Parrey_2025_Am.J.Neurodegener.Dis_14_108

BACKGROUND: Congenital myasthenic syndromes (CMS) are rare inherited disorders of neuromuscular transmission caused by mutations in presynaptic, synaptic, or postsynaptic components. They usually manifest in childhood with fatigability, ptosis, ophthalmoplegia, and generalized weakness, but late presentations also occur. CASE SUMMARY: We report a 20-year-old male presenting with heart failure and respiratory failure who was found to have a heterozygous AGRN gene mutation (c.4319>T; p. Pro1440Leu). Clinical features included muscle wasting, weakness, restricted gaze, and respiratory compromise requiring ICU care. Genetic sequencing confirmed AGRN-related CMS. Management included ICU support, pyridostigmine trial, heart failure therapy, salbutamol, and fluoxetine with improvement. DISCUSSION: Diagnosis of CMS requires clinical suspicion, characteristic electrophysiology, and genetic confirmation. Treatment varies with subtype; AGRN-related CMS responds variably to salbutamol and ephedrine, while cholinesterase inhibitors may be ineffective. Prognosis depends on timely diagnosis and management.