PCD
Primary ciliary dyskinesia (PCD) is a rare autosomal recessive genetic disorder characterized by structural and functional defects in motile cilia, the microscopic hair-like projections that line the respiratory tract, fallopian tubes, and sperm flagella, impairing their ability to beat coordinately and clear mucus, pathogens, and debris from affected tissues.[1][2] Caused by biallelic mutations in over 50 genes involved in ciliary assembly, dynein arm formation, or microtubule organization, PCD manifests primarily through recurrent and chronic infections of the upper and lower respiratory tract, often beginning in infancy with neonatal respiratory distress in nearly all cases and persistent wet cough, nasal congestion, and otitis media.[3][4] Approximately 50% of affected individuals exhibit situs inversus totalis due to randomized left-right organ asymmetry during embryonic development, defining the subset known as Kartagener syndrome.[5] With an estimated prevalence of 1 in 10,000 to 20,000 births, PCD leads to progressive bronchiectasis, infertility in males and females, and, if undiagnosed, reduced life expectancy from suppurative lung disease, though early intervention can mitigate progression.[6][7] Diagnosis relies on a combination of clinical history, nasal nitric oxide measurement, high-speed video microscopy of ciliary beat pattern, electron microscopy for ultrastructural defects, and genetic testing, as symptoms overlap with common conditions like cystic fibrosis, often resulting in diagnostic delays of years.[8] There is no curative treatment, but multidisciplinary management emphasizing airway clearance techniques, prophylactic or culture-directed antibiotics, anti-inflammatory agents, and monitoring for complications such as hearing loss or hydrocephalus has improved outcomes, underscoring the importance of specialized centers for long-term care.[9][10]Biology and medicine
Primary ciliary dyskinesia
Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by defects in the structure or function of motile cilia, leading to impaired mucociliary clearance in the respiratory tract, fallopian tubes, and sperm flagella.[11][1] This results in chronic suppurative lung disease, recurrent upper respiratory infections, and, in approximately 40-50% of cases, situs inversus totalis as part of Kartagener syndrome.[11] PCD affects an estimated 1 in 10,000 to 20,000 individuals worldwide, with prevalence varying by population due to founder effects in certain ethnic groups.[1][12] The condition arises primarily from autosomal recessive inheritance, though rare autosomal dominant and X-linked forms exist, involving mutations in over 50 genes that encode proteins essential for ciliary assembly, motility, or beat coordination, such as dynein arms or axonemal components.[11] Common mutations include those in DNAH5 (accounting for about 22% of cases with outer dynein arm defects) and DNAH11 (11% of cases), often disrupting the 9+2 microtubule arrangement in cilia.[11][12] Genetic heterogeneity explains variable phenotypes, with 20-30% of clinically diagnosed cases lacking identifiable biallelic variants despite comprehensive testing.[11] Symptoms typically manifest early in life, with over 75% of full-term neonates experiencing respiratory distress requiring supplemental oxygen.[11] Key features include:- Persistent neonatal rhinosinusitis and wet cough from infancy.
- Recurrent otitis media with effusion, leading to conductive hearing loss in up to 70% of children.
- Chronic sinusitis and pneumonia, progressing to bronchiectasis in most untreated adults.
- Male infertility due to immotile spermatozoa; female subfertility from disrupted ovum transport.
- Organ laterality defects, including heterotaxy in 9-12% of cases, with risks of congenital heart disease or asplenia.[11][13]