Retrospective analysis of spinal muscular atrophy in tunisian population: phenotypic-genotypic associations and considerations for therapeutic advancement.

This study retrospectively analyzed 97 Tunisian Spinal Muscular Atrophy (SMA) patients (2008-2024), characterizing their phenotypes, diagnosis age, and consanguinity alongside copy number variations of SMN1, SMN2, NAIP, p44, and H4F5. SMA-I was the most prevalent phenotype (61.86%). We notice a significant male predominance with significant late age of diagnosis. Consanguinity was remarkably high (73.53%) and strongly associated with severe form SMA-I. Genetic analysis confirmed SMN2 and NAIP as key modifiers, where lower copy numbers correlated with increased severity and respiratory complications. With 98% of patients carrying ≥ 2 SMN2 copies, most are eligible for splicing-modifier therapies. Additionally, the prevalence of early-onset SMA-I underscores a promising perspective for gene replacement therapy before irreversible motor neuron loss occurs. SMN2 and NAIP are vital prognostic markers in Tunisia. High consanguinity and gender-based diagnostic delays necessitate urgent newborn screening and early genetic intervention to optimize modern therapy efficacy.