Genotype – phenotype correlation of Spinal Muscular Atrophy in the era of disease modifying therapies: A tertiary Indian experience

AIM: To correlate SMN2 CN with age of disease onset, severity, motor ability and comorbidities across all SMA types from India. METHODS: This retrospective study involved the collection and analysis of clinical data, motor assessment scores, and SMN genetics from a cohort of 200 genetically confirmed SMA patients who were referred to our Paediatric Neuromuscular Centre over two years. RESULTS: Among the 200 subjects, 49 had SMA1, 82 had SMA2, 64 had SMA3, and 5 had SMA4. The majority of patients were male (59 %), and most hailed from the five Southern Indian states. Notably, 23 % of patients exhibited parental consanguinity. Our analysis revealed a strong correlation between the number of SMN2 copies and disease onset, as well as the achievement of developmental milestones. This trend was consistent with formal motor assessment scores and the presence and severity of co-morbidities, underscoring the pivotal role of SMN2 as a disease modifier. Additionally, we observed a small subset of patients with clinically diverse SMA types but identical SMN2 CN. INTERPRETATION: This study emphasizes the critical role of SMN2 as a disease modifier in SMA, as evidenced by its strong correlation with disease phenotype, motor scores, and the occurrence of co-morbidities. The findings underscore the importance of close monitoring and adherence to standard of care (SOC) protocols, which facilitate the proactive management of complications and co-morbidities. These practices contribute to an improved quality of life and better outcomes for SMA patients in the era of novel therapeutic approaches.