Cytoplasmic "ciliary inclusions" in isolation are not sufficient for the diagnosis of primary ciliary dyskinesia. Issue 1 (23rd September 2019)

• Record Type: Journal Article
• Authors: Vece, Timothy J.; Sagel, Scott D.; Zariwala, Maimoona A.; Sullivan, Kelli M.; Burns, Kimberlie A.; Dutcher, Susan K.; Yusupov, Roman; Leigh, Margaret W.; Knowles, Michael R.
• Is Part Of: Pediatric pulmonology. Volume 55:Issue 1(2020)
• Page Start: 130
• Page End: 135
• Publication Date: 2019-09-23
• Subjects: cilia EM -- ciliary inclusions -- primary ciliary dyskinesia; Pediatric respiratory diseases -- Periodicals; Pediatrics -- Periodicals; 618.922
• DOI: 10.1002/ppul.24528
• Languages: English
• ISSNs: 8755-6863

Abstract

Abstract: Background: The diagnosis of primary ciliary dyskinesia (PCD) is difficult and requires a combination of clinical features, nasal nitric oxide testing, cilia ultrastructural analysis by electron microscopy (EM), and genetics. A recently described cytoplasmic ultrastructural change termed "ciliary inclusions" was reported to be diagnostic of PCD; however, no supporting evidence of PCD was provided. In this study, we sought to confirm, or refute, the diagnosis of PCD in subjects with "ciliary inclusions" on EM. Methods: Six subjects from five families with previous lab reports of "ciliary inclusions" on EMs of ciliated cells were identified and evaluated at a Genetic Disorders of Mucociliary Clearance Consortium site. We performed a detailed clinical history, nasal nitric oxide measurement, genetic testing including whole‐exome sequencing (WES), and when possible, repeat ciliary EM study. Results: Only one of six subjects had multiple and persistent clinical features congruent with PCD. No subject had situs inversus. Only one of six subjects had a very low nasal nitric oxide level. No "ciliary inclusions" were found in three subjects who had a repeat ciliary EM, and ciliary axonemal ultrastructures were normal. Genetic testing, including WES, was negative for PCD‐causing genes, and for pathogenic variants in gene pathways that might cause "ciliary inclusions, " such as ciliary biogenesis. Conclusion: "Ciliary Inclusions", in isolation, are not sufficient to diagnosis PCD. If seen, additional studies should be done to pursue an accurate diagnosis.