AUTHOR=Dosi Claudia , Masson Riccardo 

TITLE=The impact of three SMN2 gene copies on clinical characteristics and effect of disease-modifying treatment in patients with spinal muscular atrophy: a systematic literature review

JOURNAL=Frontiers in Neurology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1308296

DOI=10.3389/fneur.2024.1308296

ISSN=1664-2295

ABSTRACT=<sec id="sec1"><title>Objective</title><p>To review the clinical characteristics and effect of treatment in patients with spinal muscular atrophy (SMA) and three copies of the <italic>SMN2</italic> gene.</p></sec><sec id="sec2"><title>Methods</title><p>We conducted a literature search in October 2022 to identify English-language clinical research on SMA that included <italic>SMN2</italic> copy number according to PRISMA guidelines.</p></sec><sec id="sec3"><title>Results</title><p>Our search identified 44 studies examining the impact of three <italic>SMN2</italic> copies on clinical characteristics (21 on phenotype, 13 on natural history, and 15 on functional status and other signs/symptoms). In children with type I SMA or presymptomatic infants with an <italic>SMN1</italic> deletion, three <italic>SMN2</italic> copies was associated with later symptom onset, slower decline in motor function and longer survival compared with two <italic>SMN2</italic> copies. In patients with SMA type II or III, three <italic>SMN2</italic> copies is associated with earlier symptom onset, loss of ambulation, and ventilator dependence compared with four <italic>SMN2</italic> copies. Eleven studies examined treatment effects with nusinersen (nine studies), onasemnogene abeparvovec (one study), and a range of treatments (one study) in patients with three <italic>SMN2</italic> copies. In presymptomatic infants, early treatment delayed the onset of symptoms and maintained motor function in those with three <italic>SMN2</italic> copies. The impact of copy number on treatment response in symptomatic patients is still unclear.</p></sec><sec id="sec4"><title>Conclusion</title><p><italic>SMN2</italic> copy number is strongly correlated with SMA phenotype in patients with <italic>SMN1</italic> deletion, while no correlation was found in patients with an <italic>SMN1</italic> mutation. Patients with three <italic>SMN2</italic> copies show a highly variable clinical phenotype. Early initiation of treatment is highly effective in presymptomatic patients with three <italic>SMN2</italic> copies.</p></sec>