Kartagener syndrome is an autosomal recessive inherited disease. Primary defects in the structure and function of sensory and motile cilia result in multiple ciliopathies
Current nomenclature classifies all congenital ciliary disorders as primary ciliary dyskinesias in order to differentiate them from acquired types. The cilia line upper airways, including the nasal mucosa, paranasal sinuses, middle ear, eustachian tube, and pharynx. The lower respiratory tract contains ciliated epithelium from the trachea to the respiratory bronchioles. Each ciliated cell gives rise to approximately 200 cilia that vary in length from 5-6 μm and decrease in size as the airway becomes smaller. These cilia do not function in Kartagener disease and exhibit an uncoordinated and inefficient movement pattern
The incidence of the genetic disorder is estimated to be between 1 in 15,000 and 1 in 30,000 without differences between men and women
The cause is genetic, with an autosomal recessive inheritance pattern. Genome analysis has found it is genetically heterogenous. Genes DNAH5 and DNA11 on bands 5p15.1 and 9p13,3 respectively, are known to cause primary ciliary dyskinesia. Both genes encode for dynein. Ciliary ultrastructure is examined qualitatively for abnormalities in dynein arms (inner and outer), radial spokes, central sheaths, nexin links, and ciliary transposition and orientation. The most common ultrastructural defect is an absence or decrease in the number of inner or outer dynein arms. A radial spoke deficiency commonly appears with a dynein arm deficiency
Kartagener syndrome is characterized by this clinical triad:
- Situs inversus (transposition of the viscera): The dysfunction of the cilia manifests during the embryologic phase of development because normal-functioning cilia determine the position of the internal organs during early embryological development. 50% individuals with Kartagener's syndrome have a chance of developing situs inversus
- Abnormal frontal sinuses (producing sinusitis and bronchiectasis
- Primary ciliary dyskinesia (PCD) : cilia 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
Other clinic manifestations:
Nose: mucoid rhinorrhea from early in childhood. Nasal polyps are recognized in 30% of affected individuals.
Sinuses: sinus pressure headaches in the maxillary and periorbital region.
Ears: recurrent otitis media and conductive deafness
Eye: retinitis pigmentosa and corneal abnormalities
Lower respiratory tract: chronic bronchitis and recurrent pneumonia, obstructive lung which probably results from elevated levels of local inflammatory mediators in a chronically irritated airway.
Males demonstrate infertility secondary to immotile spermatozoa, dextrocardia and asplenia
Kartagener's syndrome and infertility:observation, diagnosis and treatment
Primary flagellar abnormality is associated with an increased rate of spermatozoa aneuploidy
Function and structure of cilia in the Fallopian tube of an infertile woman with Kartagener syndrome
Sinus radiographs typically demonstrate mucosal thickening, opacified sinus cavities, and hypoplastic frontal sinuses.
Chest radiographs may illustrate bronchial wall thickening as an early manifestation of chronic infection, hyperinflation, atelectasis, bronchiectasis, and situs inversus (in 50% of patients with primary ciliary dyskinesia)
Bronchiectasis occurs in the lower lobes in patients with Kartagener syndrome and immunoglobulin deficiency, while bronchiectasis predominantly occurs in the upper lobes of patients with cystic fibrosis.
Screening tests include the saccharin test and the measurement of nasal and exhaled nitric . The first one is placed in the nose, and the speed of transport into the nasopharynx is measured to calculate mucociliary clearance
Nitric oxide: In patients with primary ciliary dyskinesia, exhaled and nasal nitric oxide is low. There are two possible explanations for the low nasal NO values
1) the production of NO is absent
2) the diffusion of NO into the airway lumen is reduced in some way due to impaired mucociliary clearance
If the low NO levels are due to a reduced production, this could be explained by a deficient NO synthesis in the superficial structures of the nasal airways. Ciliated epithelial cells normally contain NO synthase and NO may be involved in the regulation of ciliary movements, indicating that the ciliary dysfunction and the impaired NO synthesis seen in Kartagener's syndrome could be interrelated. It remains to be determined whether stimulation of NO production may be useful in the treatment of these patients. The NO synthase in the nasal airways is likely to be of a constitutive isoform rather than an inducible one, since local treatment with corticosteroids, that are known to inhibit the inducible enzyme, did not affect NO levels in exhaled air. However, the presence of an inducible NO synthase cannot be excluded, since this isoform has been demonstrated in normal tracheobronchial epithelium
3) bacteria are involved in the synthesis of NO in normal nasal mucosa. Some bacteria are known to produce NO from nitrite, and patients with Kartagener's syndrome are often treated
with antibiotics. Therefore, the low NO production could be explained by differences in the nasal bacterial composition
Nasal nitric oxide concentration in paranasal sinus inflammatory
Risks and complications
Complications include bronchiectasis, pneumonia, conductive deafness, and communicating hydrocephalus. An other kind of risk is the Broncholithiasis
It is an unusual entity defined by the presence of hilar calcifications or calcified peribronchial lymphnodes that erode the bronchial wall and can enter the bronchial lumen, giving rise to clinical and radiologic abnormalities. Infection by Mycobacterium tuberculosis is currently the main cause of broncholithiasis, followed by infection by Histoplasma capsulatum. One sign of broncholithiasis is lithoptysis, which consists of expectoration of one or more broncholiths, an event that can resolve the clinical picture in some cases
Treatment and medical care
Antibiotics are used to treat acute or chronic infection or for prophylaxis against infection like Haemophilus influenza and Staphylococcus aureus which are the most common.Trimethoprim, sulfamethoxazole, Amoxicillin clavulanate and Guaifenesin .
Obstructive lung disease/bronchiectasis should be treated with inhaled bronchodilators, mucolytics and chest physiotherapy
Influenza and pneumococcal vaccination should be encouraged
Tympanostomy tubes are required to reduce conductive hearing loss and recurrent infections.
When sinus disease is refractory to medical management, functional endoscopic sinus surgery leads to transient improvement in upper and lower respiratory tract symptoms