患儿，男，3月龄，因生后持续需有创通气3个月入院。患儿胎龄33⁺⁴周，出生时无自主呼吸，予气管插管正压通气，Apgar评分1 min为3分，5、10 min均为6分。2次撤机失败，伴上睑下垂、肌张力低下、自主活动少，超声显示膈肌运动减弱，神经调节辅助通气技术监测显示膈肌电活动信号低下，无法有效触发呼吸机辅助通气。全外显子组测序发现MUSK基因存在c.2300G>A及c.2380G>A复合杂合变异，诊断为先天性肌无力综合征。口服溴吡斯的明治疗后，膈肌电活动峰值升高，但多数时间仍低，仍无法脱机。家属放弃治疗，患儿死亡。该患儿的突出表现为严重呼吸衰竭、肌无力及特异性基因变异，治疗反应不佳，预后不良。该病例提示，对于新生儿期起病、出现严重持续性呼吸衰竭伴神经肌肉受累的患儿，需警惕先天性肌无力综合征，早期基因检测有助于明确诊断，但目前治疗手段有限，需探索新的干预策略。

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.