Clinical-epidemiological profile and motor function data of patients with spinal muscular atrophy and four or more copies of SMN2

Abstract

Background: The clinical phenotype of individuals with Spinal Muscular Atrophy linked to chromosome 5q (SMA-5q) with four or more copies of the SMN2 gene are still poorly described, and the initiation of treatment in the pre-symptomatic phase remains controversial. Characterizing this group is essential to guide therapeutic decisions and public policies. Objective: We aim to describe the clinical, functional, and therapeutic profiles of patients with SMA-5q and four or more SMN2 copies who were followed up at a specialized center. Methods: Clinical, functional and treatment variables were analyzed in this cross-sectional and retrospective study of 37 patients with SMA-5q with 4 or more copies of SMN2. Results: Thirty seven patients (11.8%) among a cohort of 313 SMA-5q patients had 4 or more copies of SMN2. The mean age was 31.8 years (4–55), and 70% were male. Seven patients were SMA-5q type 2, twenty four were type 3, five were type 4, and one was in pre-symptomatic stage. Most had four copies of SMN2 (n=35), and two cases had 5 or 6 copies. The mean age at symptoms onset was 6.7 years (0–26 years), and the mean age at diagnosis was 16.6 years (1–53 years), with an estimated interval between first clinical manifestation and diagnosis of 10 years. Among the 23 treated patients, twenty received nusinersen (mean: 3.5 years of treatment) and three received risdiplam, with a mean age at treatment initiation of 299 months (ranging from 36 to 624 months). The mean time between the onset of symptoms and access to treatment was 242 months. All treated patients received only one disease-modifying therapy, and twelve of them reported motor gains or symptom stabilization. Conclusion: Although patients with SMA-5q and at least four copies of SMN2 usually present with milder phenotype, severe phenotypes, such as SMA-5q type 2 can occur, with higher morbidity and socioeconomic impact. Therefore, there is a need to reevaluate the inclusion of these patients in therapeutic protocols and public policies.