Syndromes Associated with Situs Inversus
The primary syndrome associated with situs inversus is Kartagener syndrome, which occurs in approximately 50% of patients with primary ciliary dyskinesia (PCD) and consists of the classic triad of situs inversus totalis, bronchiectasis, and chronic sinusitis. 1
Primary Ciliary Dyskinesia and Kartagener Syndrome
Primary ciliary dyskinesia is the main genetic disorder linked to situs inversus, representing an autosomal recessive condition caused by defective ciliary structure and function. 1
Key Clinical Features of PCD with Situs Inversus:
Situs inversus occurs in approximately 50-55% of all PCD patients, making it a defining feature when present but not required for PCD diagnosis. 1
The complete Kartagener syndrome triad includes: situs inversus totalis, bronchiectasis, and either chronic sinusitis or nasal polyps. 1, 2
Chronic rhinosinusitis occurs in virtually 100% of PCD patients, with recurrent otitis media in 95%, and neonatal respiratory distress in 73%. 1
Male infertility is nearly universal in PCD due to immotile sperm from the same ciliary defects. 1
Diagnostic Approach When Situs Inversus is Present:
When situs inversus is identified with any respiratory or nasal symptoms, PCD testing should be pursued immediately. 1
Nasal nitric oxide (nNO) measurement serves as an excellent screening test, with levels <30 nL/min having 91% sensitivity and 96% specificity for PCD. 1
High-speed video microscopy analysis (HSVMA) of ciliary beat frequency and pattern from nasal brushings has 100% sensitivity and 93% specificity. 1
Transmission electron microscopy (TEM) of ciliary ultrastructure demonstrates 79% sensitivity and 100% specificity, with two-thirds of defects occurring in the outer dynein arm. 1
Associated Conditions Beyond the Classic Triad:
Additional PCD-associated conditions include: hydrocephalus, polycystic kidney disease, biliary atresia, scoliosis (5-10%), humoral immunodeficiency (6.5%), congenital heart disease (5%), and retinitis pigmentosa. 1
Heterotaxy syndromes with cardiac disease should prompt evaluation for respiratory, nasal, or ear problems suggestive of PCD. 1
Clinical Pitfalls and Important Caveats:
Not all patients with situs inversus have PCD—the condition must be distinguished from isolated situs inversus or other heterotaxy syndromes without ciliary dysfunction. 1
Conversely, approximately 45-50% of PCD patients have normal organ positioning (situs solitus), so absence of situs inversus does not exclude PCD. 1
The specificity of situs inversus for PCD is high at 93.9%, but sensitivity is only 50.8%, meaning it identifies only half of PCD cases. 1
Early diagnosis is critical—delayed recognition leads to irreversible bronchiectasis and progressive lung destruction that could be prevented with timely management. 3, 4, 5
In neonates presenting with unexplained respiratory distress requiring oxygen >24 hours, the combination of situs inversus, lobar collapse, or oxygen need >2 days has 87% sensitivity and 96% specificity for PCD. 1
Genetic Considerations:
More than 35 causal genes have been identified for PCD, with the five most common being DNAH5, DNAH11, DNAI1, CCDC39, and CCDC40. 1
Family history of PCD and parental consanguinity are strong risk factors given the autosomal recessive inheritance pattern. 1
The incidence is approximately 1 in 20,000 live births, though this may be underestimated due to underdiagnosis of cases without situs inversus. 1