Frequently Asked Questions

Primary ciliary dyskinesia is an unusual cause of chronic wheezing and cough in children. Occurring in approximately 1 in 12,000 to 20,000 births, it is an inherited condition that results from genetic abnormalities of the cilia. Ciliary dysfunction causes impaired clearance of inhaled particles, including bacteria, in the lung, paranasal sinuses, and middle ear. The abnormal mucociliary clearance of airway secretions causes a chronic bronchitis, and wheezing is a common clinical manifestation due to the mucus obstruction. In addition, repeated or persistent severe upper respiratory tract infections, usually in the form of chronic sinusitis or recurrent otitis media, are typical and occur in virtually every patient with "classic" forms of the disease. Half of the patients have situs inversus totalis (see below), and men are usually infertile.

Primary ciliary dyskinesia and immotile cilia syndrome are different names for the same disease. The latter has fallen out of favor because cilia in this condition do actually move, just not effectively or in a coordinated manner.

Kartagener syndrome is primary ciliary dyskinesia associated with situs inversus totalis, a medical term for the reversed, mirror-image orientation of the inner organs. Although Kartagener initially described several patients who presented with situs inversus totalis, chronic sinusitis and bronchiectasis, also known as the Kartagener triad, situs inversus is present in only half of the cases of this syndrome. In fact, its occurrence is random and not genetically predetermined, even within affected families.

The human lung is exposed daily to inhaled pathogens, allergens, and irritants, and innate host defenses are crucial to prevent pulmonary injury and infection. Complex, local defenses have evolved to protect the airways, including the mucociliary escalator, which mechanically eliminates bacteria and particulates that deposit at the respiratory epithelium.

Cilia completely line the nasopharynx, middle ear, paranasal sinuses, and larger airways. Each ciliated cell has hundreds of cilia that are oriented and beat in the same direction. A normal cilium is a complex, specialized structure, composed of roughly 250 proteins. It contains an array of longitudinal axonemal microtubules, consisting of 9 doublets arranged in an outer circle around a central pair [see Figure]. Radial spokes radiate from the central pair to microtubule A and an incomplete tubule B. The principal protein of the microtubules is a - and b -tubulin. The microtubules are anchored by a basal body in the apical cytoplasm of the cell. Dynein, an ATPase and "motor" of the cilium, is attached to the microtubules and appears as distinct inner and outer dynein arms, and provides energy for microtubule sliding. The shortening or absence of dynein arms (inner, outer, or both) is the most common form of the syndrome, occurring in ninety percent of cases with ultrastructural defects, but other structural abnormalities (like absent radial spokes) can produce decreased or absent ciliary movement.

Although there are similarities in their clinical presentation, primary ciliary dyskinesia and cystic fibrosis are different diseases caused by different genetic defects.

Many newborn babies with primary ciliary dyskinesia have respiratory distress requiring prolonged supplemental oxygen therapy and in some cases mechanical ventilator support.

Male sterility due to the impaired movement of spermatozoa also occurs, and infertility can be the presenting feature of the disease in adult men. Cardiac anomalies (besides situs inversus totalis) and hydrocephalus have also been described in affected patients.

Men are frequently infertile because their spermatozoa are poorly motile. Although there are concerns about reduced fertility and an increased risk of ectopic (tubal) pregnancies, women with primary ciliary dyskinesia can have children.

The diagnosis of primary ciliary dyskinesia requires a high index of suspicion, and must be differentiated from acquired forms caused by different environmental and infectious agents, which produces a number of secondary changes that cause transient ciliary dysfunction. It requires the presence of characteristic clinical features and ultrastructural defects of cilia; however, not all forms of primary ciliary dyskinesia have associated structural abnormalities.

Qualitative and functional assays for ciliary function, including crude measures of mucociliary clearance like the saccharin test, have limited usefulness since they are not well-standardized and do not distinguish between primary and secondary causes of ciliary dyskinesia. Findings on chest radiographs (x-rays) are often non-specific, but frequently show areas of pulmonary infiltrates or atelectasis. Bronchiectasis is usually a late, irreversible consequence. Ultimately, because primary ciliary dyskinesia is an inherited disease, genetic testing for many forms of the disease will be developed and used. But that is the future, and one of the many goals of the consortium.

While some patients with primary ciliary dyskinesia may have normal lifespans, some patients can have considerable morbidity related to the lung disease, which can interfere with quality of life or even require lung transplantation.

Bronchiectasis is defined as the abnormal dilatation of the affected segmental and sub segmental bronchi and is associated with persistent infections of the airways. Bronchiectasis is a pathophysiologic description, not a discrete disease, and is the consequence of many chronic airway diseases, like primary ciliary dyskinesia and cystic fibrosis.

Although it cannot be avoided, there is considerable evidence in other diseases that the progression of bronchiectasis can be slowed by regular airway clearance. No general consensus exists about the use of prophylactic antibiotics to prevent infection or reduce bacterial burden in the lungs, but it is clear that antibiotic therapy is a key component to treatment of pulmonary exacerbations.

Cultures of lower respiratory tract secretions from primary ciliary dyskinesia patients frequently yield upper respiratory flora, including Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Pseudomonas aeruginosa.

The persistent middle ear effusions seen in primary ciliary dyskinesia cannot be prevented, but early and aggressive use of antibiotic therapy can treat acute otitis media. The use of tympanostomy (or myringotomy) tubes to treat middle ear disease is considered by some otolaryngologists to be a "double-edged sword." Their placement can potentially improve hearing, but chronic drainage (otorrhea) is a common complication of tympanostomy tubes in primary ciliary dyskinesia patients.

In cases of severe, advanced lung disease, transplantation may be the only treatment option available.