Mini-Symposium: Primary Ciliary DyskinesiaPrimary ciliary dyskinesia: when to suspect the diagnosis and how to confirm it
Section snippets
Historical background
Although Sievert first described the triad of sinusitis, bronchiectasis and situs inversus, and Kartagener recognized it as a genetic entity, ciliary immotility was first described by the electron microscopist Afzelius in the 1970s.7 Afzelius first reported immotile cilia in the sperm tails of infertile males, some cases occurring in the same family, and half of these also had the triad associated with Kartagener syndrome. This observation was soon applied by Sturgess,8, 9 another electron
Cilial structure and function
Cilia are complex and highly specialized organelles made up of over 360 proteins.10 The respiratory cilia are about 6 μm long and 200−250 nm in diameter. Each respiratory cilium is composed of microtubules arranged in a 9+2 formation, with nine peripheral microtubule pairs arranged around a central pair. This is known as an axoneme. The peripheral pairs consist of a complete microtubule, the A tubule, and a partial B microtubule. These pairs are connected to their neighbouring microtubular pairs
Ultrastructural abnormalities
Several ultrastructural defects have been identified in patients with PCD. Most common are those affecting the dynein arms, in particular the outer arms, but abnormalities in almost any part of the axonemal structure can occur. A range of such ultrastructural defects can be seen in Fig. 2. The various known ultrastructural defects are given in Table 1 and are listed in order of their reported frequency.4, 8, 11 Rarely, there is complete absence of cilia, a condition called ciliary aplasia, the
Genetics
PCD is nearly always inherited as an autosomal recessive disorder, although rarely there have been cases of X-linked or autosomal dominant inheritance.15, 16 The axoneme is made up of hundreds of different proteins and therefore the number of genes involved is by necessity very large. The genetic heterogeneity of PCD has made the identification of gene mutations a laborious process,17 although five recessive gene mutations have now been identified. These mutations, DNAH5, DNAH11, DNAI1, DNAI2
When to suspect primary ciliary dyskinesia: clinical signs and symptoms
In the absence of specific findings, such as situs inversus, the presentation in PCD is often non-specific. Common childhood conditions such as upper respiratory tract infections, rhinitis and middle ear pathology are so typical in the preschool child that consideration of PCD may be delayed and late referral is common. One review of 55 patients diagnosed at a tertiary referral centre records the median age at referral to be 4 years.5 There is little evidence that early diagnosis improves
Diagnostic testing for Primary Ciliary Dyskinesia
PCD is usually considered as one of a number of differential diagnoses, unless absolutely typical features of PCD are present. Therefore, investigations to exclude other more common conditions have often been undertaken during the initial phase of the work-up. These investigations may include sweat test, immunological investigation and exclusion of gastro-oesophageal reflux and pulmonary aspiration amongst others. Following the exclusion of other causes, or where typical features of PCD exist,
Conclusion
Although PCD could once be considered a rare and, perhaps, overlooked condition, the tide has turned and readily available diagnostics and treatment in specialized centres have led to a surge in interest in this best known of the ciliopathies. PCD is an important cause of progressive lung disease and a key aim of any paediatric respiratory unit must be to establish an early diagnosis and introduce treatment strategies prior to the onset of bronchiectasis. In the majority of cases, diagnostic
Practice points
- 1.
Presentation in PCD is often non-specific, or has features typical of many childhood illnesses. A high index of suspicion should be exercised when examining patients with prolonged or unremitting symptoms of both upper and lower airway infection.
- 2.
PCD is an important cause of progressive lung disease and our key aim is to establish an early diagnosis and institute treatment strategies prior to the onset of irreversible lung damage.
- 3.
Patients presenting with ‘difficult’ asthma or other conditions
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Cited by (39)
Respiratory muscle strength, exercise capacity and physical activity in patients with primary ciliary dyskinesia: A cross-sectional study
2022, Respiratory MedicineCitation Excerpt :Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder characterized by abnormal ciliary motion and impaired mucociliary clearance [1].
Diagnostic Pathology: Head & Neck
2017, Diagnostic Pathology: Head and NeckEstablishing normative nasal nitric oxide values in infants
2015, Respiratory MedicineCitation Excerpt :Nasal NO values obtained by such tidal breath sampling has shown good reliability, sensitivity, and high within-subject repeatability [11–14]. As methods for nNO measurement have become standardized, and nNO cutoff values established and validated for PCD, nNO is becoming a useful screening tool for PCD assessments [6,13,15,16]. The PCD level nNO cutoff values are stratified by age, given nNO levels normally rise with age.
Primary Ciliary Dyskinesia: Clinical Criteria Indicating Ultrastructural Studies
2013, Archivos de BronconeumologiaCyanotic Episodes in an Infant With Known Situs Inversus: Indications for an Apparent Life-Threatening Event Evaluation
2012, Journal of Pediatric Health CareCitation Excerpt :Bronchiectasis is a sign of progressive disease and airway obstruction (Leigh et al., 2009). Issues with fertility are common in both genders because of impaired sperm motility and egg propulsion through the fallopian tubes (Hogg, 2009). PCD occurs in 1 in 12,000 to 20,000 live births (Lie et al., 2010).