Presymptomatic detection of spinal muscular atrophy: Ongoing revolution for a devastating disorder

Spinal muscular atrophy (SMA) is an autosomal recessive genetic disorder characterized by progressive degeneration of motoneurons, which used to lead in many cases to severe motor impairment and early death without treatment. In recent years, three disease-modifying treatments have dramatically changed the patient outcome, especially when initiated in the presymptomatic phase. This review examines the scientific rationale, practical implications as well as ethical, economic and political considerations of presymptomatic detection of SMA in the era of transformative therapies. The need for early detection and early treatment of SMA has prompted the implementation of newborn screening programs. All clinical trials and real-life surveys have consistently demonstrated the clear benefits of this strategy for patients. This DNA-based newborn screening method followed by gene-related treatments has inaugurated a new paradigm and has challenged the organization of healthcare systems. This strategy has raised ethical questions about management of uncertainties, which should be overcome by long-term follow-up and transparent information given to the parents. Cost-effectiveness studies have shown that the SMA newborn screening strategy is always dominant over post-symptomatic treatment. Despite the compelling evidence accumulating in favor of newborn screening for SMA, the implementation of systematic routine programs has faced political hurdles in many cases and is not yet effective even in all EU countries. The experience of SMA newborn screening will probably be helpful for upcoming genomic newborn screenings.