In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled: Global prevalence of Duchenne and Becker muscular dystrophy: a systematic review and meta-analysis.
Today’s pick is from Journal of Orthopaedic Surgery and Research by Salari et al on the global prevalence of Duchenne & Becker through a systematic meta analysis. Authors are from Iran and included English and Persian papers in analysis. Doi 10.1186/s13018-022-02996-8.
Duchenne & Becker muscular dystrophy (DMD/BMD) are caused by mutations in the dystrophin gene. DMD is the severe form caused by mutations preventing production of functional dystrophin, BMD is a milder form caused by mutations allowing production of partially functional dystrophin.
The dystrophin gene is located on the X-chromosome and the inheritance of DMD and BMD is X-linked recessive, so mainly males are affected, while females are carriers. Some carriers are symptomatic – speculated to be because of skewed X-inactivation.
Not in the paper but important to bear in mind: some females have DMD or BMD, e.g. BMD females can have dystrophin mutations on both X chromosomes, and DMD females can have only a single, dystrophin mutated (active) X chromosome (Turner, translocation).
Because female DMD is so rare, it is often diagnosed very late – see e.g. this case study https://pubmed.ncbi.nlm.nih.gov/34595143/. Authors here studied the prevalence of DMD and BMD (reminder: incidence is how many are born, prevalence is how many patients there are).
Authors performed a meta-analysis using The Cochrane Library method. 1883 articles were retrieved from various databases in English & Persian. After filtering out duplicates/irrelevant papers, 25 articles were left covering >90 million people (abstract says 900 million due to typo).
Publications were published between 1982 and 2021. Since not all cohort sizes were equal, authors used sensitivity analysis to rule out e.g. a small cohort study over contributing to the prevalence. Incidence worldwide is 3.6 per 100,000 (1 per 28,000) for all muscular dystrophies.
Prevalence for DMD is 4.8 per 100,000 (1 per 21,000). For BMD it is 1.6 per 100,000 (1 per 62,500). Authors discuss prevalence is highest in the Americas & lowest in Africa – I think there may be underdiagnosis in Africa. Authors correctly point out increased awareness is needed.
Awareness results in earlier diagnosis, access to care (see care guidelines on TREAT-NMD website), genetic counselling (mother may be a carrier, her sisters, cousins etc may also be a carrier).
Finally, mutation specific therapies are approved at different areas of the world (exon skipping & stop codon readthrough). For this is it important to do genetic diagnosis – more information here: https://pubmed.ncbi.nlm.nih.gov/26754139/ (an educational paper I wrote in 2016 – still relevant!)
I like the systematic approach the authors used and I also like that they included papers beyond the English papers – likely there are more papers out there in native languages as the authors point out. With increased awareness and improved diagnosis globally prevalence may go up.
Pictures by Annemieke, used with permission.