Population-Based Investigation of DMD Genotype and Neurodevelopmental Concerns in Duchenne Muscular Dystrophy

Abstract Extant studies have shown that individuals with Duchenne muscular dystrophy (DMD) with distal DMD variants have higher frequencies of co-occurring neurodevelopmental concerns, compared with those with proximal DMD variants. Whether the reported co-occurrences between DMD genotype and neurodevelopmental concerns in DMD are generalizable is not known. We therefore investigated the association between DMD genotype and neurodevelopmental concerns in DMD using population-based surveillance data to improve the generalizability of knowledge and better inform clinical care. The population-based Muscular Dystrophy Surveillance, Tracking and Research Network (MD STARnet) data were used to investigate the neurodevelopmental concerns as a function of DMD genotype in 325 individuals with DMD. Proximal DMD variants were defined as those located 5′ to DMD exon 45, and distal DMD variants as those located 3′ of and including DMD exon 45. Distal DMD variants were further sub-classified into those with very distal variants in DMD exons 63–79. Odds ratios and confidence intervals of speech/language delay, autism spectrum disorder, attention-deficit hyperactivity disorder, obsessive-compulsive disorder, cognitive dysfunction, intellectual disability, and global developmental delay between proximal versus distal DMD variants were calculated. The odds ratios were highest for global developmental delay (17.09), multiple neurodevelopmental concerns (8.0), and intellectual disability (6.95) in those with DMD variants in exons 63–79 compared with those with DMD variants in exons 45–62. There were no statistically significant associations between the presence of neurodevelopmental concerns and proximal versus distal DMD variant location. We did not find statistically significant associations between neurodevelopmental concerns and DMD variant locations in population-level data, except for those with very distal DMD mutations. The highest neurodevelopmental burden was among individuals with DMD variants located in exons 63–79.