Exploring the phenotypic and genotypic spectrum of spinal muscular atrophy in Bangladeshi children.

Abstract

Spinal muscular atrophy (SMA) is a monogenic neuromuscular disorder caused by SMN1 gene deletion and classified by clinical severity. The objective of this study was to evaluate the genotypic and phenotypic spectrum in SMA in Bangladeshi children.This cross-sectional prospective study was conducted in Pediatric Neurology Department, National Institute of Neurosciences and Hospital of Bangladesh from January 2019 and December 2022. A total of sixty four cases with clinically suspected SMA were enrolled. Genetic confirmation was done using MLPA.Genetic confirmation was achieved in 48 (75%) patients. Homozygous deletion of SMN1 exons 7 and 8 was detected in 44 (68.75%) cases, while isolated exon 7 deletion was found in 4 (6.25%) cases. No deletion was identified in 16 (25%) cases. Among genetically confirmed patients, SMA type I was most common (54%), followed by type II (40%) and type III (6%). The mean age of onset was significantly earlier in SMA type I compared with types II and III (p < 0.05). A significant inverse correlation was observed between SMN2 copy number and disease severity (Spearman's rho = 0.825, p < 0.001). Most type I patients had two SMN2 copies, whereas type II and III patients predominantly had three or more copies. Respiratory complications and mortality were predominantly in type I patients. Two patients received risdiplam and two underwent gene replacement therapy (onasemnogene abeparvovec).In conclusion, A significant genotype-phenotype correlation exists between SMN2 copy number and clinical severity among Bangladeshi children with SMA. Limited access to disease-modifying therapy highlights the need for early diagnosis and improved treatment accessibility in resource-limited settings.