Spinal Muscular Atrophy: Past, Present, and Future.

Area of Science:

• Genetics
• Neurology
• Pediatrics

Background:

• Spinal muscular atrophy (SMA) is a severe autosomal recessive neuromuscular disorder caused by SMN1 gene defects.
• It leads to progressive muscle weakness and atrophy, being a leading inherited cause of infant mortality.
• Recent advances include FDA-approved treatments and SMA's inclusion in newborn screening panels.

Purpose of the Study:

• To review the clinical history, classification, and current treatments for SMA.
• To discuss the implementation and controversies surrounding SMA newborn screening (NBS).
• To explore experimental treatments and advocate for NBS with essential long-term follow-up.

Main Methods:

• Literature review of SMA diagnosis, classification, and treatment.
• Analysis of the rationale and challenges for including SMA in newborn screening programs.
• Discussion of emerging therapies and ethical considerations for NBS.

Main Results:

• SMA diagnosis has evolved, with new treatments like nusinersen offering hope.
• SMA is now part of recommended newborn screening, but raises concerns due to variable onset.
• Experimental treatments are under investigation, highlighting the need for ongoing research.

Conclusions:

• Newborn screening for SMA is supported, but requires a long-term follow-up registry.
• The registry is essential to balance screening benefits against potential harms, especially for milder SMA forms.
• Ethical implementation of SMA NBS is critical for improving patient outcomes.