Primary Ciliary Dyskinesia

Goal 1.

Describe the clinical characteristics of primary ciliary dyskinesia.

Goal 2.

Review the genetic causes of primary ciliary dyskinesia.

Goal 3.

Provide an evaluation strategy to identify the genetic cause of primary ciliary dyskinesia in a proband.

Goal 4.

Inform genetic counseling of family members of an individual with primary ciliary dyskinesia.

Goal 5.

Review management of primary ciliary dyskinesia.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with primary ciliary dyskinesia (PCD), the following evaluations are recommended:

• Pulmonary disease
  • Respiratory cultures (typically sputum cultures) to define infecting organisms and to direct antimicrobial therapy. Specific cultures for non-tuberculous mycobacteria should be included for older children and adults.
  • Chest radiographs and/or chest CT to define distribution and severity of airway disease and bronchiectasis
  • Pulmonary function tests (spirometry) to define severity of obstructive impairment
  • Pulse oximetry, with overnight saturation studies if borderline
• Nasal congestion and/or sinus symptoms. Sinus imaging (sinus x-rays or preferably sinus CT examination)
• Chronic/recurrent ear infections. Formal hearing evaluation (See Deafness and Hereditary Hearing Loss Overview for hearing evaluations available at different ages.)
• Other. Clinical genetics consultation

Treatment of Manifestations

To date, no specific therapies can correct ciliary dysfunction. The therapies described in this section are empiric and aimed at treating consequences of dysfunctional cilia and sperm flagella. Little evidence supports use of specific therapeutic modalities in PCD.

Pulmonary disease. Management of individuals with PCD should include aggressive measures to enhance clearance of mucus, prevent respiratory infections, and treat bacterial infections.

Approaches to enhance mucus clearance are similar to those used in the management of cystic fibrosis, including chest percussion and postural drainage, oscillatory vest, and breathing maneuvers to facilitate clearance of distal airways. Because cough is an effective clearance mechanism, patients should be encouraged to cough and engage in activities that promote deep breathing and cough (e.g., vigorous exercise).

Routine immunizations to protect against respiratory pathogens:

• Pertussis
• Haemophilus influenzae type b
• Pneumococcal vaccine
• Annual influenza virus vaccine

Prompt institution of antibiotic therapy for bacterial infections of the airways (bronchitis, sinusitis, and otitis media) is essential for preventing irreversible damage. Sputum culture results may be used to direct appropriate choice of antimicrobial therapy. In those individuals in whom symptoms recur within days to weeks after completing a course of antibiotics, extended use of a broad-spectrum antibiotic or even prophylactic antibiotic coverage may be considered. (Consideration of chronic antibiotic therapy must include assessing the risk of selecting for multiresistant organisms.)

For individuals with localized bronchiectasis, lobectomy has been performed in an attempt to decrease infection of the remaining lung. This approach, however, is controversial; consultants with expertise in PCD should be involved in the decision-making process.

Lung transplantation has been performed in persons with end-stage lung disease.

Nasal congestion and sinus infections. In some persons with extensive sinus disease, sinus surgery can facilitate drainage and relieve symptoms.

Chronic/recurrent ear infection. For chronic otitis media unresponsive to antibiotic therapy, PE tube placement may be helpful; however, some individuals with PCD have persistent mucoid discharge following PE tube placement [Hadfield et al 1997].

Speech therapy and hearing aids may be necessary for children with hearing loss and delayed speech.

Male infertility. A couple in which the male has PCD-related infertility has the option of in vitro fertilization using ICSI (intracytoplasmic sperm injection). In this procedure, spermatozoa retrieved from ejaculate (in males with oligozoospermia) or extracted from testicular biopsies (in males with obstructive azoospermia) are injected into a harvested egg by in vitro fertilization [Sha et al 2014].

Another option is artificial insemination by donor sperm.

Situs abnormalities. Typically, situs abnormalities do not require intervention unless physiologic dysfunction (e.g., congenital heart disease) requiring surgical intervention is present.

Prevention of Secondary Complications

Appropriate preventive measures:

• Routine immunizations (including influenza vaccine and pneumococcal vaccine) to prevent respiratory infections
• Education about infection control including attention to hand washing, avoidance of sick contacts, proper cleaning/disinfecting of respiratory devices, and early use of antibiotics for respiratory illnesses (directed by prior respiratory cultures)

Surveillance

Follow up by a pulmonologist to monitor lung function and pathogens in sputum cultures as well as to assess pulmonary disease extent/progression is indicated.

For young children with chronic otitis media, routine hearing evaluation is essential, and should be continued until the teenage years, by which time hearing is usually normal [Majithia et al 2005]. Typically, the ear disease improves in later childhood and hearing screening is not necessary.

Agents/Circumstances to Avoid

Cough suppressants should not be used because cough is critical for clearing secretions.

Exposure to respiratory pathogens, tobacco smoke, and other pollutants and irritants that may damage airway mucosa and stimulate mucus secretion should be avoided.

Evaluation of Relatives at Risk

It is appropriate to evaluate the older and younger sibs of a proband in order to identify as early as possible those who would benefit from initiation of treatment and preventive measures.

• If the pathogenic variants in the family are known, molecular genetic testing can be used to clarify the genetic status of at-risk sibs.
• If the pathogenic variants in the family are not known, a rigorous clinical history and physical examination accompanied by chest imaging and nasal nitric oxide measurements can be used to clarify the disease status of at-risk sibs.

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Pregnancy Management

For a female with PCD, any pulmonary infections and pulmonary functional status should be rigorously evaluated by an expert in PCD (or cystic fibrosis) to define the risk associated with child bearing.