Abstract 15746: Airway Ciliary Dysfunction in Patients with Transposition of the Great Arteries
Background: Transposition of the great arteries (TGA) is a congenital heart defect with the aorta transposed anteriorly and inserted into the morphological right ventricle (D-TGA). When associated with ventricle inversion (L-TGA), it is considered a laterality defect, given both atrioventricular and ventriculoarterial discordance. However, as mouse heterotaxy models can exhibit isolated D-TGA, and patients with D-TGA can have heterotaxy mutations, this would suggest both L/D-TGA are laterality defects. We recently showed heterotaxy patients have a high incidence of airway ciliary dysfunction (CD) similar to primary ciliary dyskinesia (PCD), a reflection of the requirement for motile cilia in left-right patterning. Therefore, we hypothesize TGA may be associated with airway CD and arise from mutations in cilia-related PCD genes.
Methods: We recruited 39 patients with isolated TGA and 4 with TGA and other laterality defects (19.5±15yrs, 62.8% male). Ciliary function was assessed by measuring nasal nitric oxide (nNO), typically low with PCD, and nasal scrapes were obtained for assessing ciliary motion by videomicroscopy. Blood was obtained for whole-exome sequencing.
Results: Forty-three patients with TGA were enrolled in the study; 20 with D-TGA and 13 with L-TGA. Videomicroscopy identified 14/36 (38.9%; 6 with D-TGA ) with abnormal ciliary motion and 7/41 (17%; 3 with D-TGA) were found to have low nNO. Two (1 with D-TGA) had both abnormal ciliary motion and low nNO. The patient with L-TGA had heterotaxy, and showed PCD symptoms - newborn respiratory distress, otitis media, and recurrent pneumonia. Exome sequencing is in progress to interrogate for disease causing variants in PCD genes.
Conclusions: We observed 38.9% of TGA patients had CD characterized by abnormal ciliary motion, two of which also had low nNO. Surprisingly, five patients had low nNO with normal ciliary motility. No difference was observed in the incidence of ciliary dysmotility or low nNO with L vs. D-TGA. These findings indicate that L or D-TGA could arise from a common etiology involving motile cilia defects. Discordance in cilia motion defect with low nNO would suggest that CD in TGA patients might differ from that of heterotaxy or classic PCD.
- © 2012 by American Heart Association, Inc.