Primary ciliary dyskinesia
Primary ciliary dyskinesia, also known as immotile cilia syndrome, is the result of a congenital defect in the ultrastructure of cilia that renders them incapable of normal movement. It is associated with a number of anatomic and functional abnormalities.
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Epidemiology
Primary ciliary dyskinesia is caused by a heterogeneous group of genetic abnormalities which are inherited in an autosomal recessive pattern. The incidence variably estimated at 1:12,000-60,000 4,5.
Clinical presentation
As cilia are found in a number of locations both during the embryological period and extra-uterine life it is not surprising that a number of systems are involved. Most apparent is the involvement of the respiratory tract cilia and sperm. The clinical picture includes:
-
chronic sinusitis and chronic otitis media:
- earliest clinical manifestation, as early as 6 months of age 6
- diagnosis is nonetheless often not suspected especially in the absence of situs inversus
- conductive hearing loss is common and may result in language delay
- bronchiectasis: main cause of morbidity
- impaired fertility
- sterility in males
- increased rate of ectopic pregnancy/subfertility in females 5
Additionally, normal ciliary function is believed to be responsible for normal lateralization of the asymmetric chest and abdominal organs. In patients with primary ciliary dyskinesia, there is a random orientation, with 50% of patients demonstrating situs inversus 4.
Diagnosis is confirmed by:
- beat analysis of cilia demonstrating abnormal, reduced, or absent ciliary motion 5
- electron microscopic ultrastructural analysis of respiratory cilia demonstrating absence of, or abnormal dynein arms 4,5.
Two other tests are sometimes employed:
- saccharin test: time taken for sweet taste to be appreciated in the mouth, when a saccharin pellet is placed on the inferior turbinate, normal is less than 30 minutes 5
- nasal nitric oxide (nNO) measurement: typically very low (<250 ppb) in patients with PCD, CF, and severe rhinosinusitis 5
Pathology
A number of ciliary structural abnormalities are recognized, including 3,6:
- complete or partial absence of dynein arms: inner arms, outer arms or both
- radial spoke defect
- microtubular transposition
Irrespective of the specific defect, the result is abnormal ciliary movement, which manifest in a variety of epithelial surfaces (respiratory epithelium including that covering the middle ear, paranasal sinuses and pharynx), sperm tail movement and fallopian tube mucosa. The term 'immotile' may be a misnomer as some movement may be present, although it lacks coordination and strength 3.
Associations
A number of both syndromic and non-syndromic associations are recognized.
Syndromic
Various combinations of the above clinical features have been described as syndromes 2:
Non-syndromic
In addition, there may be an association with a number of other conditions, including:
- pectus excavatum 4
- hydrocephalus: thought due to abnormal ependymal cilia 5,7
- complex congenital heart disease 5
- biliary atresia 5
Radiographic features
Plain radiograph
Chest radiographic abnormalities are dominated by bronchial wall thickening, bronchiectasis and hyperinflation. In some instances, cystic bronchiectasis with air-fluid levels may be visible 6.
CT
HRCT chest
The most striking pulmonary abnormality is that of bronchial wall thickening and bronchiectasis, present in most patients. The distribution is either central or diffuse and has a predilection for the lower and middle lobes 4.
CT sinuses
Evidence of chronic sinusitis is prominent and may be seen as early as 6 months of age. The middle ears are chronically opacified, and polyps are seen in approximately 20% of cases.
Treatment and prognosis
The natural progression of primary ciliary dyskinesia is relatively slow compared to cystic fibrosis for example, but nonetheless, up to 25% of patients eventually develop respiratory failure 4.
Treatment largely consists of physiotherapy, early treatment of chest infection and immunisation against influenza virus 6.
As is the case with cystic fibrosis there appears to be higher than expected infection rate with P. aeruginosa 4.
Complications
Relate predominantly to bronchiectasis and diffuse lung disease, and include:
- chronic pulmonary infection
- hemoptysis
Differential diagnosis
Consider other causes of bronchiectasis, including:
- cystic fibrosis (see below)
- Williams-Campbell syndrome
- allergic bronchopulmonary aspergillosis (ABPA)
- congenital tracheobronchomegaly (also known as Mounier Kuhn syndrome)
Cystic fibrosis and primary ciliary dyskinesia share a number of similarities including 8:
- both are hereditary with autosomal recessive inheritance
- both have sinus and lung disease
- both have infertility in males
Fortunately, a number of differences usually enable a clinical distinction to be made relatively easily 8:
- immotile cilia
- basically normal mucus, cilia cannot move normally
- normal ductus deferens, sperm cannot swim normally
- radiologic findings are much milder
- cystic fibrosis
- abnormal mucus, cilia cannot clear it
- normal sperm, ductus deferens is obliterated
- radiologic findings are more severe
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