Newborn Screening for Duchenne Muscular Dystrophy: Contemporary Considerations for Implementation of an Early Diagnostic Paradigm

PURPOSE OF REVIEW: variants in NBS algorithms. In an evolving model of care, the challenges and potential factors that may strengthen the practice of family-centered care are considered. RECENT FINDINGS: Contemporary DMD NBS programs have adopted measurement of the muscle isoform of creatine kinase (CK-MM), after US Food and Drug Administration approval of high-throughput assays in 2020. Since then, 7 pilot studies from China, Taiwan, and the United States have reported outcomes using varied screening algorithms. Those incorporating repeat dried blood spot (DBS) testing after an initially elevated CK-MM level increased the positive predictive value compared with single-sample screening. Incorporating molecular genomic analysis of DMD in infants with persistently elevated CK-MM levels further increased the positive predictive value to 100%; however, this multistep approach also highlighted the practical challenges of DBS recollection, with a 17.1% (108/632) attrition rate before confirmatory testing. The choice of screening algorithm also determined the scope of conditions identified. The optimal timing for initiation of disease-modifying therapies is uncertain, and this represents a key priority for future research. The recommended model of care for DMD in early life incorporates genetics; psychosocial support; proactive monitoring and individualized support for cognitive, behavioral, and emotional difficulties; access to educational resources and support networks; and clinical trial readiness. SUMMARY: Health system preparedness, collaboration across countries, and coordination mechanisms within a multidisciplinary team are important for building effective health care in the context of early diagnosis of DMD through NBS. There is an ongoing need to evaluate screening algorithms using large systematic data sets, assess their cost-effectiveness, explore the potential for earlier initiation of disease-modifying treatments with validated outcome measurement tools, and establish a comprehensive evidence-based model of care to support global implementation of DMD within NBS programs.