Lee Peilin, Su Yi-Ning, Yu Chong-Jen, Yang Pan-Chyr, Wu Huey-Dong
Center of Sleep Disorder, National Taiwan University Hospital, Taipei, Taiwan.
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Chest. 2009 Feb;135(2):537-544. doi: 10.1378/chest.08-1664.
Congenital central hypoventilation syndrome (CCHS) is characterized by compromised chemoreflexes resulting in sleep hypoventilation. We report a Chinese family with paired-like homeobox 2B (PHOX2B) mutation-confirmed CCHS, with a clinical spectrum from newborn to adulthood, to increase awareness of its various manifestations.
After identifying central hypoventilation in an adult man (index case), clinical evaluation was performed on the complete family, which consisted of the parents, five siblings, and five offspring. Pulmonary function tests, overnight polysomnography, arterial blood gas measurements, hypercapnia ventilatory response, and PHOX2B gene mutation screening were performed on living family members. Brain MRI, 24-h Holter monitoring, and echocardiography were performed on members with clinically diagnosed central hypoventilation.
The index patient and four offspring manifested clinical features of central hypoventilation. The index patients had hypoxia and hypercapnia while awake, polycythemia, and hematocrit levels of 70%. The first and fourth children had frequent cyanotic spells, and both died of respiratory failure. The second and third children remained asymptomatic until adulthood, when they experienced impaired hypercapnic ventilatory response. The third child had nocturnal hypoventilation with nadir pulse oximetric saturation of 59%. Adult-onset CCHS with PHOX2B gene mutation of the + 5 alanine expansions were confirmed in the index patient and the second and third children. The index patient and the third child received ventilator support system bilevel positive airway pressure treatment, which improved the hypoxemia, hypercapnia, and polycythemia without altering their chemosensitivity.
Transmission of late-onset CCHS is autosomal-dominant. Genetic screening of family members of CCHS probands allows for early diagnosis and treatment.
先天性中枢性低通气综合征（CCHS）的特征是化学反射受损，导致睡眠时低通气。我们报告了一个经成对样同源盒2B（PHOX2B）突变确诊的CCHS中国家系，其临床表现涵盖从新生儿到成年期，以提高对其各种表现的认识。
在一名成年男性（索引病例）被诊断为中枢性低通气后，对整个家系进行了临床评估，该家系包括父母、五个兄弟姐妹和五个后代。对在世的家庭成员进行了肺功能测试、夜间多导睡眠图监测、动脉血气测量、高碳酸血症通气反应以及PHOX2B基因突变筛查。对临床诊断为中枢性低通气的成员进行了脑部MRI、24小时动态心电图监测和超声心动图检查。
索引患者和四个后代表现出中枢性低通气的临床特征。索引患者清醒时存在低氧血症和高碳酸血症、红细胞增多症，血细胞比容水平达70%。第一个和第四个孩子频繁出现发绀发作，均死于呼吸衰竭。第二个和第三个孩子直到成年都无症状，成年后出现高碳酸血症通气反应受损。第三个孩子夜间低通气，脉搏血氧饱和度最低点为59%。索引患者以及第二个和第三个孩子被确诊为携带PHOX2B基因+5丙氨酸扩展突变的成年发病型CCHS。索引患者和第三个孩子接受了双水平气道正压通气支持系统治疗，这改善了低氧血症、高碳酸血症和红细胞增多症，但未改变他们的化学敏感性。
迟发性CCHS的遗传方式为常染色体显性遗传。对CCHS先证者的家庭成员进行基因筛查有助于早期诊断和治疗。
