Understanding the neurobehavioural impact of Duchenne muscular dystrophy: A multicentre European study

Duchenne muscular dystrophy (DMD) is a severe X-linked disorder characterised by dystrophin deficiency, leading to progressive muscle degeneration and reduced life expectancy. Recent studies report neurodevelopmental and psychiatric comorbidities, though their manifestations remain only partially understood. In this multicentre European study, conducted within the Brain Involvement iN Dystrophinopathies (BIND) consortium, we assessed neurobehavioural outcomes in 238 males aged 5–17 years with genetically confirmed DMD, using standardised parent-report questionnaires. Parent-reported symptoms were reviewed and rated by trained clinicians using criteria from the Diagnostic and Statistical Manual of Mental Disorders (DSM-V1). We compared findings with two UK-based cohorts: (1) children with pathogenic copy number variants (CNVs) from the IMAGINE-ID study [2] (n = 470; matched on sex, chronological age, and parent-estimated mental age), and (2) a male normative population sample [3] (n = 3,851). Clinician-rated Development and Well-Being Assessment (DAWBA) assessments indicated that 21% of participants met criteria for at least one DSM-5 diagnosis, including attention-deficit/hyperactivity disorder (ADHD, 8.4%), anxiety-type disorders (7.9%), and autism spectrum disorder (ASD, 6.7%). Genotype-phenotype analyses within DMD revealed elevated ASD prevalence in individuals with Dp140– variants, while ADHD and anxiety were distributed across genotypic groups. Although the DMD cohort exhibited a less severe neurobehavioral impact than the IMAGINE-ID group, they showed markedly elevated emotional and behavioural difficulties as well as prevalence of DAWBA-based diagnoses compared to normative population data. Our findings underscore the neuropsychiatric burden associated with DMD and support the need for routine screening and stratified care approaches informed by genotype.