目的 探讨先天性中枢性低通气综合征（CCHS）的临床和基因变异特征。方法 分析1例首发表现为不 明原因肺动脉高压的CCHS患儿的临床资料，并总结国内外文献中CCHS病例的临床特点、致病机制和基因变异情况。 结果 11月龄女婴，主要表现为浮肿、尿少、低血压、嗜睡、发绀、抽搐及颅内压增高。B型脑利钠肽、丙氨酸氨基转移酶升 高，凝血酶原时间延长。颅脑磁共振示右侧额叶出血；超声心动图示中重度肺动脉高压。靶向捕获二代测序未发现可能的 致病基因。采用Sanger法验证示患儿PHOX 2 B基因第3外显子存在多聚丙氨酸重复扩展变异，基因型为20 / 25。患儿入院 后采用无创通气，睡眠时呼吸浅慢、微弱，伴血氧下降；血气分析提示二氧化碳潴留。随后改用夜间无创通气、降肺压药物 治疗。复查肺动脉压力明显下降，生命体征稳定。随访至24月龄，夜间只需较低压力水平的无创通气，生长发育无异常。 结论 对于不明原因的肺动脉高压伴撤机困难患儿，需警惕CCHS。疑诊者应尽早针对CCHS相关基因进行靶向捕获二代 测序及PHOX 2 B基因Sanger法验证。早期给予无创通气有望改善预后。

Objective To analyze the clinical, laboratory examination and pathogenic genes of a case of congenital central hypopnea syndrome (CCHS). Methods The clinical manifestations, laboratory examination, echocardiography, treatment and follow-up of a child with CCHS with unexplained pulmonary hypertension were collected.The genes of the child and his parents were detected by targeted capture second generation sequencing technique. The reported pathogenic genes of CCHS were verified by Sanger method, and the clinical characteristics, pathogenic mechanism and gene mutation of CCHS were summarized and discussed in combination with domestic and foreign literature. Results The main manifestations of 11 -monthold girls were edema, oliguria, hypotension, lethargy, cyanosis,convulsions; increased intracranial pressure, MRI suggested right frontal lobe hemorrhage; brain natriuretic peptide (BNP), glutamic pyruvic transaminase increased and prothrombin time prolonged;echocardiography showed moderate and severe pulmonary hypertension. No possible pathogenic genes were found in the second generation of targeted capture sequencing.After non-invasive ventilation,the breathing of the children was slow and weak during sleep, accompanied by a decrease in blood oxygen, and blood gas analysis showed carbon dioxide retention. The polyalanine repeat expansion mutation in exon 3 of PHOX 2 B was confirmed by Sanger method. Then the patients were treated with nocturnal non-invasive ventilation and antihypertensive drugs. The pulmonary artery pressure decreased significantly and the vital signs were stable.During the follow-up to 24 months old, only non-invasive ventilation with low pressure level was needed at night, and the growth and development was normal. Conclusion For children with unexplained pulmonary hypertension with difficulty in weaning, patients with suspected CCHS, should carry out the second generation of targeted capture sequencing of CCHS-related genes and Sanger verification of PHOX 2 B gene as soon as possible, which can avoid missed diagnosis of CCHS; and early non-invasive ventilation can improve the prognosis.