Genetic disorders of surfactant dysfunction are a rare cause of chronic, progressive or refractory respiratory failure in term and preterm infants. This review explores genetic mechanisms underpinning surfactant dysfunction, highlighting specific surfactant-associated genes including SFTPB, SFTPC, ABCA3, and NKX2.1. Pathogenic variants in these genes contribute to a range of clinical presentations and courses, from neonatal hypoxemic respiratory failure to childhood interstitial lung disease and even adult-onset pulmonary fibrosis. This review emphasizes the importance of early recognition, thorough phenotype assessment, and assessment of variant functionality as essential prerequisites for treatments including lung transplantation. We explore emerging treatment options, including personalized pharmacological approaches and gene therapy strategies. In conclusion, this comprehensive review offers valuable insights into the pathogenic mechanisms of genetic disorders of surfactant dysfunction, genetic fundamentals, available and emerging therapeutic options, and underscores the need for further research to develop personalized therapies for affected infants and children.

表面活性剂功能障碍的遗传性疾病是足月儿和早产儿慢性、进行性或难治性呼吸衰竭的罕见原因。本综述探讨了表面活性剂功能障碍的遗传机制，重点介绍了特定的表面活性剂相关基因，包括SFTPB、SFTPC、ABCA3和NKX2.1 。这些基因的致病变异导致一系列临床表现和病程，从新生儿低氧性呼吸衰竭到儿童间质性肺病，甚至成人发病的肺纤维化。本综述强调了早期识别、彻底的表型评估和变异功能评估的重要性，作为包括肺移植在内的治疗的基本先决条件。我们探索新兴的治疗方案，包括个性化药理学方法和基因治疗策略。总之，这篇全面的综述为表面活性剂功能障碍遗传性疾病的致病机制、遗传基础、现有和新兴的治疗选择提供了有价值的见解，并强调需要进一步研究为受影响的婴儿和儿童开发个性化疗法。