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 affecting 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 responsible for 4% to 5% of cases. The CHAT gene encodes an enzyme vital for acetylcholine synthesis, a neurotransmitter 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 intravenous neostigmine, followed by continuous subcutaneous administration. This resulted in significant clinical improvement, including weaning off mechanical ventilation and achieving developmental milestones, with ongoing 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 inhibitors were key to the infant's recovery, highlighting the potential for positive outcomes even in severe CMS cases due to ChAT mutations.