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

Authors

• Andrea He, Department of Neurology, Virginia Commonwealth University Medical Center, Richmond, Virginia, United States.
• Tahereh Neyaz, College of Public Health, University of Iowa, Iowa City, Iowa, United States.
• Vinay Bhandaru, Milken School of Public Health, George Washington University Biostatistics Center, Washington, District of Columbia, United States.
• Madeline Rice, Milken School of Public Health, George Washington University Biostatistics Center, Washington, District of Columbia, United States.
• Natalie Street, Centers for Disease Control and Prevention, National Center on Birth Defects and Developmental Disabilities, Atlanta, Georgia, United States.
• Katherine Mathews, Stead Family Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States.
• Yedatore Swamy Venkatesh, Department of Neurology, University of South Carolina School of Medicine, Columbia, South Carolina, United States.
• Emma Ciafaloni, Department of Neurology, University of Rochester, Rochester, New York, United States.
• James Howard, Department of Neurology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States.
• Kristin M. Conway, College of Public Health, University of Iowa, Iowa City, Iowa, United States.
• Mathula Thangarajh, Department of Neurology, Virginia Commonwealth University Medical Center, Richmond, Virginia, United States.

Document Type

Journal Article

Publication Date

3-10-2026

Journal

Neuropediatrics

DOI

10.1055/a-2818-7095

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.

APA Citation

He, Andrea; Neyaz, Tahereh; Bhandaru, Vinay; Rice, Madeline; Street, Natalie; Mathews, Katherine; Venkatesh, Yedatore Swamy; Ciafaloni, Emma; Howard, James; Conway, Kristin M.; and Thangarajh, Mathula, "Population-Based Investigation of DMD Genotype and Neurodevelopmental Concerns in Duchenne Muscular Dystrophy" (2026). GW Authored Works. Paper 8916.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/8916

Department

Epidemiology