Systematic Literature Review of the Natural History of Spinal Muscular Atrophy: Motor Function, Scoliosis, and Contractures.

BACKGROUND AND OBJECTIVES Spinal muscular atrophy (SMA) is a progressive neuromuscular disorder associated with continuous motor function loss and complications such as scoliosis and contractures. Understanding the natural history of SMA is key to demonstrating the long-term outcomes of SMA treatments. This study reviews the natural history of motor function, scoliosis, and contractures in patients with SMA. METHODS Electronic databases were searched from inception to June 27, 2022 (Embase, MEDLINE, and Evidence-Based Medicine Reviews). Observational studies, case-control studies, cross-sectional studies, and case series reporting on motor function (i.e., sitting, standing, and walking ability), scoliosis, and contracture outcomes in patients with Types 1-3 SMA were included. Data on study design, baseline characteristics, and treatment outcomes were extracted. Datasets were generated from studies that reported Kaplan-Meier (KM) curves and pooled to generate overall KM curves. RESULTS Ninety-three publications were included, of which 68 reported on motor function. Of these, 10 reported KM curves (three on the probability of sitting in patients with Types 2 and 3 SMA, and eight on the probability of walking/ambulation in patients with Type 3 SMA). The median time to loss of sitting (95% confidence interval [CI]) was 14.5 years (14.1-31.5) for the Type 2 SMA sitter population (their maximum ability was independent sitting). The median time to loss of ambulation (95% CI) was 13.4 years (12.5-14.5) for Type 3a SMA (disease onset at age