Kennedy Marcus P, Omran Heymut, Leigh Margaret W, Dell Sharon, Morgan Lucy, Molina Paul L, Robinson Blair V, Minnix Susan L, Olbrich Heike, Severin Thomas, Ahrens Peter, Lange Lars, Morillas Hilda N, Noone Peadar G, Zariwala Maimoona A, Knowles Michael R
University of North Carolina, Chapel Hill, NC, USA.
Circulation. 2007 Jun 5;115(22):2814-21. doi: 10.1161/CIRCULATIONAHA.106.649038. Epub 2007 May 21.
Primary ciliary dyskinesia (PCD) is a recessive genetic disorder that is characterized by sinopulmonary disease and reflects abnormal ciliary structure and function. Situs inversus totalis occurs in approximately 50% of PCD patients (Kartagener's syndrome in PCD), and there are a few reports of PCD with heterotaxy (situs ambiguus), such as cardiovascular anomalies. Advances in diagnosis of PCD, such as genetic testing, allow the systematic investigation of this association.
The prevalence of heterotaxic defects was determined in 337 PCD patients by retrospective review of radiographic and ultrasound data. Situs solitus (normal situs) and situs inversus totalis were identified in 46.0% and 47.7% of patients, respectively, and 6.3% (21 patients) had heterotaxy. As compared with patients with situs solitus, those with situs abnormalities had more ciliary outer dynein arm defects, fewer inner dynein arm and central apparatus defects (P<0.001), and more mutations in ciliary outer dynein arm genes (DNAI1 and DNAH5; P=0.022). Seven of 12 patients with heterotaxy who were genotyped had mutations in DNAI1 or DNAH5. Twelve patients with heterotaxy had cardiac and/or vascular abnormalities, and most (8 of 12 patients) had complex congenital heart disease.
At least 6.3% of patients with PCD have heterotaxy, and most of those have cardiovascular abnormalities. The prevalence of congenital heart disease with heterotaxy is 200-fold higher in PCD than in the general population (1:50 versus 1:10 000); thus, patients with PCD should have cardiac evaluation. Conversely, mutations in genes that adversely affect both respiratory and embryological nodal cilia are a significant cause of heterotaxy and congenital heart disease, and screening for PCD is indicated in those patients.
原发性纤毛运动障碍（PCD）是一种隐性遗传病，其特征为鼻窦肺部疾病，反映了纤毛结构和功能异常。约50%的PCD患者会出现全内脏反位（PCD中的卡塔格内综合征），也有少数关于PCD合并内脏异位（脏器位置不明确）的报道，如心血管异常。PCD诊断技术的进步，如基因检测，使得对这种关联的系统研究成为可能。
通过回顾性分析X线和超声数据，确定了337例PCD患者内脏异位缺陷的患病率。分别有46.0%和47.7%的患者被确定为正位（正常位置）和全内脏反位，6.3%（21例患者）有内脏异位。与正位患者相比，内脏位置异常的患者有更多的纤毛外动力蛋白臂缺陷，更少的内动力蛋白臂和中央微管缺陷（P<0.001），以及更多的纤毛外动力蛋白臂基因（DNAI1和DNAH5）突变（P=0.022）。12例进行基因分型的内脏异位患者中有7例在DNAI1或DNAH5基因存在突变。12例内脏异位患者有心脏和/或血管异常，大多数（12例中的8例）患有复杂先天性心脏病。
至少6.3%的PCD患者有内脏异位，其中大多数有心血管异常。PCD合并内脏异位的先天性心脏病患病率比普通人群高200倍（1:50对1:10000）；因此，PCD患者应进行心脏评估。相反，对呼吸和胚胎学节点纤毛均产生不利影响的基因突变是内脏异位和先天性心脏病的重要原因，这些患者应进行PCD筛查。
