Kartagener's Syndrome

Synonyms: Afzelius' syndrome, Kartagener's triad, Siewert's syndrome, Dextrocardia-bronchiectasis-sinusitis syndrome, primary ciliary dyskinesia

This is described as autosomal recessive inherited syndrome. Primary (genetic) defects in the structure and function of sensory and motile cilia result in multiple ciliopathies.

It consists of a triad of features:

• Situs inversus (transposition of the viscera)
• Abnormal frontal sinuses (producing sinusitis and bronchiectasis)
• Primary ciliary dyskinesia (PCD).¹

The defective cilia lining the respiratory tract are unable to clear the airways of secretions and pathogenic bacteria, resulting in mucus retention and chronic or recurrent respiratory tract infection - leading to damage to airways walls. Approximately half of patients with PCD have the full triad of Kartagener's syndrome.² There may also be a link with retinitis pigmentosa and hearing loss.^3,4

The incidence of the genetic disorder is estimated to be between 1 in 15,000 and 1 in 30,000.⁵

History

In children, wheezing with a chronic loose or productive cough, chronic or recurring upper and lower respiratory tract infections, sinusitis and otitis media. Male infertility, and decreased fertility in females may also occur.

Examination

Findings may include dextrocardia and situs inversus, asplenia, nasal polyps, rhinitis, corneal abnormalities, conductive deafness. Extremities may exhibit distal clubbing.

Conditions which may need to be considered include:

• Allergic rhinitis
• Adenoid hyperplasia
• Allergic bronchopulmonary aspergillosis
• Bronchial obstruction
• Chronic aspiration
• Congenital cartilage deficiency
• Cystic fibrosis
• Idiopathic nasal polyposis
• Inhalation of toxic substances
• Postinfectious bronchiectasis
• Pulmonary sequestration
• Samter triad (asthma, aspirin sensitivity, and nasal/ethmoidal polyposis)
• Severe atopy
• Tracheobronchomegaly
• Yellow nail syndrome

• Chest X-ray may show dextrocardia, lung over-inflation, bronchial wall thickening and peribronchial infiltrates. Right-sided heart disease with chronic respiratory tract symptoms is highly indicative and occurs in half of patients.
• CT for bronchiectasis and to demonstrate involvement of paranasal sinuses (poorly aerated mastoids ±absence of frontal sinuses).
• Transmission electron microscopy of cilia from airway biopsy (nasal mucosa or tracheal mucosa taken when the patient is not acutely ill). The specimen is examined for ciliary movement, beat frequency, coordination and amplitude.The most common ultrastructural defect is an absence or decrease in the number of inner or outer dynein arms. This investigation is helpful in differentiating primary from secondary ciliary dysfunction.
• Semen analysis in post-pubertal males may reveal abnormal sperm motility and ultrastructure.
• The saccharin test is only used occasionally due to pragmatic difficulties. Saccharin is placed in the nose, and the speed of transport to the nasopharynx is measured.
• Measurement of nasal nitrous oxide is a useful screening test, which has the advantage of being non-invasive.⁶

Efforts to standardise the clinical criteria for the diagnosis of Kartagener's Syndrome have centred on dextrocardia, a ciliary beat frequency of less than 10 Hz/s, and a mean cross-section dynein arm count of less than 2. If the patient does not have dextrocardia, the identification of primary ciliary dyskinesia becomes the mainstay of diagnosis. Genetic testing ultimately may become the principal means of establishing this diagnosis.⁷

Medical care

• Antibiotics, intravenous or oral, intermittent or continuous, are used to treat upper and lower airway infections. Long-term low-dose prophylactic antibiotics may be necessary in children.
• Obstructive lung disease/bronchiectasis should be treated with inhaled bronchodilators, mucolytics and chest physiotherapy.⁸ The evidence base is largely anecdotal, but there may also be a role for inhaled antibiotics, inhaled and oral corticosteroids, and recombinant DNAs.
• Influenza and pneumococcal vaccination should be encouraged.

Surgical care

• Tympanostomy tubes will reduce recurrent infections and conductive hearing loss. Repeated insertions may be required, and chronic suppurative otitis media can be annoying complication. Aural hygiene measures such as acetic acid irrigations, otomicroscopy, or topical or systemic antibiotic therapy may be required.
• Endoscopic sinus surgery and the formation of a nasal antral window underneath the inferior turbinate, may afford a transient improvement in upper and lower respiratory tract symptoms.
• Lobectomy is sometimes required for the associated bronchiectasis.⁹ Lung transplantation and heart-lung transplantation has occasionally been tried in severe cases, with some success.^10,11

Complications include bronchiectasis, pneumonia, conductive deafness, and communicating hydrocephalus.

Treatment with antibiotics, physiotherapy and appropriate surgical intervention have improved the prognosis in these patients, and in some cases lifespan may be normal.