A self-reported Brazilian registry of spinal muscular atrophy: data from natural history, genetic characteristics, and multidisciplinary care

Abstract

Abstract Background. Spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by mutations in the SMN1 gene. This study is intended to describe the key demographic, clinical and genetic characteristics, and natural history data of patients with SMA registered through a self-reported survey by patients or their parents. Results. By January 2022, 706 patients with 5q SMA had completed the questionnaire and had confirmatory molecular testing. Most patients reported having type 1 SMA (42%); 33% had type 2 SMA, and 23% had type 3 SMA. Six hundred sixty-seven patients (94.4%) had a homozygous SMN1-exon 7 deletion. One hundred thirty-one (18.6%) patients had a previous family history, and the familial recurrence rate was higher in patients with type 3 SMA, at 25.6%. The consanguinity rate was 5.2% in the studied population. 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 SMA without invasive ventilation was 27 months. Before 2018, the median age at the endpoint was 16 months, and after 2018, most patients (71%) were not submitted to invasive ventilation. About 50% of patients with type 3 SMA lost their walking ability by 37 years of age. Three hundred eighty-four (54.4%) patients claimed to have had access to some disease-modifying therapy, and 62.3% of type 1 patients were in treatment, while only 47.2% of type 2 SMA patients and 31.9% of type 3 SMA patients were in treatment. Conclusions. This is the first Brazilian registry of SMA and evidenced the accuracy and reliability of patient-reported data compared to previous studies. There is still a substantial diagnostic delay, especially in those patients with types 2 and 3 SMA. However, the study demonstrated prolonged survival, especially in type 1 patients.