Secondary defects detected by transmission electron microscopy in primary ciliary dyskinesia diagnostics

Primary ciliary dyskinesia (PCD) is predominantly an autosomal recessively inherited condition that affects ~1 in 15,000 people. Diagnosis of PCD can be complex and is ordinarily based on the results of multiple investigations. These investigations include nasal nitric oxide, high-speed video microscopy, genotyping, and electron microscopy analysis of ciliary ultrastructure. A diagnosis is ultimately confirmed by the presence of a hallmark defect identified by transmission electron microscopy or biallelic variants in a known PCD gene. Secondary ciliary defects are commonly seen in samples submitted for diagnosis of PCD. Acquired secondary ciliary ultrastructural abnormalities, which are not caused by a variant in a ciliary gene, are usually transient and reversible however failure to separate primary versus secondary defects can lead to misdiagnosis. In this review, we describe causes of secondary ciliary defects, identify the ultrastructural appearances associated with secondary ciliary dyskinesia and finally suggest methods to avoid misdiagnosis of PCD due to these acquired ciliary defects.