Background: Spinal muscular atrophy (SMA) is caused by abnormalities of the survival motor neuron (SMN) 1 gene, leading to a deficiency in SMN protein and a loss of spinal cord alpha motor neurons. Newer disease-modifying agents (DMA) targeting the involved genes – including Nusinersen and gene replacement therapies – have improved gross motor and respiratory function, but their impact on scoliosis development has not been established.
Objectives: To determine the prevalence and risk factors for scoliosis development in SMA, specifically genetic severity (by SMN2 copy number) and DMA use. We hypothesized that genetic severity by decreased SMN 2 copy number would increase the scoliosis risk, while DMA use would be protective.
Methods: Retrospective cohort. Children with SMA and minimum 2-year follow-up, were included. Primary outcome was the prevalence of clinically-relevant scoliosis [major curve (MC) ≥40%]. Secondary outcomes included: SMA Type (I/II/III), SMN2 copy number (<3 or ≥3), Hammersmith Functional Motor Scale (HFMS), ambulatory status [Functional Mobility Scale at 50m (FMS50)], DMA use (>1y duration, Nusinersen/Risdiplam/Onosemnogene/Abeparvovec) and hip displacement [migration percentage (MP≥40%)], as risk factors. Univariate/multivariate logistic regression analyses for identification of risk factors were performed.
Results: 82 patients (52% female) with SMA Type I(44%), II(39%), and III(17%) met the inclusion criteria, with a total follow-up duration of 7.3(SD:4.5) years. The prevalence of scoliosis was 52.4%, with age of onset 7.2(SD:3.0) years. By SMA type, the prevalence/age of onset was 68.7%/5.1 years, 50.0%/8.5 years, and 21.4%/11.6 years, for I, II, and III, respectively. The age at first scoliosis x-ray was 5.5(SD:3.2) years, with major curve amplitude 34(SD:22)˚. At last follow-up, the major curve amplitude was 48(SD:29)˚. Significant risk factors for scoliosis by univariate analysis were: SMA Type (I/II, p=0.006/0.08), SMN2 copy (<3, p=0.03), non-ambulatory status (FMS50=1, p=0.04), and hip displacement (p<0.001). Multivariate analysis revealed that only hip displacement was an independent risk factor (p=0.002) (Table).
Conclusions: The development of scoliosis in SMA is high, with risk factors associated with proxy measures of disease severity, including SMN2 copy number, SMA type, ambulatory status and, most notably, the presence of hip displacement. DMA use was not found to be protective for scoliosis development.