We investigated the association of DMD genotype and neurodevelopmental concerns using population-based surveillance data to improve the generalizability of knowledge and better inform clinical care and public health policy.

Extant studies have shown that individuals with dystrophinopathies with distal DMD variants have higher frequencies of co-occurring neurodevelopmental concerns, compared to those with proximal DMD variants. Whether the reported co-occurrences between DMD genotype and neurodevelopmental concerns are generalizable is not known.

We used the population-based Muscular Dystrophy Surveillance, Tracking and Research Network (MD STARnet) data (n = 350) and analyzed neurodevelopmental concerns as a function of DMD genotype, and calculated the frequencies of speech/language delay (SLD), autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), cognitive dysfunction, intellectual disability (ID), and global developmental delay (GDD). We defined proximal DMD variants 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 sub-classified into those with very distal variants in DMD exons 63-79.

SLD were the most common neurodevelopmental concern in our dystrophinopathies cohort (50%). The frequencies of ASD, ADHD, OCD, GDD were comparable between those individuals with proximal versus distal DMD variants. Although multiple neurodevelopmental concerns were more frequent in individuals with distal DMD variants (47%) compared to those individuals with proximal DMD variants (41%), the difference did not reach statistical significance. Individuals with variants in DMD exons 63 to 79 had highest frequencies of ID (43%) and GDD (86%), as well as multiple neurodevelopmental concerns (86%).

There was no statistically significant association between the burden of neurodevelopmental concerns and DMD genotype in the MDSTARnet data but dystrophinopathy individuals with variants located in DMD exons 63 to 79 had statistically significant higher frequencies of ID, GDD, and multiple neurodevelopmental concerns.