Primary ciliary dyskinesia (PCD) is a rare disease of childhood and the original ciliopathy to be identified. It leads to a variety of clinical manifestations, which often lead to a fatal outcome in early life.
Early Signs and Symptoms
The clinical features in PCD are due to three contributory factors, namely:
- Abnormal structure, function, or assembly of cilia which prevent the clearance of mucus and bacteria from the respiratory tract, causing chronic infections of the ears, the sinuses and the lungs such as bronchitis, bronchiectasis and sinusitis
- Abnormal flagellar anatomy leading to infertility defects as a result of sperm hypomotility
- Failure to establish normal left-right asymmetry during embryonic development resulting in situs inversus and congenital heart defects
The first time that the combination of bronchiectasis was reported in association with situs inversus was way back in 1904, by Zivert. This syndrome was recognized more frequently from that time onward, and is today called PCD or Kartagener’s syndrome.
The phenotypic severity and rate of progression varies from patient to patient, but more than three in every four neonates with this condition will require oxygen supplementation at birth to ease neonatal respiratory distress.
Chronic sinusitis and airway infections are prominent in this group, with organisms such as Hemophilus influenzae and Streptococcus pneumoniae at first, but with Pseudomonas aeruginosa superseding them after early childhood. Even in infancy, these children have nasal congestion, with constant nasal discharge, resulting in very frequent sinus infections.
As a result of poor mucociliary clearance and infection, bronchiectasis is an inevitable sequel in adult life or even earlier. Some patients also develop lung calcifications which are sometimes expectorated, a phenomenon called lithoptysis.
Ear infection usually is present early in life but may be less in school-aged children. Chronic otitis media may produce hearing loss during each episode, which adversely affects the development of speech, and may end in permanent deafness.
The usual outcome is end-stage pulmonary disease which is successfully treated only by lung transplantation. The age at which this occurs may be delayed by prompt and adequate treatment of airway infections following a timely diagnosis.
Male infertility is a given in PCD due to the lack of sperm flagella. Females with PCD may or may not have reduced fertility, but following conception, the risk of ectopic gestation is higher because of lack of adequate ciliary function within the oviducts.
The absence or defect in ciliary function may result in any of the following:
Situs inversus totalis, present in almost half of all affected individuals, which refers to the complete inversion of the side of all viscera, but has no observable adverse effects.
Situs ambiguous or heterotaxy, present in about 12% of PCD individuals, consists of the lateral misplacement of one or a few organs but not all, being categorized as asplenia or polysplenia (no or multiple spleens respectively due to predominant right or left isomerism). Cardiac anomalies often occur, such as transposition of the great vessels or atrial isomerism. Pulmonary isomerism includes right or left isomerism, which means both lungs may resemble either the right or left normal lung respectively. The liver, stomach, intestine, brain, or skeletal structures may also be involved in this malrotation. There is thus a great variation in the presentation of heterotaxy.
This is a rare complication of PCD but has been known to occur, probably due to ciliary abnormality.