Magalhães Joana, Madureira Núria, Medeiros Rita, Fernandes Paula C, Oufadem Myriam, Amiel Jeanne, Estêvão M Helena, Reis M Guilhermina
Departamento da Criança e Adolescente, Centro Hospitalar do Porto, Largo Professor Abel Salazar, 4099-001, Porto, Portugal,
Sleep Breath. 2015 Mar;19(1):55-60. doi: 10.1007/s11325-014-0996-7. Epub 2014 May 4.
Congenital central hypoventilation syndrome (CCHS) is a rare lifelong disorder characterized by an abnormal ventilatory response with persistent hypercapnia and hypoxia, which worsen during sleep. About 90 % of CCHS individuals are heterozygous for a mutation in the exon 3 of the PHOX2B gene. With higher awareness and better diagnostic tools, cases are identified in late childhood and adulthood, often with distinct mutations.
The authors present a 4-year-old girl admitted to the intensive care unit at 9, 11 and 13 months suffering from severe hypercapnic respiratory failure during viral respiratory infections. Hypercapnia during sleep improved with wakefulness. CCHS was confirmed genetically (heterozygous insertion of an adenine at position 23, leading to a premature stop codon in exon 1 of the PHOX2B gene). The parents' DNA showed no PHOX2B mutations. Hypoventilation was observed by polysomnography, with no autonomic response to declining oxygen or increasing carbon dioxide values. A subsequent sleep study showed less hypoxia and hypercapnia. The patient has been on non-invasive ventilation during sleep, showing good growth and neurocognitive development.
A greater awareness is required to diagnose late-onset CCHS. A respiratory infection can trigger the disease, with a significant difference in CO2 between sleep and wakefulness as the warning signal. Given the clinical suspicion, a genetic study should be performed. Polysomnography is essential for patient characterization. Follow-up and ventilator support adjustment prevent serious hypoxia and hypercapnia, which impair cardiovascular and neurocognitive functions. This patient's mutation has not been previously described; hence, clinical evolution cannot be predicted.
先天性中枢性低通气综合征（CCHS）是一种罕见的终身性疾病，其特征为通气反应异常，伴有持续性高碳酸血症和低氧血症，且在睡眠期间会加重。约90%的CCHS患者为PHOX2B基因第3外显子突变的杂合子。随着认识的提高和诊断工具的改进，在儿童晚期和成年期也能确诊病例，且常伴有不同的突变。
作者介绍了一名4岁女孩，在9个月、11个月和13个月时因病毒性呼吸道感染入住重症监护病房，患有严重的高碳酸血症呼吸衰竭。睡眠期间的高碳酸血症在清醒时有所改善。通过基因检测确诊为CCHS（PHOX2B基因第1外显子23位杂合插入一个腺嘌呤，导致提前出现终止密码子）。父母的DNA未显示PHOX2B突变。通过多导睡眠图观察到通气不足，对氧含量下降或二氧化碳值升高无自主反应。随后的睡眠研究显示低氧血症和高碳酸血症有所减轻。该患者在睡眠期间一直使用无创通气，生长和神经认知发育良好。
需要提高对迟发性CCHS的诊断意识。呼吸道感染可引发该病，睡眠和清醒时二氧化碳水平的显著差异是警示信号。鉴于临床怀疑，应进行基因研究。多导睡眠图对于患者特征描述至关重要。随访和调整呼吸机支持可预防严重的低氧血症和高碳酸血症，这些会损害心血管和神经认知功能。该患者的突变此前未被描述；因此，无法预测临床病程。
