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Population-based investigation of DMD genotype and neurodevelopmental concerns in Duchenne Muscular Dystrophy
Journal article   Peer reviewed

Population-based investigation of DMD genotype and neurodevelopmental concerns in Duchenne Muscular Dystrophy

Andrea He, Tahereh Neyaz, Vinay Bhandaru, Madeline Rice, Natalie Street, Katherine Mathews, Yedatore Swamy Venkatesh, Emma Ciafaloni, James Howard, Kristin Conway, …
Neuropediatrics
02/24/2026
DOI: 10.1055/a-2818-7095
PMCID: PMC13081602
PMID: 41734790

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Abstract

BackgroundStudies have shown that individuals with Duchenne Muscular Dystrophy (DMD) with distal DMD variants have higher frequencies of co-occurring neurodevelopmental concerns than those with proximal DMD variants. Whether these associations are generalizable is not known. We investigated the association between DMD genotype and neurodevelopmental concerns in DMD using population-based surveillance data to improve generalizability and better inform clinical care.MethodsMuscularDystrophy Surveillance, Tracking and Research Network (MD STARnet) data was used to investigate neurodevelopmental concerns as a function of DMD genotype in 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 (ORs) and confidence intervals (CIs) 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 variants were calculated.ResultsORs 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 to those with DMD variants in exons 45-62. There were no statistically significant associations between presence of neurodevelopmental concerns and proximal versus distal variant location.ConclusionsPopulation-level data did not show statistically significant associations between neurodevelopmental concerns and DMD variant locations, except in individuals with very distal mutations. The highest neurodevelopmental burden was among individuals with DMD variants in exons 63-79.
Duchenne muscular dystrophy neurodevelopment speech and language delay attention-deficit hyperactivity disorder MD STARnet

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