Overview
This lecture covers Kartagener syndrome (primary ciliary dyskinesia), focusing on its genetics, clinical features, and how to differentiate it from similar diseases like cystic fibrosis.
Genetic Basis of Kartagener Syndrome
- Kartagener syndrome is caused by mutations in DNAI1 or DNAH5 genes.
- These genes code for dynein arm proteins (light chain 1 and heavy chain 5) in cilia.
- Defective dynein arms impair microtubule sliding, leading to dysfunctional ciliary and flagellar motion.
Clinical Features
- Impaired ciliary motion affects all organs where cilia are important.
- Recurrent pulmonary infections occur due to poor mucociliary clearance in the respiratory tract.
- Infertility can occur in both males (immotile sperm) and females (impaired fimbriae movement, risk of ectopic pregnancy).
- Situs inversus (reversed thoracoabdominal organ orientation) is seen in about 50% of patients.
- Secondary features may include conductive hearing loss (from chronic otitis media) and nasal polyps (from recurrent infections).
Differential Diagnosis: Cystic Fibrosis vs. Kartagener Syndrome
- Both conditions can cause recurrent pulmonary infections, male infertility, and nasal polyps.
- Cystic fibrosis infertility is due to congenital absence of the vas deferens.
- Cystic fibrosis may present with pancreatic insufficiency (fat-soluble vitamin deficiency: A, D, E, K), positive sweat test, clubbing, and meconium ileus.
- Genetic cause for cystic fibrosis is CFTR gene mutation on chromosome 7.
- Presence of situs inversus points towards Kartagener syndrome.
Key Terms & Definitions
- Kartagener Syndrome (Primary Ciliary Dyskinesia) — Genetic disorder causing defective ciliary motion.
- Dynein Arm — Motor protein complex necessary for ciliary and flagellar motility.
- Mucociliary Clearance — Cilia-driven removal of mucus from the respiratory tract.
- Situs Inversus — Reversal of internal thoracoabdominal organ orientation.
- CFTR gene — Gene mutated in cystic fibrosis.
Action Items / Next Steps
- Review symptoms and diagnostic clues for Kartagener syndrome vs. cystic fibrosis.
- Memorize key genetic and clinical distinctions for exam preparation.