Abstract
BACKGROUND: Spinal muscular atrophy linked to chromosome 5q (SMA-5q) is a neurodegenerative disorder caused by mutations in the SMN1 gene. OBJECTIVE: To describe the key demographic, clinical and genetic characteristics, as well as natural history data of patients with SMA-5q. METHODS: Up to January 2022, 706 patients with confirmed genetic diagnosis of SMA-5q, or their parents, completed a self-reported questionnaire on natural history, genetic characteristics, drug treatments, and multidisciplinary care. RESULTS: Most patients had type 1 SMA-5q (42%); with 33% having type 2, and 23% type 3. There were 667 patients (94.4%) with a homozygous SMN1-exon 7 deletion. Of the total, 131 (18.6%) patients had a previous family history of the disease, and the familial recurrence rate was higher in type 3 (25.6%). Type 1 patients had a mean age of 3 months at the onset of symptoms and a delay of more than 3 months until genetic diagnosis. The median survival of patients with type 1 without invasive ventilation was 27 months. Before 2018, the median age of use of invasive ventilation was 16 months and, after, most patients (71%) were not submitted to invasive ventilation. About 50% of patients with type 3 lost their walking ability by 37 years of age. Further, 384 (54.4%) patients had access to disease-modifying therapy, and 62.3% of type 1 patients were in treatment, compared with only 47.2% of type 2 and 31.9% of type 3 patients. CONCLUSION: There is still a substantial diagnostic delay, especially in those patients with types 2 and 3 SMA-5q. However, the present study demonstrated prolonged survival, especially in type 1 patients.