Clinical and genetic diversity in Iranian individuals with RAPSN-related congenital myasthenic syndrome

Congenital myasthenic syndromes (CMSs) are genetic disorders affecting motor function with variable symptoms. RAPSN -related CMS, caused by mutations in the RAPSN gene, leads to muscle weakness. Accurate diagnosis is essential for proper management. This study aims to analyze six Iranian families affected by RAPSN -CMS, focusing on clinical manifestations, genetic variants, treatment response, and outcomes. Clinical assessments, genetic analysis, and whole-exome sequencing were performed on the six families to identify RAPSN gene mutations. The study examined symptoms, disease severity, age of onset, treatment response, and outcomes. Treatment with pyridostigmine and salbutamol was given to assess its effectiveness. Three homozygous known variants in RAPSN gene were identified: c.491G > A in three families, c.264 C > A in two families, and c.-210 A > G in one family. Clinical assessments showed diversity in symptoms and treatment responses. Pyridostigmine and salbutamol treatment improved symptoms and quality of life. This study highlights the significance of molecular diagnosis for RAPSN -related congenital myasthenic syndromes (CMS) in Iran, marking the first comprehensive genetic analysis in the region. The identification of specific pathogenic variants underscores the unique genetic landscape of local patients. Furthermore, our long-term follow-up revealed variable treatment responses, emphasizing the need for personalized care strategies. The clinical variability among patients with identical mutations necessitates a multidisciplinary approach for effective management. By enhancing genetic awareness and refining follow-up methods, we aim to improve diagnosis accuracy and interventions, fostering better outcomes for affected families in the Iranian population. Highlights A comprehensive description of clinical and molecular findings in six RAPSN -related CMS patients is presented. This study represents the first comprehensive examination of RAPSN -CMS in Iran. The study contributes to the expanding spectrum of clinical and genetic variations in RAPSN , identifying previously reported variants, and supports the clinical utility of treatments like pyridostigmine.