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.

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 .

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:

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 .

Diagnosis is confirmed by:

  • beat analysis of cilia demonstrating abnormal, reduced, or absent ciliary motion
  • electron microscopic ultrastructural analysis of respiratory cilia demonstrating the absence of, or abnormal dynein arms . 

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
  • nasal nitric oxide (nNO) measurement: typically very low (<250 ppb) in patients with PCD, CF, and severe rhinosinusitis

Pathology

A number of ciliary structural abnormalities are recognized, including :

  • 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 .

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 :

Non-syndromic

In addition, there may be an association with a number of other conditions, including:

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 .

CT

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 .

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 .

Treatment largely consists of physiotherapy, early treatment of chest infection and immunisation against influenza virus .

As is the case with cystic fibrosis there appears to be higher than expected infection rate with P. aeruginosa .

Complications 

Relate predominantly to bronchiectasis and diffuse lung disease, and include:

Differential diagnosis

Consider other causes of bronchiectasis, including:

Cystic fibrosis and primary ciliary dyskinesia share a number of similarities including :

  • 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 :

  • 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