Genotype–cognitive phenotype associations in Duchenne muscular dystrophy: the role of mutation location and ambulatory status in a pediatric cohort

Duchenne muscular dystrophy (DMD) is characterized by progressive motor decline as well as cognitive impairment and reduced quality of life. This study aimed to investigate the relationship between genotype, cognitive functioning, and quality of life in children with DMD. This cross-sectional study included 37 boys aged 8–12 years with genetically confirmed DMD and deletion mutations. Deletions involving exons before 44 were classified as proximal and those involving exon 44 and beyond as distal. Ambulatory status was recorded as ambulatory or non-ambulatory. Cognitive functioning was assessed using the Wechsler Intelligence Scale for Children–Revised (WISC-R). Psychiatric comorbidities were evaluated with the Kiddie Schedule for Affective Disorders and Schizophrenia–Present and Lifetime Version (K-SADS-PL), and health-related quality of life was assessed using the Pediatric Quality of Life Inventory (PedsQL). Deletions were predominantly located in the distal region of the DMD gene (exon 44 and beyond). The mean total intelligence quotient (IQ) was 79.54 ± 18.27. No significant associations were identified between mutation location and cognitive performance or ambulatory status. Cognitive performance did not differ according to ambulatory status. However, non-ambulatory patients demonstrated significantly lower physical and social health-related quality-of-life scores, and this association with physical functioning remained significant after adjustment for age. Patients receiving special education had significantly lower performance IQ scores and poorer physical health-related quality of life than those not receiving special education, whereas verbal and total IQ scores were comparable. In this cohort, we did not detect an association between mutation location and cognitive functioning. In contrast, health-related quality of life, particularly the physical and social domains, was associated with ambulatory status. These findings should be interpreted cautiously given the limited sample size and support the importance of multidisciplinary care in children with DMD.