Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 108 Pyeong-dong, Jongno-gu, Seoul, Republic of Korea 110-746.
Eur J Pediatr. 2011 Oct;170(10):1267-71. doi: 10.1007/s00431-011-1434-5. Epub 2011 Mar 4.
Congenital central hypoventilation syndrome (CCHS), also known as Ondine's curse, is characterized by idiopathic failure of autonomic breathing and is often associated with neurocristopathies such as Hirschsprung disease (HSCR). CCHS is caused by mutations in the paired-like homeobox 2B (PHOX2B) gene, often manifest as polyalanine repeat expansions. Herein, we report the cases of two unrelated Korean patients with Ondine-Hirschsprung disease. The patient's clinical manifestations were apnea and cyanosis requiring immediate endotracheal intubation, recurrent hypoventilation with hypercapnia, hypoxia after ventilator removal, and abdominal distension since birth. Intestinal biopsies were performed and the absence of ganglion cells in the colon was consistent with HSCR. We performed direct sequencing analysis in the PHOX2B and RET genes and fluorescence polymerase chain reaction in order to determine the polyalanine tract expansion in exon 3 of the PHOX2B gene. Expansion mutations were detected in both patients; one had 20/24 repeats and the other had 20/27 repeats. The 20/24 genotype has not been previously described in severe CCHS phenotypes and associated HSCR. We believe that the information in this report will improve our understanding of the phenotypic and genotypic heterogeneities of CCHS and HSCR.
先天性中枢性肺泡换气不足综合征（CCHS），也被称为“奥丁诅咒”，其特征是自主呼吸功能障碍，常与神经嵴细胞病变有关，如先天性巨结肠（HSCR）。CCHS 是由配对同源框 2B（PHOX2B）基因突变引起的，常表现为多聚丙氨酸重复扩展。在此，我们报告了两例韩国无关的“奥丁-先天性巨结肠”患者病例。患者的临床表现为呼吸暂停和发绀，需要立即行气管插管，反复出现低通气伴高碳酸血症、呼吸机撤离后缺氧以及出生后腹胀。进行了肠活检，结肠中无神经节细胞，符合先天性巨结肠的特征。我们对 PHOX2B 和 RET 基因进行了直接测序分析，并对 PHOX2B 基因外显子 3 中的多聚丙氨酸重复进行了荧光聚合酶链反应，以确定其扩展情况。在两名患者中均检测到扩展突变，一名患者有 20/24 个重复，另一名患者有 20/27 个重复。20/24 基因型以前未在严重 CCHS 表型和相关 HSCR 中描述过。我们相信，本报告中的信息将有助于我们更好地理解 CCHS 和 HSCR 的表型和基因型异质性。
