FINAL DIAGNOSIS: CILIARY MOTILITY DISORDER CONSISTENT WITH IMMOTILE CILIA SYNDROME
Disorders of ciliary motility are a heterogenous group of inherited disorders that are collectively referred to as Primary Ciliary Dyskinesia (PCD). Classically, in patients with PCD, the cilia are rendered immotile and/or dysmotile by generalized structural abnormalities. It has been reported that PCD occurs with a prevalence of 1 in 16,000 births. There are no racial, geographic or sexual factors that predispose for PCD. PCD is inherited as an autosomal recessive trait that can result from defects in the gene coding for any one of the 200 proteins found in the ciliary axoneme. While the specific gene has not yet been identified, it is estimated that 1 in 70 person's are a carrier. Heterozygotes express no clinical signs or symptoms for PCD.
The pathogenesis of PCD first came to light in 1975 when Afzelius et al demonstrated a lack of inner and outer dynein arms in the tails of immotile sperm. Soon after that evidence was presented that demonstrated the same ciliary defects in two patients with chronic respiratory disease. Since then, numerous defects of the ciliary axoneme have been reported in association with PCD. Lack of dynein arms, however, remains the most commonly identified defect in these patients.
Clinically, patients with PCD demonstrate a number of generalized symptoms. The most common manifestations are bronchiectasis, chronic sinusitis, and male infertility. Rhinitis and chronic sinusitis are almost always seen, although immunoglobulin levels are rarely elevated. Additionally, roughly 30% of patients demonstrate nasal polyposis, as in this case. A history of chronic cough with purulent sputum production is also the norm, and results from the chronic infections associated with decreased mucous clearance. This is chronic bronchitis by definition, which is histologically characterized by bronchiectasis in older patients with PCD. Chronic otitis media and hearing loss are also seen, but usually in children and young adults.
Male infertility is also a rule. Sperm are normal in number, but are either immotile or dysmotile. An increase in female infertility has not been clearly documented and is still the subject of intense debate.
Kartagener's Syndrome is a variant of PCD that results from a combination of bronchiectasis, chronic sinusitis and situs inversus totalis. However, only 50% of patients with PCD have situs inversus. Accordingly, Kartagener's syndrome has a prevalence of approximately 1 in every 32,000 births.
In order to diagnose or confirm PCD, either a nasal biopsy or a sperm sample must be obtained. Ideally, samples should be obtained from two separate sites. Common practice calls for scraping a cytology brush along the middle and inferior turbinates. This should be repeated three times, with the specimens being placed in saline, formalin and 2.5% glutaraldehyde, respectively. The saline component should then be wet-mounted and viewed under a light microscope within thirty minutes of sampling. A properly mounted specimen will enable the pathologist to examine ciliary motion, or lack thereof. The formalin and glutaraldehyde fixed tissue can then be used for further histological analysis and electron microscopy, respectively.
Treatment of PCD is primarily targeted against upper and lower respiratory tract infections. Drug choice is usually based upon organisms cultured, although antimicrobials are often used to suppress colonization. Bronchodilators may also be necessary when addressing airway problems. Close monitoring of the lower respiratory tract can often delay the onset of bronchiectasis and atelectasis. Surgical intervention may be necessary for severe cases of nasal polyposis, atelectasis and chronic otitis media.
With current antibiotics and close monitoring, the life expectancy of patients with PCD is very close, if not within the normal range. Most patients lead productive lives and experience long periods of dormancy, although spontaneous remission is common.
Contributed by Jason C. Fowler, BS and Michael J. Becich, MD, PhD