Primary ciliary dyskinesia is an autosomal recessive genetic disorder that can be congenital or acquired, affecting the functioning of cilia lining the respiratory tract and fallopian tubes. The immotility of cilia is due to a deficiency in dynein arms of the cilia. These immotile cilia are also present in other areas with cilia, specifically in the inner ear and sperm ducts. Therefore, patients often exhibit chronic recurrent sinusitis, middle ear infections, deafness, infertility, lung inflammation, and bronchiectasis. Approximately 50% of PCDs patients have situs inversus. When situs inversus is present along with sinusitis and bronchiectasis, it is known as KS  [7,8,9].

The normal ciliary function is crucial for protecting the respiratory tract, sperm motility, and proper positioning of organs during embryonic development. Deficiencies or abnormalities in the dynein arms, radial spokes, and microtubules of the cilia, encoded by mutated DNAI1 and DNAH5 genes, have been identified as structural and functional anomalies that lead to impaired ciliary function. Abnormal ciliary motion at different sites leads to recurrent respiratory infections, infertility, and situs inversus  [4,5,6].

The recommended diagnostic criteria for this syndrome include a history of bronchial infection and chronic rhinosinusitis since childhood, combined with one or more of the following characteristics: (a) situs inversus or right-sided heart in the patient or siblings, (b) live but immotile sperm, (c) loss or reduced ability of mucociliary clearance in the bronchi, and (d) ciliary ultrastructural defects observed under electron microscopy  [10,11,12]. Laboratory screening tests include measuring nitric oxide levels in exhaled breath and conducting a saccharin test to evaluate mucociliary function in the nasal mucosa. High-speed video microscopy is used to assess the frequency and pattern of ciliary motion, while transmission electron microscopy is used to detect structural defects in cilia. Genetic testing to identify mutations in DNAI1 and DNAH5 genes is also conducted in the laboratory for definitive diagnosis. Abnormalities observed include reduced nasal nitric oxide concentration (approximately 10% of normal levels), prolonged saccharin clearance time (>1 hour), decreased ciliary beat frequency (<11 Hz/second), and defects in ciliary ultrastructure (dynein arms) and mutated DNAI1 and DNAH5 genes [5]. In a clinical setting, it is important to differentiate KS from Young syndrome, a rare genetic disorder similar to KS, which typically affects middle-aged males with chronic sinusitis, infertility due to azoospermia, and bronchiectasis. Individuals with this disorder have normal lung function but tend to secrete thick, viscous mucus, increasing the risk of pulmonary infections. The process of sperm production is normal, but reduced fertility is attributed to impaired transport of sperm through the reproductive tract  [9,13].

All three of our patients had a history of sinusitis, recurrent respiratory infections since childhood, bronchiectasis, and situs inversus observed in imaging. The two male patients exhibited more severe clinical symptoms and progression. The first patient experienced multiple episodes of severe respiratory infections, which negatively affected his overall health and quality of life. Lung function declined rapidly, leading to early onset respiratory failure, occurring only 8 years after the disease was diagnosed. The patient now depends entirely on medical support and is infertile. The second patient shows a slower progression with fewer respiratory tract infections, and the decline in lung function occurs at a slower rate. After 15 years from the time of diagnosis, the patient presents with chronic respiratory failure with CO₂ retention, and their overall condition is better. Particularly, the second patient has normal reproductive function.

In the third patient, lung damage is minimal and there have been almost no respiratory tract infections throughout the course of the disease up to the present time. Besides the symptoms of allergic rhinosinusitis, the patient is entirely healthy and does not exhibit any signs of respiratory tract infection. CT imaging of the lungs also shows very little bronchiectasis. The patient also has normal reproductive function. However, they are also diagnosed with bronchial asthma. Thus, there are clear differences in respiratory symptoms, disease progression, and reproductive function among the three patients. This may be related to the extent of structural damage and functional impairment of the target organs. Moreover, in female patients with KS, the degree of damage to target organs such as the lungs and reproductive system may be milder compared to male patients. On the other hand, the third patient is a female and has not been exposed to cigarette smoke, which differentiates her from the male patients, and cigarette smoke could be a risk factor for the progression of lung damage in KS patients. However, further studies with larger sample sizes are needed in the future to substantiate this hypothesis. Furthermore, the possibility of reproductive capacity in KS patients is rare. This can be explained by the potential heterogeneity through intermediate genetic influences on phenotypic expressions  [2].

The standard respiratory treatment for patients with KS includes the use of antibiotics (preferably those with good coverage against Pseudomonas). The effectiveness of DNase and other mucolytic agents such as hypertonic saline and acetylcysteine has not been fully evaluated in these patients, but they can be used, especially in patients with recurrent infections or ongoing respiratory symptoms. Respiratory physical therapy, oxygen therapy, and non-invasive ventilation should be considered in cases of respiratory failure with CO₂ retention [12]. Low-dose prolonged prophylactic antibiotics should be administered in individuals who frequently experience acute exacerbations of bronchiectasis (≥ 3 times per year). Routine vaccination against influenza and pneumococcus is highly effective in preventing respiratory infections in these patients  [12,14]. It is particularly important to avoid exposure to harmful agents such as cigarette smoke. Despite having a slower progression of respiratory failure compared to case 1 and case 2 experienced respiratory failure at an early stage when compared to patients with chronic obstructive pulmonary disease and respiratory failure  [4,15,16,17]. In our two male patients, both of whom had extensive bronchiectasis in both lungs, sputum cultures consistently revealed infection with multidrug-resistant gram-negative bacteria. Thus, gram-negative bacterial infections are commonly observed in KS patients with significant bronchiectasis.