Genotype-informed orthopedic management, utilizing quantitative thresholds like Cobb angle ≥20-30° and FVC ≥30-35% for scoliosis in Duchenne muscular dystrophy, is proposed to improve outcomes.
This review provides a practical roadmap for translating genomic insights into durable functional outcomes through precision orthopedics in muscular dystrophies.
Muscle degeneration is the hallmark of muscular dystrophies—genetically heterogeneous disorders traditionally approached through the lens of molecular pathogenesis or symptomatic management in isolation. Here, we present a deliberately interdisciplinary synthesis that bridges molecular genetics, clinical phenotyping, and evidence-based orthopedic decision-making to address a significant critical gap: the lack of genotype-informed, function-oriented frameworks for musculoskeletal complications. We re-evaluate disease entities—not only by their molecular etiology (e.g., DMD, LMNA, DUX4 dysregulation), but through the prism of orthopedic manifestations as diagnostic gateways and therapeutic milestones. For instance, early rigid spine in LMNA-related dystrophy is not merely a sign of contracture, but a red flag demanding cardiac risk stratification before surgical planning, in alignment with current consensus. Similarly, scoliosis management in Duchenne muscular dystrophy is discussed through quantitative decision thresholds (Cobb angle ≥ 20–30°, FVC ≥ 30–35%) derived from long-term outcome studies, rather than general clinical recommendations. Critically, we confront challenges posed by disease-modifying therapies: patients now survive into their 30s and 40s, yet develop novel, therapy-exacerbated orthopedic phenotypes (e.g., steroid-induced osteoporosis, atypical spinal rigidity). Therefore, we argue that precision orthopedics—tailored surveillance, genotype-stratified intervention timing (e.g., D4Z4 repeat-guided monitoring in FSHD, and realistic functional goal-setting (e.g., scapular arthrodesis for overhead function)—should become the gold standard of care. For example, desminopathies may show marked phenotypic variability even within the same mutation. Our review thus serves not only as a molecular overview, but as a practical roadmap for neurologists, geneticists, orthopedic surgeons, and rehabilitation specialists seeking to translate genomic insights into durable functional outcomes.
Lejman et al. (Mon,) conducted a review in Muscular Dystrophies. Genotype-informed orthopedic management, utilizing quantitative thresholds like Cobb angle ≥20-30° and FVC ≥30-35% for scoliosis in Duchenne muscular dystrophy, is proposed to improve outcomes.