A 20-year experience of electron microscopy in the diagnosis of primary ciliary dyskinesia

Abstract

Transmission electron microscopy (TEM) analysis of ciliary ultrastructure is classically used for the diagnosis of primary ciliary dyskinesia (PCD). We report our extensive experience of TEM analysis in a large series of patients in order to evaluate its feasibility and results.TEM analysis performed in 1,149 patients with suspected PCD was retrospectively reviewed. Biopsies (1,450) were obtained from nasal (44%) or bronchial (56%) mucosa in children (66.5%) and adults (33.5%).TEM analysis was feasible in 71.4% of patients and showed a main defect suggestive of PCD in 29.9%. TEM was more feasible in adults than in children, regardless of the biopsy site. Main defects suggestive of PCD were found in 76.9% of patients with sinopulmonary symptoms and in only 0.4% of patients with isolated upper and 0.4% with isolated lower respiratory tract infections. The defect pattern was similar in children and adults, involving dynein arms (81.2%) or central complex (CC) (18.8%). Situs inversus was never observed in PCD patients with CC defect. Kartagener syndrome with normal ciliary ultrastructure was not an exceptional condition (10.2% of PCD).In conclusion, TEM analysis is feasible in most patients and is particularly useful for PCD diagnosis in cases of sinopulmonary syndrome of unknown origin.

Static respiratory cilia associated with mutations in Dnahc11/DNAH11: A mouse model of PCD

“…Ultrastructural defects in the axoneme underlie a significant proportion of PCD cases, most frequently defects of dynein arms [Bush et al, 2007]. However, at least 10% of PCD patients have normal ciliary ultrastructure [Greenstone et al, 1983;Jorissen et al, 2000;Papon et al, 2010] and diagnosis often proves particularly challenging in these patients. Two mutations in the dynein heavy chain gene DNAH11 (MIM# 603339) were recently described in a family with PCD associated with hyperkinetic cilia but normal ultrastructure [Schwabe et al, 2008].…”

Standardizing Nasal Nitric Oxide Measurement as a Test for Primary Ciliary Dyskinesia

“…The diagnosis of PCD has traditionally been made by demonstration of ciliary ultrastructural or functional abnormalities, using transmission electron microscopy (EM) or video microscopy of airway epithelial biopsies (4,5), although these approaches have many limitations and are dependent on adequate sample processing and expertise to interpret axonemal defects or abnormal ciliary activity (6). Genetic testing of the 21 known genes associated with PCD is emerging, but only a minority of individuals can currently be identified using commercially available tests (2).…”

Diagnostic Methods in Primary Ciliary Dyskinesia

“…The most common ultrastructural defects are: ODA-defects (25-50%) and combined IDA-and M a n u s c r i p t ODA-defects (25-50%) [47,[57][58][59] (figure 4). IDA defects associated with microtubular disorganisation occur in 15% of PCD, but isolated IDA defects as a cause of PCD are controversial particularly as no mutations have been identified in IDA proteins.…”

“…National collaborations are contributing to improved diagnostic management in a number of individual countries including France [58,106], and the United Kingdom [17,107].…”