier (4.45 vs. 6.40 years; p < 0.001). Age at diagnosis was not a significant predictor of four key outcomes: age at loss of ambulation, age at first left ventricular ejection fraction < 55%, age at first forced vital capacity < 80%, or motor function scores at age 8 years. Clinical variability was observed even among siblings with the same genetic variant, suggesting additional influences. Younger siblings had significantly shorter follow‐up (median age at last visit: 10.5 vs. 14.4 years; p < 0.001), which may limit the capture of milestones. These findings suggest that earlier diagnosis, at least in past decades and in the absence of genetic therapy, may not substantially alter disease trajectory. This interpretation may not reflect outcomes in a newborn‐screening population, given the ages at diagnosis and the cohort characteristics. Prospective studies are needed as these therapies become more widely used.