The Spinal Muscular Atrophy Functional Classification System

AIM: To develop a functional mobility classification for spinal muscular atrophy (SMA), reflecting changing phenotypes in the era of disease-modifying agents, with associations to hip displacement, scoliosis, and pulmonary function determined. METHOD: Patients with SMA and Hammersmith Functional Motor Scale Expanded (HFMSE) assessments were included. The Spinal Muscular Atrophy Functional Classification System (SMAFCS), comprising levels I to IV, was constructed, referencing Functional Mobility Scale groupings. Receiver-operating characteristic analysis determined HFMSE thresholds by SMAFCS. Associations of hip displacement, scoliosis, and pulmonary function were determined. RESULTS: Sixty patients (62% female) were included, with 312 HFMSE assessments (mean 5.3 [SD 2.7] per patient) over 7 years 6 months (SD 3 years 11 months). HFMSE thresholds by SMAFCS level were I, ≥27; II, ≥22, <27; III, ≥10, <22; IV, <10 (area under the curve 0.62-0.89; p < 0.001). HFMSE versus SMAFCS age trajectories were modeled, significant for levels I (p = 0.002), III (p < 0.001), and IV (p = 0.002) but not level II (p = 0.48). The prevalences of hip displacement and scoliosis by SMAFCS level were respectively I, 61%; II, 50%; III, 92%; IV, 96% (p = 0.008) and I, 42%; II, 50%; III, 85%; IV, 96% (p < 0.001). Pulmonary function (forced vital capacity percent of predicted) worsened by SMAFCS level: I, 96 (SD 15); II, 83 (SD 12); III, 75 (SD 16); IV, 48 (SD 27) (p < 0.001). INTERPRETATION: These preliminary data suggest the SMAFCS could be a valuable tool to stratify gross motor function and predict risk of clinical outcomes in SMA. Further work is required to study reliability and responsiveness to change.