Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder characterized by unmotile, dysmotile or absent cilia. Symptoms include neonatal respiratory distress, chronic upper and lower respiratory tract diseases, infertility, and situs abnormalities, which occur in about 50% of PCD patients and may be associated with congenital heart defects. When PCD occurs with laterally inverted positioning of the internal organs, it is called Kartagener syndrome. The clinical features of PCD can be subtle and highly variable, making diagnosis difficult. The prevalence of PCD is difficult to determine, as there was no accessible, standardized diagnostic approach in the past, but is estimated to be around 1:10,000-1:20,000.
Pathogenic variants have been identified in more than 30 genes associated with PCD and Kartagener syndrome. Most of the changes leading to PCD are loss-of-function variants (nonsense, frameshift or defective splice sites). In some cases, missense variants are detected, although in these cases it is often difficult to distinguish disease-causing variants from rare benign changes. Most causal variants are private. Clustering of variants in specific gene regions, as is known to occur in other genetic disorders, is less common. With the help of modern sequencing methods, it is possible to identify disease-causing biallelic variants in about 70% of those affected.
The term heterotaxy is used for patients with isolated situs inversus of various degrees; heart defects and other organ malformations such as asplenia or polysplenia are also often observed.
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