What is Kartagener syndrome?

What is Kartagener Syndrome?

Kartagener syndrome is a rare autosomal recessive genetic disorder that represents a specific subset of primary ciliary dyskinesia (PCD), characterized by the classic triad of situs inversus totalis, bronchiectasis, and chronic sinusitis or nasal polyposis. 1, 2

Underlying Pathophysiology

The fundamental defect in Kartagener syndrome involves abnormal ciliary structure and function, leading to impaired mucociliary clearance throughout the respiratory tract. 1, 2

• Genetic basis: More than 35 causal genes have been identified for PCD, with the majority following an autosomal recessive inheritance pattern, though autosomal-dominant and X-linked cases have been reported. 1, 2
• Ciliary defects: Two-thirds of ultrastructural defects occur in the outer dynein arm of the ciliary axoneme, resulting in ciliary immotility or dyskinesia (abnormal movement). 1, 2
• Incidence: Kartagener syndrome occurs in approximately 1 in 20,000 to 1 in 60,000 live births. 1, 2

Clinical Manifestations

The Classic Triad

Situs inversus totalis occurs in approximately 50-55% of all PCD patients, and when present with the other features, defines Kartagener syndrome. 1, 2

Bronchiectasis develops from chronic inflammatory injury due to defective epithelial ciliary clearance of secretions from the lower airways, and is present in virtually all PCD patients. 1, 3

Chronic rhinosinusitis occurs in 100% of PCD patients, often accompanied by nasal polyposis and agenesis of the frontal sinuses. 1, 2, 3

Respiratory Manifestations

• Neonatal respiratory distress is often the first clinical presentation in newborns. 1
• Recurrent upper respiratory infections including chronic sinusitis, otitis media, and otosalpingitis occur throughout life. 1
• Chronic productive cough results from impaired mucociliary clearance and recurrent lower respiratory infections. 1, 4
• Difficult-to-control asthma with mild to moderate airway obstruction that may respond to bronchodilators. 1, 5

Fertility Issues

Male infertility is nearly universal in Kartagener syndrome due to immotile sperm caused by the same ciliary defects affecting respiratory cilia. 2, 3

• Female fertility may also be affected due to impaired fallopian tube ciliary function. 6

Associated Conditions

Beyond the classic triad, several additional conditions may occur:

• Hydrocephalus from impaired cerebrospinal fluid circulation. 5, 2
• Congenital heart disease occurs in approximately 5% of cases. 2, 7
• Scoliosis affects 5-10% of patients. 2
• Humoral immunodeficiency is present in 6.5% of cases. 2
• Polycystic kidney disease, biliary atresia, and retinitis pigmentosa are rare associations. 5, 2

Diagnostic Approach

Clinical Recognition

When the classic triad of chronic sinusitis, bronchiectasis, and situs inversus is present, diagnosis should not be delayed while waiting for specialized testing. 3

Screening Tests

Nasal nitric oxide (nNO) measurement serves as an excellent initial screening test:

• A cutoff of <30 nL/min has 91% sensitivity and 96% specificity for PCD. 5, 2, 3

Confirmatory Testing

High-speed video microscopy analysis (HSVMA) of ciliary beat frequency and pattern from nasal brushings:

• Demonstrates 100% sensitivity and 93% specificity for PCD. 5, 2, 3

Transmission electron microscopy (TEM) of ciliary ultrastructure:

• Should be performed when HSVMA is abnormal, with 79% sensitivity and 100% specificity. 5, 2, 3

Genetic testing can identify specific mutations in the >35 known PCD-causing genes. 1, 2

Imaging Studies

• Chest CT scan to evaluate the extent and distribution of bronchiectasis. 5, 3
• Sinus CT scan to document chronic sinusitis and frontal sinus agenesis. 5, 3
• Chest radiograph to identify dextrocardia and situs inversus. 1

Critical Pitfalls to Avoid

Do not assume all PCD patients have situs inversus — only 50-55% present with this finding, and its absence does not exclude PCD. 2, 3

Do not delay PCD testing for years while treating individual infections when the clinical presentation is characteristic, as this causes chronic respiratory problems with reduced quality of life. 3, 4

Do not rely solely on glucose testing for CSF rhinorrhea in patients with refractory clear rhinorrhea, as β-2-transferrin protein is more sensitive and specific. 1

Management Principles

Long-term Respiratory Care

Daily chest physiotherapy and airway clearance techniques form the cornerstone of management, addressing the fundamental defect in mucociliary clearance. 3

Bronchodilators should be used when spirometry demonstrates mild-to-moderate obstruction with positive bronchodilator response. 1, 5, 3

Prophylactic antibiotics may be considered for recurrent infections. 4

Surveillance

• Regular spirometry (every 6-12 months) to detect progressive airway obstruction. 5, 3
• Periodic chest CT (every 2-3 years) to monitor bronchiectasis progression. 3
• Vaccination with pneumococcal and influenza vaccines to reduce infection risk. 3

Counseling

Genetic counseling should be offered given the autosomal recessive inheritance pattern, particularly with family history or parental consanguinity. 5, 2, 3

Fertility counseling is essential, especially for males who face near-universal infertility. 5, 2, 3