Neuropsychological functioning and quality of life in congenital myopathies: a systematic review of children and caregiver outcomes
Background Congenital myopathies (CMs) are a heterogeneous group of rare or ultra-rare inherited muscular disorders in which cognitive, neuropsychological and psychosocial outcomes remain poorly characterized. Objective To synthesize current evidence on cognitive development, neuropsychological and quality-of-life (QoL) outcomes in pediatric CMs, including caregiver burden. Methods A systematic review was conducted according to PRISMA guidelines and registered on PROSPERO (CRD420261373780). PubMed, Scopus, Web of Science and ClinicalTrials.gov were searched up to June 2026. Observational studies reporting neuropsychological or psychosocial outcomes in children with CMs were included. Results 18 studies (104 patients; 56 caregivers) were included, predominantly case reports/series (72.2%). Cognitive outcomes were heterogeneous: most patients showed preserved intellectual functioning; however, beyond the expected motor impairment, some exhibited additional language or domain-specific deficits. More severe profiles were observed in ACTA1-related disease and selected rare genotypes, often associated with brain abnormalities. In contrast, cognition was largely preserved in X-linked myotubular myopathy, although adaptive functioning and QoL were frequently reduced. School outcomes were rarely reported. Caregiver data indicated a substantial and multidimensional burden. Conclusion Neuropsychological and psychosocial outcomes in pediatric CMs are clinically relevant but understudied and heterogeneous across genotypes. Standardized, motor-adapted assessment should be integrated into multidisciplinary care. QoL evidence remains limited to XLMTM and SELENON-related myopathy. Prospective, genotype-stratified studies including longitudinal, academic, adaptive and caregiver outcomes are needed, particularly alongside emerging disease-modifying therapies. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420261373780, identifier CRD420261373780.