BACKGROUND: Patients with congenital heart disease (CHD) and heterotaxy show 
high postsurgical morbidity/mortality, with some developing respiratory 
complications. Although this finding 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; nNO level is typically low with PCD. Eighteen 
patients exhibited CD characterized by abnormal ciliary motion and nNO levels 
below or near the PCD cutoff values. Patients with CD aged >6 years show 
increased respiratory symptoms similar to those 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 2 
mutations in DNAH11, the only PCD gene known to cause hyperkinetic beat. Among 
PCD patients, 2 had known PCD causing CCDC39 and CCDC40 mutations.
CONCLUSIONS: Our studies show that 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.