Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a congenital disorder of children, caused by a variety of genetic mutations. It is thus a heterogeneous disorder, with the same clinical manifestations being capable of being caused by multiple causes. It is associated with autosomal recessive mutations in several different genes.

It was first reported in 1904 as a combination of situs inversus with bronchiectasis. Later, the classical triad was established, consisting of chronic sinusitis, bronchiectasis, and situs inversus, known as Kartagener’s syndrome. Much later, this was known to be the result of defects in the structure and function of the microscopic subcellular structures known as cilia. These normally motile and rhythmically moving structures become either immotile (rare) or display a stiff arrhythmic beat which does not produce the desired effects.

The prevalence of PCD is about 1 in 16 000 births. This is probably lower than the real prevalence.

Clinical Manifestations

PCD has been observed to be associated with a variety of signs and symptoms, such as chronic sinusitis, lung infections, chronic bronchitis, chronic bronchiectasis, and situs inversus or situs ambiguous. The phenotypic severity of the disorder in different patients varies, probably according to the genotype.

The lack of ciliary function leads to poor mucociliary clearance, with mucus accumulation in the airways leading to constant nasal congestion and discharge, from infancy onward. This is accompanied by a chronic cough. Organisms such as Hemophilus influenzae and Streptococcus pneumoniae, followed by Pseudomonas aeruginosa in early adolescence, colonize the mucus resulting in chronic lung infections in the form of bronchitis. This leads to bronchiectasis, a condition which produces dilated sacculated small airways associated with infection, which can be life-threatening.

In addition, PCD patients often have situs inversus, in which the internal organs are reversed in laterality from left to right. While this is not associated with any known adverse effects, the related condition called situs ambiguous is linked to serious and often fatal outcomes. Asplenia or polysplenia, and isomerism of the lungs or intestine, are all known to occur in situs ambiguous, with severe and complex cardiac defects.

Males with PCD are almost invariably infertile due to the absence of sperm flagella, while females are less commonly affected in this manner. However, ectopic gestation may occur.

Complications of PCD include respiratory difficulties and end-stage respiratory failure, permanent hearing loss due to recurrent otitis media, and rarely, hydrocephalus.

Up to a third of all PCD cases are caused by mutations in two genes, DNAI1 and DNAH5, but up to 27 genes have been found to harbor a range of mutations in this condition. A third of cases have no identifiable known mutation.

Diagnosis is on the basis of the typical clinical characteristics, assisted by sputum cultures, chest and sinus X-rays or CT scans, and pulmonary function tests. Hearing evaluation and other genetic tests may be offered. Treatment is empiric and symptomatic, including measures to improve mucus clearance and treat respiratory infections. Routine immunizations are a must in these patients. Nasal nitric oxide measurement shows that it is abnormally low in patients who have PCD. Genetic testing is offered to these patients.

References

1. https://www.nature.com/gim/journal/v11/n7/full/gim200967a.html
2. https://www.ncbi.nlm.nih.gov/books/NBK1122/
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4864047/
4. http://jmg.bmj.com/content/early/2014/10/28/jmedgenet-2014-102755