Scope and Purpose

This site presents an overview of the syndrome known as Primary Ciliary Dyskinesia (PCD) and a description of the laboratory methodological approaches to its diagnosis. The ultrastructural characteristics of PCD are described and contrasted with pathologic changes in the conducting airway epithelium associated with acute injury caused by common viral and bacterial infections and exposure to pollutants and irritants in the ambient air. Other helpful web sites which provide a more comprehensive treatment of the clinical presentation and medical management of this disorder are listed below.

Historical Background

Primary Ciliary Dyskinesia (PCD) is an inherited syndrome which may present with a variety of seemingly disparate symptoms. The first clinical characterizations of PCD were made early in the 20th century by physicians Siewert and Kartagener. They described patients with a triad of symptoms including chronic sinusitis, bronchiectasis, and situs inversus, an anomaly in which certain organs, particularly the heart, are rotated from their normal laterality to mirror image positions. The condition became known as Kartagener's Syndrome (KS). Little was understood about the pathophysiology of this syndrome until the advent of biological electron microscopy. In the 1970s, Afzelius, Mygind, Pederson, and others described ultrastructural (electron microscopic) level anomalies of ciliary axonemes (shafts) in respiratory cilia and sperm tails of affected individuals and introduced the term Immotile Cilia Syndrome (ICS). The fine structural lesions they observed were abnormalities in the organization of axonemal dynein arms. These "arms" are appendages residing on the nine peripheral microtubular pairs comprising the ciliary axoneme and are high molecular weight ATPases which are critical to effecting ciliary beat. Because proper molecular level organization is critical to normal function, the dysmorphology of the dynein arms in patients with Immotile Cilia Syndrome was seen as the molecular level pathophysiologic basis for the adverse health effects associated with this condition. Since those first characterizations of structural anomalies in dynein arms in cilia of affected individuals, other ultrastructural defects of cilia have been described which also appear to be associated with the syndrome. Indeed, subsequent studies pointed to a heterogeneity of ultrastructural findings in Immotile Cilia Syndrome. Additional investigations of living, ciliated cells obtained from affected individuals further revealed that true immotility of the cilia was not as prevalent as an erratic, uncoordinated dyskinesia. Based on this finding, the condition is now called Primary Ciliary Dyskinesia (PCD) of which Kartagener's Syndrome is a subset.

Primary Ciliary Dyskinesia, along with cystic fibrosis and alpha-1 antitrypsin deficiency, represents one of the major inherited respiratory diseases. It is estimated to occur in about 1:16,000 Caucasians but its distribution is not limited to this racial group. Inheritance of PCD is thought to be autosomal recessive although the specific gene(s) conferring this condition remain to be identified. Because it is genetically transmitted, it is assumed that all cilia of an affected individual will exhibit the same characteristic ultrastructural lesion(s). For these reasons, examination of ciliary motility coupled with electron microscopic evaluation of ciliary/flagellar ultrastructure presently represent the standard methods of laboratory diagnosis of PCD. These analyses may be supplemented by a saccharin taste test which may further document a deficit in mucociliary clearance. To perform this test, a small saccharine tablet is placed near the anterior aspect of the inferior nasal turbinate the interval until the patient reports recognition of the sweet taste of the chemical. Individuals presenting with a life-long history of chronic sinusitis, bronchiectasis, situs inversus or dextrocardia, chronic cough, recurrent otitis media, or pneumonia are candidates for evaluation. Ciliated and flagellated cells are present in other organs and in affected individuals and their limited function may introduce additional health-related problems. Ciliated cells are integral to the transport of the ovum through the fallopian tubes in females and the molecular mechanisms conferring motility to the flagella of sperm are the same as those of cilia. Thus, adults presenting with chronic respiratory disease also may report infertility problems and should be evaluated for PCD.

Although little is known about dynein anomalies that may be associated with acute respiratory disease (e.g. infection, irritant injury, inflammation) based on our current understanding, ciliary defects in Primary Ciliary Dyskinesia appear distinctive from those associated with patterns of acute airway epithelial injury by respiratory viral and bacterial pathogenic agents and environmental irritants and pollutants. These "acquired ciliary defects" appear generally as microtubular disorganization, changes in ciliary membrane integrity, and remodeling of the normal organization of the cellular lining of the airways.

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