Kartagener Syndrome

Genetically transmitted polymalformative syndrome characterized by bronchiectasis, situs inversus, and chronic sinusitis.

Afzelius Syndrome; Dextrocardia-Bronchiectasis-Sinusitis; Immotile Cilia Syndrome, Kartagener type; Primary Ciliary Dyskinesia (PCD), Kartagener Type; Siewert Syndrome.

Genetic disorder first described by Siewert in 1904, but identified as a syndrome by the Swiss internist Manes Kartagener (1897-1975) in 1933.

1:32 000 live births. Primary ciliary dyskinesia (PCD), of which Kartagener's is a subtype, has an incidence of 1:16,000 live births. Only 20 to 25% of patients with situs inversus also have bronchiectasis and sinusitis.

Autosomal recessive trait. The axoneme of cilia contains 200 different proteins, and defects in genes coding for any one of these products could conceivably be responsible for PCD and thus Kartagener syndrome. Classically, Kartagener syndrome is caused by mutations in the gene encoding axonemal dynein intermediate chain (DNAI1), which maps to 9p21-p13. Other linkage studies have mapped the phenotype to 19q and 5p in Arabic families. Another mutation causing Kartagener syndrome has been mapped to the DNAH5 gene (5p15-p14).

Kartagener syndrome is essentially a subtype of an inherited disorder called primary ciliary dyskinesia (PCD), a heterogeneous disease characterized by functionally abnormal cilia that are “dysmotile” or, rarely, absent. Defects of all of the axonemal structures, alone or in combination, have been identified in association with PCD. Overly long, overly short, and normally appearing but randomly oriented cilia have been associated with PCD and Kartagener syndrome. Finally, normal ciliary ultrastructure has been described in patients with the clinical picture of Kartagener syndrome. Lack of dynein arms, which are structures that form temporary cross-bridges between adjacent ciliary filaments and are believed to be responsible for generating movement in cilia and sperm tails, remains the most common defect identified (type 1) and the one classically associated with Kartagener syndrome. Cilia of the respiratory tract and sperms are dysmotile or nonfunctional. It has also been postulated that normal visceral asymmetry is determined by movement of cilia in certain embryonic epithelial tissues; failure of embryonic cilia to function normally results in situs inversus.

The most important historical fact is the onset of upper and lower respiratory tract symptoms shortly after birth in the presence of situs inversus. Family history of PCD or Kartagener syndrome is very helpful, but the diagnosis may require examination of ciliary ultrastructure. To confirm the diagnosis, biopsy of respiratory mucosa or microscopic examination of sperms is required. Measurements of airway mucociliary clearance may be a valuable screening tool for excluding PCD because absent mucociliary clearance is a hallmark of the syndrome.

Kartagener syndrome is a clinical triad of chronic bronchorrhea with bronchiectasis, chronic sinusitis, and situs inversus. It can be regarded as a subgroup of primary ciliary dyskinesia (male sterility, bronchiectasis, sinusitis) because the clinical consequences are the same. Clinical signs appear soon after birth or early in childhood. Chronic rhinitis with nasal polyposis (approximately 30% of patients), agenesis of the frontal sinuses, and repeated otitis media are common. Conductive hearing loss may result. Anosmia is a frequent finding. Repeated episodes of atelectasis and pneumonia occur. Bronchiectasis subsequently develops during childhood and adolescence and affects primarily the dependent parts of the lung. In contrast, bronchiectasis from cystic fibrosis tends to affect primarily the upper lobes of the lungs. Reactive airways disease is a common feature. The situs inversus is often complete, but may only be partial (isolated dextrocardia or isolated transposition of abdominal viscera). Presumably, in an embryo that is homozygous for the mutation causing primary ciliary dyskinesia, there is no ciliary control of organ position. Therefore, approximately 50% of patients have situs solitus of the heart (levocardia), lungs, and abdominal organs, and the other 50% have partial or complete situs inversus, that is, Kartagener syndrome. A large number of patients with situs inversus are undiagnosed and asymptomatic. Additional cardiac malformations, such as atrial septal defect, right pulmonary artery hypoplasia, and transposition of the great vessels, usually occur in patients with isolated dextrocardia, levocardia with partial situs inversus (abdominal contents transposed), and dextrocardia with situs ambiguous (abdominal contents neither left nor right sided). Up to 90% of such patients have associated congenital heart disease, whereas only approximately 3% of patients with Kartagener syndrome have additional cardiac anomalies. Headaches, often of unclear etiology, are common. Communicating hydrocephalus, possibly as a result of impaired ependymal cilia function preventing CSF resorption, can occur. Asplenia is an infrequent finding, usually only seen in patients with situs ambiguus. Males are almost universally sterile because of absent sperm motility. Most women with Kartagener syndrome are fertile, despite the belief that ciliary action moves the ovum down the Fallopian tubes. Heterozygotes have normal ciliary function and no clinical features of PCD. Defective leukocyte migration has been reported in PCD, apparently secondary to cytoplasmic microtubule defects. This leukocyte problem has not been shown to have significant implications for the clinical course. With respect to respiratory manifestations, management is directed at early and aggressive treatment of sinusitis and pulmonary infections to prevent the impairment of respiratory function. Major congenital cardiac malformations may require corrective surgery.

Determine cardiac, thoracic, and abdominal anatomy prior to operation. Lung function by spirometry (forced expiratory volume at 1 second [FEV1], forced vital capacity [FVC], FEV1/FVC, total lung capacity, diffusing capacity of lung for carbon monoxide [DLCO]) may be normal or may show an obstructive pattern. A chest radiograph should be obtained to check for pneumonia and atelectasis. Arterial blood gases are useful if respiratory impairment is significant. Optimization of the respiratory function prior to surgery includes aggressive use of antibiotics to treat or prevent upper/lower respiratory tract infections, bronchodilators to reduce airway reactivity, and physiotherapy plus postural drainage to minimize secretions. Situs inversus, if present, is readily diagnosed by radiography. No treatment is required. If associated congenital heart disease is present, the usual considerations, such as current anatomy and functional state, current medications, endocarditis prophylaxis, and prevention of air embolism, apply. CT scan should be performed to rule out hydrocephalus and raised intracranial pressure, especially if the patient complains of headaches. Severe respiratory or cardiovascular compromise may dictate admission to an intensive care setting postoperatively or even preclude elective general anesthesia and surgery altogether.

Typical operations for patients with Kartagener syndrome include sinus surgery, pulmonary surgery, infertility investigations, or cardiac surgery. Local or regional anesthesia may be preferable to general anesthesia to minimize respiratory compromise. Nasal intubation may be relatively contraindicated if polyps with chronic sinusitis are present. Poor respiratory function and copious secretions secondary to bronchiectasis may make controlled ventilation and postoperative extubation difficult. Avoid increasing intracranial pressure or lowering cerebral perfusion pressure if raised intracranial pressure is a possibility. Transposed cardiac and respiratory anatomy must be kept in mind, for example, use of a right double-lumen tube instead of a left double-lumen tube and placement of an internal jugular line preferentially on the left instead of the right side.

No specific implications are directly associated with this medical entity.

Young Syndrome: Characterized by bronchiectasis, sinusitis, and obstructive azoospermia. Ciliary ultrastructure and function are normal in Young syndrome, as well as in cystic fibrosis, hypogammaglobulinemia, and allergic diathesis.

Primary Ciliary Dyskinesia: Characterized by immotility of the ciliary function in the respiratory system. Clinically, it is associated with chronic rhinitis, sinusitis, bronchitis, severely decreased mucociliary clearance of the lungs, and nasal polyps. However, there is no situs inversus in this condition.

α1-Antitrypsin Deficiency (AATD): Relatively common inherited disorder and primarily presents with early-onset panacinar lung emphysema and in a minority of the patients also with liver cirrhosis.

Mucoviscidosis: Congenital multiorgan disease affecting mainly the lungs, liver, and pancreas. Frequent lung infections, hemoptysis, intolerance to exercise, presence of finger clubbing suggesting pulmonary hypertension.