A case of neonatal congenital myasthenic syndrome caused by MUSK gene variants

A 3-month-old male infant was admitted because he had required continuous invasive ventilation since birth. He was delivered at 33⁺⁴ weeks' gestation without spontaneous respiration;endotracheal intubation with positive-pressure ventilation was initiated, and Apgar scores were 3, 6, and 6 at 1, 5, and 10 minutes, respectively. Two attempts to wean from mechanical ventilation failed. Clinical findings included ptosis, hypotonia, and reduced spontaneous movements. Ultrasonography showed decreased diaphragmatic motion. Monitoring with neurally adjusted ventilatory assist showed low electrical activity of the diaphragm, insufficient to reliably trigger ventilator assistance. Whole-exome sequencing identified compound heterozygous variants (c.2300G>A and c.2380G>A) in the MUSK gene, confirming the diagnosis of congenital myasthenic syndrome. After oral pyridostigmine, the peak value of electrical activity of the diaphragm increased, but it remained low for most of the time, and the infant remained ventilator-dependent. The family elected to discontinue active treatment, and the infant died. This case is characterized by severe respiratory failure, muscle weakness, and specific causative gene variants, with limited treatment response and poor prognosis. Congenital myasthenic syndrome should be considered in neonates with early-onset, persistent, severe respiratory failure accompanied by neuromuscular involvement. Early genetic testing facilitates a definitive diagnosis, but current therapeutic options are limited, underscoring the need for new interventions.