Neonatal Congenital Myasthenic Syndrome Linked to CHAT Gene Variants: A Case Report and Treatment Insights

Background: Congenital myasthenic syndrome (CMS) is a rare inherited neuromuscular disorder characterized by muscle weakness and fatigue, often presenting at birth or early childhood. The condition arises from mutations af-fecting the neuromuscular junction, with an incidence of 1.5 to 9 per million. CMS is primarily classified into presynaptic, synaptic, and postsynaptic types, with mutations in the choline acetyltransferase (CHAT) gene re-sponsible for 4% to 5% of cases. The CHAT gene encodes an enzyme vital for acetylcholine synthesis, a neu-rotransmitter essential for neuromuscular communication. Mutations in CHAT disrupt acetylcholine production, impairing signal transmission at the neuromuscular junction. This report aims to present a rare case of CMS and highlight the significance of early genetic diagnosis and treatment. Case Report: We present a rare case of a newborn girl with autosomal recessive CMS caused by compound heterozygous mutations in the CHAT gene: CHAT c.1679A>G and CHAT c.287-1G>C. Born prematurely at 31 weeks gestation, she presented with severe hypotonia, respiratory failure, and absent spontaneous movements. Genetic testing confirmed CMS. Initial treatment with oral pyridostigmine was ineffective, necessitating a switch to intra-venous neostigmine, followed by continuous subcutaneous administration. This resulted in significant clinical improvement, including weaning off mechanical ventilation and achieving developmental milestones, with on-going physiotherapy. Conclusions: This case underscores the importance of early genetic testing in neonates with unexplained muscle weakness and respiratory failure. Early genetic diagnosis and personalized treatment with acetylcholinesterase inhibi-tors were key to the infant’s recovery, highlighting the potential for positive outcomes even in severe CMS cases due to ChAT mutations.