Relationships between DMD mutations and neurodevelopment in dystrophinopathy

Neurology. 2019 Oct 22;93(17):e1597-e1604. doi: 10.1212/WNL.0000000000008363. Epub 2019 Oct 8.


Objective: We performed a prospective, cross-sectional analysis of neurodevelopmental concerns and psychosocial adjustment in relation to DMD mutations in young steroid-naive boys with dystrophinopathy.

Methods: We evaluated 196 steroid-naive boys with dystrophinopathy who were enrolled in the Finding the Optimal Regimen for Duchenne Muscular Dystrophy trial. The neurodevelopmental concerns and psychosocial adjustment challenges were analyzed in relation to DMD mutation. A parent or legal guardian reported neurodevelopmental concerns in 4 domains (speech, learning and attentional difficulties, and autism spectrum disorder [ASD]) and completed the Personal Adjustment and Role Skills Scale to assess psychosocial adjustment. We also assessed whether boys of DMD carrier mothers were more vulnerable to speech delay and learning difficulties.

Results: We found that 39% of boys were reported to have speech delay with a mean age of speaking at 28 months (range 7-66 months). Learning difficulties were reported in 28% of participants. Inattentive-overactive and oppositional-defiant behavior was reported in 8% and 5% of participants, respectively. Psychosocial adjustment challenges were reported in 4% of participants. An ASD diagnosis was reported in 3 participants. Speech delay and learning difficulties were more common in boys with mutations downstream of DMD exon 45. Neurodevelopmental concerns were not associated with DMD deletion, duplication, or point mutation subtype. Boys of DMD carrier mothers did not have longer speech delay or more learning difficulties.

Conclusion: Our data support evidence for a relationship between neurodevelopmental concerns and DMD mutation. A longitudinal assessment of developmental trajectory is necessary to evaluate how specific DMD mutations affect brain function.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • Double-Blind Method
  • Dystrophin / genetics*
  • Humans
  • Male
  • Muscular Dystrophy, Duchenne / complications*
  • Muscular Dystrophy, Duchenne / drug therapy
  • Muscular Dystrophy, Duchenne / genetics*
  • Muscular Dystrophy, Duchenne / psychology
  • Mutation*
  • Neurodevelopmental Disorders / complications*
  • Neurodevelopmental Disorders / genetics*
  • Neurodevelopmental Disorders / psychology
  • Neuromuscular Agents / therapeutic use
  • Steroids / therapeutic use


  • DMD protein, human
  • Dystrophin
  • Neuromuscular Agents
  • Steroids