Primary ciliary dyskinesia overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Hafsa Ghaffar, M.B.B.S[2]
Overview
Primary ciliary dyskinesiaPCD is an autosomal recessive disorder characterised by functional defects in the cilia resulting in an abnormal mucociliary clearance.Epithelial cells containing motile cilia are localised in the respiratory tree, oviduct, sperms, ventricles of the brain and embryonic node. Defects in the epithelial cells accounts for the majority of symptoms of PCD including sinusitis, otitis media and bronchiectasis. Situs inverses(in some patients) and rarely hydrocephalus. While the understanding of the cellular and molecular mechanisms responsible for these symptoms has progressed recently, genetic analysis has identified mutations in only two axonemal dynein genes that can account for abnormal cilia structure.Nasal nitric oxide Nno is the screening test that could be performed initially to diagnose PCD initially followed by electron microscopy to confirm the diagnosis. Treatment mainly focuses on treating underlying conditions that can exacerbate PCD such as antibiotics for rhino-sinusitis, bronchiectasis, and sinusitis.
Historical Perspective
In 1981, Rossman and coworkers came up with the term primary ciliary dyskinesia (PCD) because some patients with Kartagener syndrome had cilia that were not immotile but exhibited an uncoordinated and inefficient movement pattern.
Classification
There is no established system for the classification of primary ciliary dyskinesia.
Pathophysiology
In many people with primary ciliary dyskinesia, the cause of the disease is unknown, but the main factor contributing to the pathogenesis is mutations in the proteins forming the cilia which result in the formation of abnormal or immotile cilia. Clearly, cilia have many important functions within the body, defects in these cell structures cause a variety of signs and symptoms.
Causes
There are no established causes for Primary ciliary dyskinesia, PCD is related to defects in mucociliary clearance due to abnormal ciliary structure. Mutations in around 46 different genes throughout the genome have been found to be causative. Some of these include DNAH5, CCDC39, DNAI1, CCDC40, DNAH11, ZMYND10, CCDC103, CCDC151 and ARMC4.
Differentiating Primary ciliary dyskinesia from Other Diseases
Primary ciliary dyskinesia must be differentiated from other conditions that cause infertility, sinusitis, otitis media, and rhinitis.
Epidemiology and Demographics
Primary ciliary dyskinesia (PCD) is generally documented as aetiology of bronchiectasis not only in children or young adults but also in older patients. It is challenging to demonstrate the prevalence of PCD in diverse population with estimates varying between one in 4000 to one in 40,000. PCD is linked with the high levels of consanguinity. Clinical suspicion of PCD is high in these communities, chronic cough and nasal symptoms should rise concern for prompt diagnostic testing.
Risk Factors
There are no established risk factors for primary ciliary dyskinesia.
Screening
There is insufficient evidence to recommend routine screening for primary ciliary dyskinesia, however patients with persistent sinusitis, rhinitis, and no known aetiology should be screened by nasal nitric oxide test, low levels of nasal nitric oxide is diagnostic of primary ciliary dyskinesia and should prompt further testing with biopsy and ciliary beat pattern(CBP).
Natural History, Complications, and Prognosis
The long-term effects of primary ciliary dyskinesia (PCD) are dependent on respiratory symptoms. PCD is not considered to be life-threatening, but persistent lung and airway disease can lead to permanent damage. Recurrent ear infections can lead to hearing loss, which is sometimes permanent, prompt diagnosis and early treatment improve long-term outcomes.
Diagnosis
A high level of suspicion is required to warrant early diagnosis and initiation of appropriate management before irreversible lung damage ensues. Diagnostic investigations are complex, requiring expensive arrangements and an experienced team of clinicians and scientists. People with persistent respiratory symptoms such as rhinitis, rhino-sinusitis, infertility, recurrent otitis media should seek medical care and undergo further testing. Nasal nitric oxide levels are low in PCD and should be performed as a screening test. Transmission electron microscopy to assess the ultrastructure of cilia is another important investigation that can confirm the diagnosis.
Diagnostic Study of Choice
There is no single diagnostic test for primary ciliary dyskinesia. A combination of the following techniques could contribute to the diagnosis of Primary ciliary dyskinesia.
- Nasal nitric oxide test (nNo)
- Assessment of ciliary ultrastructure by Transmission Electron Microscopy(TEM), Gold standard.
- Ciliary beat frequency CBF and Ciliary beat pattern CBP.
- Radio-aerosol MCC
- Direct video cinematography or oscillography to analyse ciliary beat waveform.
- Bronchial ciliary biopsy.
- Electron microscopy Tomography.
- Semen analysis.
History and Symptoms
Patients with primary ciliary dyskinesia may present in early infancy with respiratory distress or later in life with chronic bronchitis, persistent rhinorrhea, sinusitis, bronchiectasis, or male infertility.
Physical Examination
Primary ciliary dyskinesia PCD has no characteristic physical examination findings, however, any clue to recurrent sinus infections or respiratory distress should raise concern for diagnosing PCD.
Laboratory Findings
There are no diagnostic laboratory findings associated with primary ciliary dyskinesia.
Electrocardiogram
Primary ciliary dyskinesia occasionally presents with dextrocardia and situs inversus totalis, non functioning cilia in the embryonal node could be responsible for this mal positioning. Ecg shows right axis deviation, a finding if present should warrant further testing.
X-ray
An anterior-posterior or lateral chest x-ray could be helpful in diagnosing changes associated with chronic bronchitis and bronchiectasis in primary ciliary dyskinesia. Additionally, if dextrocardia is present it ca also be found on chest x-ray.
Echocardiography and Ultrasound
CT scan
Patients with primary ciliary dyskinesia (PKD) present with bronchiectasis or chronic sinusitis as the initial presentation which in turn leads to further testing and establishing a diagnosis. A High-resolution CT scan is the most sensitive imaging test to diagnose bronchiectasis but it can not differentiate between different aetiologies as bronchiectasis due to PCD vs Cystic fibrosis. HRCT can also interpret dextrocardia if present. If a chest X-ray in any patient is suspicious of bronchiectasis HRCT should be performed to rule out PCD.
MRI
MRI scans can assess ventilation defects in patients with primary ciliary dyskinesia PCD, along with dextrocardia if present.
Other Imaging Findings
There are no other imaging findings associated with Primary Ciliary Dyskinesia.
Other Diagnostic Studies
There are no other diagnostic studies associated with Primary Ciliary Dyskinesia.
Treatment
There are no definite treatment options, the goal is to manage associated conditions that can lead to worsening of PCD.
Medical Therapy
There are no definite treatment options to cure Primary ciliary dyskinesia PCD, the goal is to manage associated conditions that can lead to worsening of PCD such as antibiotics for infections, breathing exercises, spirometry for improved lung function, and drainage of secretions.
Interventions
There are no established interventions for Primary Ciliary Dyskinesia.
Surgery
Chronic rhino-sinusitis can predispose to superinfections with Pseudomonas aerurginosa in patients with primary ciliary dyskinesia PCD, endoscopic sinus drainage could facilitate sinus drainage. There is no evidence that suggests the insertion of tympanostomy tubes in cases of recurrent otitis media or otitis media with effusion therefore, regular doctor appointments should be scheduled in order to diagnose conductive hearing loss.
Primary Prevention
There are no established measures for the primary prevention of primary ciliary dyskinesia.
Secondary Prevention
There are no established measures for the secondary prevention of Primary Ciliary Dyskinesia PCD.