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Abstract：
Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder characterized by hypoventilation due to impaired breathing control by the central nervous system and other symptoms of autonomic dysfunction. Mutations in paired-like homeobox 2 B (PHOX2B) are responsible for most cases of CCHS. Patients with CCHS have various phenotypes and severities, making the diagnosis difficult. This study aimed to present a comprehensive single-center experience of patients with CCHS, including key clinical features, treatment strategies, and outcomes. A retrospective chart review was performed for patients diagnosed with CCHS between January 2001 and July 2023 at Seoul National University Children\'s Hospital. Finally, we selected 24 patients and collected their demographic data, genotypes, ventilation methods, and clinical features related to autonomic dysfunction. The relationship between the clinical manifestations and genotypes was also examined. All patients used home ventilators, and tracheostomy was performed in 87.5% of patients. Fifteen (62.5%) patients had constipation and nine (37.5%) were diagnosed with Hirschsprung disease. Arrhythmia, endocrine dysfunction, and subclinical hypothyroidism were present in nine (37.5%), six patients (25.0%), and two patients (16.7%), respectively. A significant number of patients exhibited neurodevelopmental delays (19 patients, 79.2%). There was a correlation between the phenotype and genotype of PHOX2B in patients with CCHS. (r = 0.71, p < 0.001). Conclusion: There was a positive correlation between paired-like homeobox 2 B mutations (especially the number of GCN repeats in the polyalanine repeat mutations sequence) and clinical manifestations. This study also demonstrated how initial treatment for hypoventilation affects neurodevelopmental outcomes in patients with CCHS. What is Known: • Congenital central hypoventilation syndrome is a rare genetic disorder characterized by hypoventilation and dysfunction of autonomic nervous system. • The disease-defining gene of CCHS is PHOX2B gene - most of the cases have heterozygous PARMs and the number of GCN triplets varies among the patients(20/24 - 20/33). What is New: • We have noted in the Korean patients with CCHS that there is a correlation between genotype (number of GCN repeats) and severity of phenotype. • National support for rare diseases allowed for a prompter diagnosis of patients with CCHS in Korean population.
摘要：
先天性中枢通气不足综合征（CCHS）是一种罕见的遗传性疾病，其特征是由于中枢神经系统呼吸控制受损以及其他自主神经功能障碍的症状而导致的通气不足。配对样同源异型盒2B(PHOX2B)中的突变是大多数CCHS病例的原因。CCHS患者有不同的表型和严重程度，使诊断变得困难。本研究旨在提供CCHS患者的全面单中心体验，包括关键的临床特征，治疗策略,和结果。对2001年1月至2023年7月在首尔国立大学儿童医院诊断为CCHS的患者进行了回顾性图表回顾。最后,我们选择了24名患者并收集了他们的人口统计数据，基因型，通风方法,以及与自主神经功能障碍相关的临床特征。还检查了临床表现与基因型之间的关系。所有病人都使用家用呼吸机,87.5%的患者进行了气管切开术。15例（62.5％）患者便秘，9例（37.5％）被诊断为Hirschsprung病。心律失常,内分泌功能障碍,亚临床甲状腺功能减退症有9例（37.5%），6名患者(25.0%)，和两名患者(16.7%)，分别。相当数量的患者表现出神经发育迟缓(19例患者，79.2%）。CHS患者PHOX2B的表型和基因型之间存在相关性。(r=0.71,p<0.001)。结论:配对样同源异型盒2B突变(尤其是多聚丙氨酸重复序列中GCN重复序列的数量)与临床表现呈正相关。这项研究还证明了低通气的初始治疗如何影响CCHS患者的神经发育结果。已知:•先天性中枢换气不足综合征是一种罕见的遗传性疾病,其特征在于换气不足和自主神经系统功能障碍。•CCHS的疾病定义基因是PHOX2B基因-大多数病例具有杂合的PARM，并且GCN三胞胎的数量因患者而异（20/24-20/33）。新增内容:•我们在患有CCHS的韩国患者中注意到基因型(GCN重复的数量)与表型的严重程度之间存在相关性。•国家对罕见疾病的支持允许对韩国人群中的CCHS患者进行更迅速的诊断。
