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

Extant studies have shown that individuals with Duchenne muscular dystrophy (DMD) with distal <i>DMD</i> variants have higher frequencies of co-occurring neurodevelopmental concerns, compared with those with proximal <i>DMD</i> variants. Whether the reported co-occurrences between <i>DMD</i> genotype and neurodevelopmental concerns in DMD are generalizable is not known. We therefore investigated the association between <i>DMD</i> 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 <i>DMD</i> genotype in 325 individuals with DMD. Proximal <i>DMD</i> variants were defined as those located 5' to <i>DMD</i> exon 45, and distal <i>DMD</i> variants as those located 3' of and including <i>DMD</i> exon 45. Distal <i>DMD</i> variants were further sub-classified into those with very distal variants in <i>DMD</i> 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 <i>versus</i> distal <i>DMD</i> 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 <i>DMD</i> variants in exons 63-79 compared with those with <i>DMD</i> variants in exons 45-62. There were no statistically significant associations between the presence of neurodevelopmental concerns and proximal <i>versus</i> distal <i>DMD</i> variant location.We did not find statistically significant associations between neurodevelopmental concerns and <i>DMD</i> variant locations in population-level data, except for those with very distal <i>DMD</i> mutations. The highest neurodevelopmental burden was among individuals with <i>DMD</i> variants located in exons 63-79.