High Prevalence of Respiratory Ciliary Dysfunction in Congenital Heart Disease Patients with Heterotaxy
Background—Patients with congenital heart disease (CHD) and heterotaxy show high postsurgical morbidity/mortality, with some developing respiratory complications. While this is often attributed to the CHD, airway clearance and left-right patterning both require motile cilia function. Thus airway ciliary dysfunction (CD) similar to that of primary ciliary dyskinesia (PCD) may contribute to increased respiratory complications in heterotaxy patients.
Methods and Results—We assessed 43 CHD patients with heterotaxy for airway CD. Videomicrocopy was used to examine ciliary motion in nasal tissue, and nasal nitric oxide (nNO) was measured, typically low with PCD. Eighteen patients exhibited CD characterized by abnormal ciliary motion and nNO below or near the PCD cut off values. Patients with CD >6 years old show increased respiratory symptoms similar to that seen in PCD. Sequencing of all 14 known PCD genes in 13 heterotaxy patients with CD, 12 without CD, 10 PCD disease-controls, and 13 healthy-controls yielded 0.769, 0.417, 1.0, and 0.077 novel variants per patient, respectively. One heterotaxy patient with CD had the PCD causing DNAI1 founder mutation. Another with hyperkinetic ciliary beat had two mutations in DNAH11, the only PCD gene known to cause hyperkinetic beat. Amongst PCD patients, two had known PCD causing CCDC39 and CCDC40 mutations.
Conclusions—Our studies show CHD patients with heterotaxy have substantial risk for CD and increased respiratory disease. Heterotaxy patients with CD were enriched for mutations in PCD genes. Future studies are needed to assess the potential benefit of prescreening and prophylactically treating heterotaxy patients for CD.
- Received November 11, 2011.
- Accepted March 6, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited