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 ^4-5.

Associations

A number of both syndromic and non-syndromic associations are recognised. 

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

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 are 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 ⁵/ subfertility in females

Additionally, normal ciliary function is believed to be responsible for normal lateralisation 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 sweat 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 recognised, 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 the middle ear, paranasal sinuses and 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 co-ordination and strength ³.

Radiographic features

Plain film

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
• haemoptysis

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 vas deferens, sperm cannot swim normally
  • radiologic findings are much milder
• cystic fibrosis
  • abnormal mucus, cilia cannot clear it
  • normal sperm, vas deferens is obliterated
  • radiologic findings are more severe