The Genetics of Primary Ciliary Dyskinesia - Advances and Limitations

Primary ciliary dyskinesia (PCD) is a genetic condition that is caused by variants in genes associated with motile cilia. Most individuals with PCD present early in life with symptoms of chronic cough, nasal congestion, and recurrent upper and lower respiratory tract infections. About 50% of patients have laterality defects and cardiac malformation including heterotaxy syndrome, and most individuals have sub-infertility.

This narrative review synthesizes available evidence on the genes associated with PCD with emphasis on the differences in the effects on cilia structure and function.

Pathogenic variants in over 60 genes cause PCD. Many of these genes encode structural components within the ciliary axoneme, while others encode cytoplasmic assembly and regulatory proteins crucial for the normal function of cilia. Recent identification of variants in genes that are associated with both motile and sensory cilia function have expanded our understanding of the clinical manifestations of ciliopathies. Genetic confirmation is encouraged by the recent European Respiratory and American Thoracic societies diagnostic guidelines. The expanded use of genetic approaches and identification of variants of unknown significant in many genes associated with PCD emphasize the need for better diagnostic tools for PCD.

PCD is a complex genetic condition. Recognizing the clinical symptoms associated with PCD and establishing a genetic diagnosis is crucial for early initiation of proper treatment and for differentiating PCD from other conditions with similar symptoms.