Using participatory methods to develop context-specific local government actions to create healthy food and physical activity environments for school-aged children: a case study in Flanders.

Dystrophin-related muscular dystrophies, known as dystrophinopathies, encompass a range of conditions from the severe Duchenne muscular dystrophy (DMD) to the milder Becker muscular dystrophy (BMD). DMD affects approximately 1 in 3500 to 1 in 9300 males, while BMD affects about 1 in 16,700 to 1 in 18,500 males (ORPHA: 98,896 and 98,895, respectively). These X-linked recessive inherited neuromuscular disorders primarily affect males with mutations in the gene, the largest gene in the human genome containing 79 exons. The absence of functional dystrophin, as observed in DMD, and the presence of partially functional dystrophin, as seen in BMD, render muscle fibres prone to damage and degeneration. This leads to progressive muscle weakness and loss of function. The gene comprises several tissue-specific promoters, with the full-length muscle isoform (Dp427m) predominantly expressed in skeletal and cardiac muscle tissues. Additionally, dystrophin is expressed in the brain, where it plays crucial roles in synaptic function, neuronal signalling, and neurodevelopment. High expression levels of dystrophin isoforms Dp427c, Dp140, and Dp71 have been identified in brain regions, including the amygdala, hippocampus, cerebral cortex and cerebellum (Dp427c, Dp140 and Dp71; for reviews see). Although precise mechanisms are not fully understood, several studies suggest that the location of the mutation may play a role in the manifestation and possibly severity of neurodevelopmental problems. These studies have reveal that patients with more distal mutations, which cumulatively affect Dp140 and Dp71, have an increased risk of cognitive deficits and lower IQ. Regardless of mutation site, individuals with DMD have an increased risk of cognitive deficits, and lower IQ, and neuropsychiatric problems compared to the general population. On average, individuals with DMD exhibit IQ scores that are one standard deviation below the population mean (full scale IQ = 84). The cognitive profile in DMD is relatively well-recognized and is characterised by both strengths and weaknesses. Perceptual organisation, abstract reasoning, and visuospatial processing may be relatively well-preserved. In contrast, working memory, verbal/short term memory, attention, executive functioning, and automatization of academics (reading and arithmetic) are frequently affected. Furthermore, several studies indicate that these cognitive deficits can occur regardless of intellectual disability. These cognitive challenges may often interact with behavioural and socio-emotional issues, as many individuals with DMD are also at risk for behavioural, neurodevelopmental and emotional symptoms, as shown in a recent systematic review and meta-analysis. We previously described a theoretical framework to understand the brain related comorbidities in DMD. Specifically, we proposed that there are four domains of interest encompassing ten different and potential areas of problematic functioning (The Big Ten of Duchenne): intelligence, working Memory/Attention and executive function in the cognitive domain (1), reading and arithmetic in the learning domain (2), Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), Obsessive Compulsive Disorder (OCD) in the psychiatric domain (3), and anxiety and depression in the emotional domain (4). In clinical practice, these ten domains may show overlap. Various instruments have been used to assess behavioural and psychological functioning in DMD, but none have specifically been developed for Duchenne-related cognitive functioning. In 2024, two questionnaires have been developed to address this gap: the BELS and the DUMAND. The latter, a 45-item checklist to screen for DMD-associated neurobehavioural difficulties, assessing five categories: cognition and learning, social responsiveness, emotion regulation, externalising behaviour, and eating and sleeping. This was a pilot study incorporating item selection, expert panel assessment for face validity, comprehensiveness, and a pilot validation study in a DMD sample of 20 boys with DMD. The second study is on the newly developed 48 item BELS questionnaire: a screening for Behavioural, Emotional, Learning and Social difficulties (12 items per domain). This tool has been administered in an initial pilot study in 34 caregivers of Duchenne patients and 11 Becker patients with an age range between 4–19 year, visiting a neuromuscular clinic in the USA.