Primary ciliary dyskinesia: improving the diagnostic approach

Abstract

Purpose of review: The diagnosis of primary ciliary dyskinesia (PCD) has relied on analysis of ciliary motility and ultrastructure; however, these tests are not readily available and have not been standardized. Consequently, the diagnosis of PCD may be delayed or missed or made incorrectly. This review outlines the potential utility of new diagnostic tests, including measurement of nasal nitric oxide production and systematic analysis for mutations in genes encoding ciliary proteins.

Recent findings: Clinical manifestations of PCD have been expanded to include neonatal respiratory distress and heterotaxy. Measurement of nasal nitric oxide has emerged as a useful screening test for PCD based on the very low levels in PCD (approximately 1/10 of normal values). Genetic testing is emerging for PCD and demonstrates extensive genetic heterogeneity. Some genes and gene mutations involved in PCD have been defined. Approximately one-third of PCD cases have identifiable gene mutations in one of six different genes. An international effort is focused on defining PCD-causing defects in other genes.

Summary: The incorporation of nasal nitric oxide measurement as a screening test to define probable PCD cases and gene mutation analysis to make a definitive diagnosis of PCD should enhance diagnostic evaluation of PCD.

Figure 1

Schematic showing 9+2 configuration in the cross-section of an axoneme: All of the axonemal components are labeled. Peripheral microtubules are arranged in 9 doublets (two microtubule components, A and B, are merged) with dynein arms arising from the A component. In the center is a pair of microtubules (C1 and C2). Genes mutated in human PCD are shown and linked with the corresponding axonemal structure that is involved. * Mutations seen in patient with normal dynein arms ** Encodes cytoplasmic protein that is required for ODA assembly, and mutations seen in patients with defects involving both outer and inner dynein arms