Diagnosis, Treatment, and the Burden of Disease for Duchenne Muscular Dystrophy (DMD) in Females: A Targeted Literature Review (TLR)

OBJECTIVES: Research in DMD, a rare, X-linked disease, generally focuses on males. Though female carriers may experience symptoms, beyond recommendations for access to testing, guidelines for the management of DMD in females are sparse. This TLR sought to characterize the burden and management of female patients with DMD dystrophinopathy and carriers.

METHODS: Searches were conducted in June 2023 in eight databases using search terms for DMD and females. All retrieved records including case series and reports were screened. Studies reporting on disease burden, diagnostic pathways, treatment pathways, and outcomes were eligible. Newer papers (2015-2023) reporting on higher numbers of patients, with either detailed data or >1 outcome reported, were prioritised for extraction, and key guidelines were also synthesised.

RESULTS: From 2,058 records, 82 relevant papers were identified; 13 studies were extracted. Cardiac outcomes were common in carriers; the cardiac abnormality rate (variously defined) was 50% to 100% among 90 carriers across 4 studies. In a study comparing female carriers to males with a likely DMD mutation, mean age at dilated cardiomyopathy diagnosis was significantly later for females (p<0.001). Among carriers, ~8% had muscle symptoms (2 studies). Two studies, both using cognitive assessment tools in carriers and non-carriers, described reduced cognitive performance on some sub-domains among carriers relative to non-carriers. In 4 studies reporting diagnostic pathways, methods of diagnosis were not systematic.

CONCLUSIONS: This review indicates a large proportion of female patients with DMD dystrophinopathy and carriers are affected, especially by cardiac, but also by muscular and/or cognitive difficulties. Data on diagnostic pathways used was limited; pathways followed do not always reflect best practice. A limitation of this review is that case reports, which were not extracted, may contain information related to treatment pathways/outcomes. Our findings suggest that this population is under-investigated, and given their unmet medical need, additional research is necessary.