From the Department of Pediatrics (Dr Shapiro), Montreal Children’s Hospital, McGill University; and Department of Pediatrics (Dr Leigh), University of North Carolina School of Medicine.
CORRESPONDENCE TO: Adam J. Shapiro, MD, Department of Pediatrics, Montreal Children’s Hospital, McGill University, 2300 Tupper, D-380, Montreal, QC, H3H 1P3, Canada; e-mail: email@example.com
FINANCIAL/NONFINANCIAL DISCLOSURES: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.
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We thank Dr Reich for his interest and comments on our recent article in CHEST.1 The link between motile cilia and organ laterality defects has been firmly established since Nonaka and colleagues2 first described this in mice with dysfunction of embryonic nodal cilia. Since then, several heterotaxy mouse models have confirmed the association of dynein arm defects and embryonic nodal cilia dysmotility with primary ciliary dyskinesia (PCD).3-5 Theories on the interactions between motile nodal cilia and various forms of nonmotile cilia, both in the embryonic node6 and in the developing heart itself,7 have suggested that various signaling pathways are required for embryonic heart and visceral organ formation. Some of these signaling pathways may rely on nonmotile cilia8 or even mechanosensory functions9 of motile cilia. However, thus far in human studies, genetic mutations causing PCD with organ laterality defects are limited to those encoding for dynein arms, which are also required for embryonic nodal cilia motility.1
Human studies have failed to demonstrate PCD with cardiac defects or organ laterality defects involving deformities of the central apparatus or radial spokes (which are normally absent in embryonic nodal cilia). Of note, laterality defects have been seen in several primary ciliopathies including Bardet-Biedl syndrome, Meckel syndrome, nephronophthisis, and Jeune syndrome,10 supporting the concept that sensory cilia play a role in organ laterality. Although we are merely beginning to understand the complex interplay between motile and nonmotile cilia in congenital heart disease and organ laterality defects, we can only confirm aberrations in motile cilia as directly causing PCD with organ laterality defects.
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