Primary ciliary dyskinesia

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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 ^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/sub-fertility 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 the 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:

• Kartagener syndrome

• Young syndrome

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

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.

Cylindrical bronchiectasis is most common, and a diffuse bronchiolitis may be present ⁹.

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