Department of Pediatrics, University of Michigan, Ann Arbor, Michigan.
Center for Human Growth and Development, University of Michigan, Ann Arbor, Michigan.
Pediatr Pulmonol. 2020 Oct;55(10):2674-2682. doi: 10.1002/ppul.24959. Epub 2020 Jul 31.
Cilia are cell membrane-bound organelles responsible for airway mucus clearance, establishment of left-right organ asymmetry, cardiogenesis, and many other functions in utero. Phenotypic features suggestive of respiratory ciliary dyskinesia among patients with heterotaxy syndrome, defined as complex cardiovascular malformations (CVM) and situs ambiguus (SA), has not been adequately explored.
We hypothesized that there is a greater incidence of phenotypic features consistent with ciliary dyskinesia among patients with heterotaxy syndrome compared to patients with other CVM and laterality defects without heterotaxy syndrome.
Thirty six subjects were identified by medical record search and divided into four groups based on situs status and type of CVM as follows: SA and complex CVM (group 1); SA and simple CVM (group 2); situs solitus and complex CVM (group 3); and situs solitus and simple CVM (group 4). Phenotype was assessed with a clinical questionnaire, nasal nitric oxide (NO) level, and pulmonary function testing. Those with complex CVM underwent additional testing for variants in genes involved in ciliary structure and function.
The mean nasal NO level was significantly lower among all subjects with complex CVM regardless of situs anomalies (groups 1 and 3). There was no significant difference in respiratory symptoms or lung function among the four groups. No bi-allelic genetic mutations were detected among patients with complex CVM.
This study identified a relatively lower mean nasal NO level, suggestive of relative ciliary dyskinesia, among subjects with complex CVM. Pulmonary function and clinical symptoms did not reflect significant pulmonary disease among those with complex CVM.
纤毛是细胞膜结合的细胞器，负责气道黏液清除、建立左右器官不对称、心发生和许多其他功能。在具有异位症综合征的患者中，提示存在呼吸纤毛运动障碍的表型特征，其定义为复杂心血管畸形（CVM）和 situs ambiguus（SA），尚未得到充分探讨。
我们假设在具有异位症综合征的患者中，与具有其他 CVM 和无异位症综合征的侧位缺陷的患者相比，具有与纤毛运动障碍一致的表型特征的发生率更高。
通过病历搜索确定了 36 名受试者，并根据 situs 状态和 CVM 类型将其分为四组，如下所示：SA 和复杂 CVM（组 1）；SA 和简单 CVM（组 2）； situs solitus 和复杂 CVM（组 3）；和 situs solitus 和简单 CVM（组 4）。通过临床问卷、鼻一氧化氮（NO）水平和肺功能测试评估表型。具有复杂 CVM 的患者进行了额外的基因检测，以评估与纤毛结构和功能相关的基因变体。
无论 situs 异常（组 1 和 3）如何，所有患有复杂 CVM 的患者的平均鼻 NO 水平均显着降低。四组之间的呼吸道症状或肺功能无显着差异。在患有复杂 CVM 的患者中未检测到双等位基因突变。
本研究确定了具有复杂 CVM 的患者中相对较低的平均鼻 NO 水平，提示相对纤毛运动障碍。患有复杂 CVM 的患者的肺功能和临床症状并未反映出明显的肺部疾病。
