Introduction
Demographics
Causes
Clinical features
Complications
Diagnosis
Differential diagnosis
Treatment
Prevention
Outcome
Primary ciliary dyskinesia (PCD) is a rare, congenital, genetic disorder of motile cilia that results in inefficient mucociliary clearance. The disorder is genetically and clinically heterogeneous, though common features include chronic pulmonary and otosinus disease and organ laterality defects.
Kartagener syndrome is a variant of PCD defined by the phenotypic triad of situs inversus, chronic sinusitis, and bronchiectasis.
Primary ciliary dyskinesia is typically inherited in an autosomal recessive manner, though some variants exhibit autosomal dominant or X-linked heritability. Sporadic cases have been rarely reported.
The estimated prevalence of PCD is 1 in 7500, and men and women are affected equally. Underdiagnosis and diagnostic delays are common, and the median age of diagnosis is 5.3 years despite symptoms presenting at birth or early infancy.
Prevalence is more common with consanguinity and in isolated ethnic groups where founder mutations are present.
Primary ciliary dyskinesia is caused by genetic defects of proteins involved in the function or ultrastructure of motile cilia, leading to ciliary immotility, dyskinesia, or sometimes aplasia (complete absence). There are more than 50 PCD-associated genes, and the clinical phenotype depends on the pathogenic variant present.
Cilia (singular: cilium) are tiny, hair-like projections found on the surface of cells. They can be broadly divided into two categories: motile and non-motile.
In PCD, dysfunction or absence of motile cilia results in secretory retention and obstruction, creating an environment prone to bacterial infection.
Motile cilia are also essential for oocyte transportation along the fallopian tubes, hence why PCD can cause female fertility issues. Sperm mobility may be impaired due to shared structural proteins between the flagellum and motile cilia, leading to male subfertility/infertility. Organ laterality defects (eg, situs inversus) can arise from involvement of nodal cilia during embryonic development.
Cutaneous manifestations in primary ciliary dyskinesia are rare, and the following have been described in case reports:
It remains unclear whether PCD is a causative factor in these manifestations.
Digital clubbing may be seen in association with bronchiectasis.
Symptoms typically appear shortly after birth, and 80% of newborn babies with PCD develop neonatal respiratory distress. From early infancy, patients frequently exhibit chronic otosinus and pulmonary symptoms, such as a year-round productive cough and nasal congestion.
Common features:
Uncommon features:
There is no single confirmatory investigation for primary ciliary dyskinesia due to its genetic and clinical heterogeneity.
Investigations should be performed based on clinical suspicion. PICADAR (primary ciliary dyskinesia rule) is a clinical score that predicts the likelihood of PCD and can guide further assessment.
Investigations:
Testing for other causes of bronchiectasis (eg, primary immunodeficiency, cystic fibrosis) is often done in parallel with PCD evaluation.
Currently, there are no curative or disease-modifying treatments available for primary ciliary dyskinesia. Management is supportive and focuses on the prevention and treatment of the sequelae of PCD, such as bronchiectasis and chronic rhinosinusitis.
Primary ciliary dyskinesia is a genetic condition with no known modifiable or environmental risk factors. Reproductive genetic counselling and pre-implantation genetic testing are available to families with a known pathogenic variant.
Primary ciliary dyskinesia is a lifelong genetic disorder. The prognosis varies and depends on the genotype, age at diagnosis, and clinical management. Many patients have stable respiratory function with a normal life expectancy, though a minority will experience severe respiratory disease requiring lung transplantation. Early diagnosis and multidisciplinary management may reduce morbidity, and long-term follow-up is essential.
