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中国循证儿科杂志

中国循证儿科杂志 ›› 2024, Vol. 19 ›› Issue (2): 126-132.DOI: 10.3969/j.issn.1673-5501.2024.02.009

• 论著 • 上一篇    下一篇

儿童原发性纤毛运动障碍13例病例系列报告

徐祝菲1,高立超1,金思怡1,姜源1,唐兰芳1,陈志敏2,王颖硕1   

  1. 浙江大学医学院附属儿童医院杭州，310057；1呼吸内科，2国家儿童健康与疾病临床医学研究中心,3 心血管内科


  • 收稿日期:2023-05-09 修回日期:2023-08-06 出版日期:2024-04-25 发布日期:2024-04-25
  • 通讯作者: 王颖硕

13 cases of primary ciliary dyskinesia in children: A case series report

XU Zhufei1,2, GAO Lichao2,3, JIN Siyi1,2, JIANG Yuan1,2, TANG Lanfang1,2, CHEN Zhimin1,2, WANG Yingshuo1,2   

  1. Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310057, China, 1 Department of Pulmonology,  2 National Clinical Research Center for Child Health, 3 Department of Cardiology
  • Received:2023-05-09 Revised:2023-08-06 Online:2024-04-25 Published:2024-04-25
  • Contact: WANG Yingshuo, email：wangyingshuo@zju.edu.cn

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摘要： 背景：原发性纤毛运动障碍(PCD)临床表现多样，容易延误诊治。 目的：分析儿童PCD的临床特征和遗传谱。 设计：病例系列报告。 方法：通过浙江大学医学院附属儿童医院病历系统收集2017年6月1日至2023年12月31日收治的PCD基因阳性患儿的性别、发病和确诊年龄、临床表现、辅助检查和基因检测结果等临床信息。检索中、英文数据库，纳入中国PCD相关基因阳性的PCD病例报告和病例系列报告，检索时间为数据库建库起至2023年12月31日，总结中国PCD病例的临床表型、基因型及其在中国各地区分布。 主要结局指标：中国PCD患儿临床特征和基因型。 结果：13例PCD患儿进入本文分析，男7例（53.8%），女6例。中位发病年龄为9.0岁（3 d至14.3岁），中位诊断年龄为11.3岁（24 d至14.9岁）。临床主要表现为咳嗽伴咳痰11例（84.6%），鼻窦炎10例（76.9%），发热7例（53.8%），支气管扩张、内脏转位和肺不张各6例（46.2%），鼻塞、流脓涕和符合Kartagener综合征各4例（30.8%）。13例患儿共检测到8个基因的突变，其中DNAH11基因突变4例（28.6%），DNAH5基因突变3例（21.4%），CCDC114、DNAH9、DNAAF3、ODAD1、CCNO和RSPH1基因突变各1例；23个双等位基因突变位点，ACMG判定为致病8个，可能致病7个，意义未明（VUS）8个；对8个VUS位点进一步行蛋白功能软件预测均为有害。文献复习72篇病例报告和病例系列报告进入本文分析，PCD 391例，相关基因阳性316例，共检测出PCD相关基因40个。基因变异位点频率排名最高的前5位为DNAH5（21.2%）、DNAH11（17.7%）、CCDC40（7.9%）、HYDIN（6.6%）、CCNO（6.0%）。PCD病例临床表型最常见的是长期咳嗽伴咳痰（91.3%）、慢性鼻窦炎（87.0%）、支气管扩张（70.6%）和肺功能异常（64.2%）。北京、上海和浙江地区均以DNAH11和DNAH5基因变异为主，重庆以HYDIN基因变异（19.1%）为主，广东以DNAH1基因变异（22.2%）为主，广西以RSPH4A(13.3%)、HYDIN（10.0%）、DNAH11（10.0%）、CCDC40（10.0%）和ZMYND10（10.0%）基因变异为主，湖南以DNAH5（18.2%）和DNAAF4（13.6%）基因变异为主。 结论：中国最常见的PCD相关基因是DNAH11和DNAH5，临床表型以长期咳嗽伴咳痰、慢性鼻窦炎等呼吸道症状为主。

关键词: 原发性纤毛运动障碍, 儿童, 基因, 中国

Abstract: Background：The clinical manifestations of primary ciliary dyskinesia(PCD) are relatively diverse and often undiagnosed or delayed in diagnosis and treatment. Objective：To investigate the clinical characteristics and genetic spectrum of primary ciliary dyskinesia in children. Design：Case series study. Methods：The medical records system was used to collect clinical information on PCD gene-positive children admitted to Children's Hospital, Zhejiang University School of Medicine between June 1, 2017 and December 31, 2023. This information included gender, age of onset and diagnosis, clinical manifestations, auxiliary examinations, and genetic testing results. A search of Chinese and English databases was conducted to include case series reports of PCD with PCD-related gene positivity in China. The search period spanned from the establishment of the database until December 2023. This study summarises the clinical phenotypes and genotypes of PCD cases in China, as well as their distribution across various regions of the country. Main outcome measures：Clinical characteristics and genetic spectrum of children in China. Results：Thirteen children diagnosed with PCD were analysed, comprising of 7 boys (53.8%) and 6 girls. The median age of onset was 9.0 years (ranging from 3 days to 14.3 years), and the median age of diagnosis was 11.3 years (ranging from 24 days to 14.9 years). The study found that the most common clinical manifestations were cough and expectoration in 11 cases (84.6%), sinusitis in 10 cases (76.9%), fever in 7 cases (53.8%), bronchiectasis, visceral transposition, and atelectasis in 6 cases each (46.2%), nasal congestion, purulent nasal discharge, and Kartagener syndrome in 4 cases each (30.8%). Thirteen children were found to have eight gene mutations. Of the 23 double allelic gene mutation sites identified, 4 cases were related to DNAH11 gene mutation (28.6%), 3 cases to DNAH5 gene mutation (21.4%), and 1 case each to CCDC114, DNAH9, DNAAF3, ODAD1, CCNO, and RSPH1 gene mutations. ACMG classified 8 mutations as pathogenic, 7 as possibly pathogenic, and 8 as variants of uncertain significance (VUS). All 8 VUS sites were predicted to be deleterious by protein function software prediction. This analysis includes seventy-two case series reports or case reports including 391 PCD cases and 316 gene-positive cases. A total of 40 PCD-related genes were detected. The top five most frequent gene mutation sites were DNAH5 (21.2%), DNAH11 (17.7%), CCDC40 (7.9%), HYDIN (6.6%), and CCNO (6.0%). The most frequent clinical phenotypes of PCD cases were chronic cough and expectoration (91.3%), chronic sinusitis (87.0%), bronchiectasis (70.6%), and abnormal lung function (64.2%). In Beijing, Shanghai, and Zhejiang province, the main gene variations were DNAH11 and DNAH5. In Chongqing, the main variation was HYDIN (19.1%), while in Guangdong province, it was DNAH1 (22.2%). In Guangxi Zhuang Autonomous Region, the main variations were RSPH4A (13.3%)、HYDIN (10.0%)、DNAH11 (10.0%)、CCDC40 (10.0%), and ZMYND10 (10.0%). In Hunan province, the main variations were DNAH5 (18.2%) and DNAAF4 (13.6%). Conclusion：In China, the most commonly occurring genes related to PCD are DNAH11 and DNAH5. The main clinical symptoms include respiratory issues, such as persistent coughing, expectoration, and chronic sinusitis.

Key words: Primary ciliary dyskinesia, Children, Gene, China