Primary ciliary dyskinesia (PCD) is associated with situs abnormalities, abnormal sperm motility, and abnormal ciliary structure and function that result in retention of mucus and bacteria in the respiratory tract leading to chronic oto-sino-pulmonary disease. More than 75% of full-term neonates with PCD have 'neonatal respiratory distress' requiring supplemental oxygen for days to weeks. Chronic airway infection, apparent in early childhood, results in bronchiectasis that is almost uniformly present in adulthood. Nasal congestion and sinus infections, apparent in early childhood, persist through adulthood. Chronic/recurrent ear infection, apparent in most young children, can be associated with transient or later irreversible hearing loss. Situs inversus totalis (mirror-image reversal of all visceral organs with no apparent physiologic consequences) is present in 50% of individuals with PCD; heterotaxy (discordance of right and left patterns of ordinarily asymmetric structures that can be associated with significant malformations) is present in approximately 6%. Approximately 50% of males with PCD are infertile as a result of abnormal sperm motility.
The diagnosis of PCD requires the presence of the characteristic clinical phenotype and either (1) specific ciliary ultrastructural defects identified by transmission electron microscopy in biopsy samples of the respiratory epithelium or (2) mutation in one of seventeen genes known to be associated with PCD: DNAI1, DNAAF3, DNAH5, HYDIN, NME8, DNAH11, DNAI2, DNAAF2 (C14orf104), RSPH4A, RSPH9, DNAAF1 (LRRC50), CCDC39, CCDC40, DNAL1, CCDC103, HEATR2, and LRRC6. Biallelic mutations in: DNAI1 account for approximately 2%-9% of all PCD; DNAH5 account for approximately 15%-21% of all PCD. Molecular genetic testing of fifteen of the known genes is available on a clinical basis.
PCD is inherited in an autosomal recessive manner. The parents of an affected individual are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes (carriers) are asymptomatic. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the disease-causing mutations in the family are known.