Understanding the neurobehavioural impact of Duchenne muscular dystrophy: A multicentre European study
Duchenne muscular dystrophy (DMD) is primarily known for its effects on muscles, but it can also affect how children and young people think, learn, communicate and manage emotions and behaviour. However, estimates of how common these difficulties are have varied considerably between previous studies.
In this multicentre European study, researchers from the BIND Consortium investigated neurodevelopmental and emotional difficulties in 238 boys with DMD aged 5–17 years. Parents completed standardised questionnaires and interviews, which were reviewed by clinicians to identify symptoms associated with conditions such as attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and anxiety disorders. The researchers also compared the findings with data from children with genetic forms of intellectual disability and with a UK population sample.
Overall, 21% of the children with DMD met criteria for at least one neurodevelopmental or psychiatric diagnosis. ADHD, anxiety-type disorders and ASD were the most frequently identified conditions. Compared with the UK population sample, children with DMD had higher rates of ADHD, ASD and anxiety-type disorders, as well as greater emotional and peer-related difficulties.
The study also found evidence that the genetic changes underlying DMD may influence some neurobehavioural outcomes. In particular, ASD was more common among boys whose mutations affected the brain-expressed dystrophin isoform Dp140. However, ADHD and anxiety-type disorders were found across different genetic groups, suggesting that their causes are likely to be more complex.
The findings highlight that brain-related and neurobehavioural difficulties are an important part of DMD and support the value of routinely identifying these difficulties as part of comprehensive care.
Scientific Summary
Kolesnik et al conducted a multicentre European study within the BIND Consortium to characterise neurodevelopmental, emotional and behavioural comorbidities in boys with genetically confirmed Duchenne muscular dystrophy. The study included 238 males aged 5–17 years recruited through neuromuscular clinics, registries and advocacy organisations across Europe. Participants were assessed using the Development and Well-Being Assessment (DAWBA) and Strengths and Difficulties Questionnaire (SDQ).
Overall, 21% of participants met criteria for at least one DSM-5-compatible diagnosis. The most frequently identified diagnoses were ADHD (8.4%), anxiety-type disorders (7.9%) and ASD (6.7%). Compared with UK normative data, the DMD cohort had significantly higher rates of ADHD, ASD and anxiety-type disorders. SDQ scores similarly indicated greater emotional symptoms, peer relationship difficulties and overall impact compared with population norms.
The study also investigated genotype–phenotype relationships according to the predicted impact of DMD variants on dystrophin isoforms. ASD was significantly more prevalent in participants with Dp140-negative variants: 14.3% in the Dp140− group compared with 4.8% in the Dp140+ group and 2.1% in the Dp140-unknown group. In contrast, overall rates of neurobehavioural diagnoses did not differ significantly between genotype groups, and ADHD and anxiety-type disorders were distributed across groups. This suggests that some neurodevelopmental outcomes may be associated with specific dystrophin isoforms, while others are likely to have multifactorial causes.
The study also identified age-related differences in individual SDQ domains: emotional symptoms increased with age, while conduct problems and hyperactivity decreased. Importantly, there was substantial variation between participating sites in both SDQ scores and DAWBA-based diagnoses, highlighting the potential influence of cultural, healthcare-system and reporting differences in multinational neurobehavioural research.
A key strength of the study is its relatively large, multicentre cohort and use of harmonised assessment procedures, alongside comparison with both population norms and a genetically defined comparison group. Limitations include reliance primarily on parent-report measures, limited measures of physical disease progression, and cross-site differences in reported outcomes. The authors therefore emphasise the need for further studies integrating genotype, neuroimaging and behavioural data, as well as direct reports from children and young people and other informants such as teachers.
Take home messages
- Neurobehavioural difficulties are an important part of DMD. In this cohort, 21% of boys met criteria for at least one DSM-5-compatible neurodevelopmental or psychiatric diagnosis.
- ADHD, anxiety and ASD were the most frequently identified conditions, affecting 8.4%, 7.9% and 6.7% of participants, respectively.
- DMD was associated with greater neurobehavioural difficulties than population norms, including higher rates of ADHD, ASD and anxiety, as well as increased emotional and peer-related difficulties.
- Genotype may influence specific neurobehavioural outcomes. ASD was significantly more common in boys with variants affecting Dp140, supporting a possible relationship between brain dystrophin isoforms and neurodevelopmental phenotype.
- Not all neurobehavioural difficulties showed the same genotype relationship. ADHD and anxiety occurred across genotype groups, suggesting that these outcomes are likely influenced by multiple biological and environmental factors.
- Standardised neurobehavioural assessment is feasible across international DMD centres, supporting the development of more systematic approaches to identifying and addressing brain-related comorbidities as part of DMD care
