Upper Respiratory Tract Involvement in Primary Ciliary Dyskinesia: Genetics and Developmental Abnormalities

Primary ciliary dyskinesia (PCD) is a genetic disorder caused by abnormal function, and anatomy of the epithelial cilia. The abnormality in the cilia can result in nonmotile or abnormally motile cilia. The estimated incidence ranges from 1:7500 to 1:20,000 (Hannah WB, Lancet Respir Med 10:459–468, 2022). Normal beating function of cilia clears the mucus, microorganisms, and particles from the airways. Abnormal beating patterns, ultrastructural defects, and reduced number/absence of the cilia reduce mucociliary clearance of airways, resulting in chronic and recurrent upper and lower respiratory tract infections. The different types of cilia that are found in different parts of the body are involved in a variety of processes such as the proper function and alignment of organs in the body (Fliegauf M, Nat Rev Mol Cell Biol 8:880–893, 2007, Horani A, Pediatr Res 75:158–164, 2014). The importance of ciliary function in the respiratory system was recognized with the identification of Kartgener’s syndrome (KS) characterized by nodal ciliary dysfunction. The ultrastructural defect of the cilia was first identified by electron microscopy of immotile spermatozoa in brothers with KS, which showed the absence of dynein arms (Afzelius BA, J Cell Biol 5:269–278, 1959). Disorders of nodal cilia can lead to conditions such as laterality defects during embryogenesis, infertility due to defects in the reproductive organs (sperm, vas deferens, and/or fallopian tubes), and hydrocephalus due to defects in the ependymal cilia movements in the central nervous system.