Primary ciliary dyskinesia (PCD)

Symptoms include neonatal respiratory distress, chronic upper and lower respiratory tract disease, infertility, and situs anomalies. About 50% of patients exhibit situs abnormalities, which may be associated with congenital heart defects. Clinical features are often subtle and highly variable, making diagnosis challenging.

The prevalence of PCD is difficult to determine due to historical lack of standardised diagnostic approaches but is estimated at approximately 1:10,000–1:20,000.

Pathogenic variants have been identified in more than 30 genes associated with PCD and Kartagener syndrome. Most causative variants are loss-of-function (nonsense, frameshift, or defective splice site variants). Missense variants may also be observed, although distinguishing pathogenic variants from rare benign changes can be difficult. Most variants are private, and clustering in specific gene regions is less common.

PCD is inherited in an autosomal recessive pattern.

Diagnosis is complicated by the subtlety and variability of clinical features. Modern sequencing methods allow the identification of biallelic pathogenic variants in approximately 70% of affected individuals.

The term heterotaxy is used for patients with isolated situs inversus of varying degrees. Heart defects and other organ malformations, such as asplenia or polysplenia, are also often observed. When PCD occurs with laterally inverted internal organs, it is referred to as Kartagener syndrome.

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