[Introduction] The congenital myasthenic syndrome (CMS) is a heterogenous group of inherited disorders caused by defects in various genes coding proteins involved in neuromuscular junction structure or function. Rapsyn is a 43-kDa postsynaptic protein anchoring the acetylcholin receptors (AchR) to the postsynaptic membrane of the motor endplate, mutations of which can cause endplate AchR deficiency by impairing rapsyn clustering. Here we present a patient affected with CMS due to the uncommon homozygous inframe-duplication mutation in RAPSN gene (c.1022_1042dup; p.Leu341_Ala347dup). [Case] A female infant, born full term, developed respiratory distress requiring mechanical ventilation shortly after birth. During pregnancy, pulmonary hypoplasia and bilateral club feet were noted at 32 weeks of gestation and clinical examination at birth showed bilateral ptosis, mild facial and proximal limb weakness and arthrogryposis of both hands and feet. She subsequently underwent gastrostomy and fundoplication due to sucking difficulty. Family history revealed previous pregnancy with fetal akinesia deformation sequence and death at 26 gestational age weeks. Her brain ultrasonography was normal. AChR antibody tests and EMG were not performed. Based on those clinical presentations, CMS was suspected and diagnostic exome sequencing revealed a homozygous c.1022_1042dup in the RAPSN gene. Treatment with pyridostigmine (7mg/kg/day) alleviated the ptosis and motor weakness of the patient without significant adverse effects. [Conclusion/Discussion] There have been difficulties in diagnosis of the patients with CMS due to common clinical manifestations such as congenital hypotonia and various genetic causes. With advanced genetic testing, a treatable genetic diagnosis can be made in this patient. Careful clinical history and genetic consultation is recommended in patients with congenital hypotonia to offer the better outcomes.