Primary ciliary dyskinesia: clinical presentation, diagnosis and genetics

Abstract

Primary ciliary dyskinesia (PCD) is a phenotypically and genetically heterogeneous disorder with an autosomal-recessive inheritance pattern. Only rarely other modes of inheritance such as X-linked transmission are observed. The disease phenotype is caused by defects of respiratory cilia, sperm tails and the cilia of the embryonic node. The lack of mucociliary clearance contributes to recurrent respiratory tract infections, that might progress to permanent lung damage (bronchiectasis). The goal of therapy is prevention of bronchiectasis. Male infertility due to sperm tail dysmotility is another frequent finding in PCD. Half of affected individuals have situs inversus (Kartagener's syndrome) due to randomization of left/right body asymmetry. Currently three genes (DNAI1, DNAH5, DNAH11) that encode for dynein proteins have been linked to recessive PCD. Mutations in RPGR located on the X chromosome have been identified in males with retinitis pigmentosa and PCD. As a screening test nasal nitric oxide (NO) measurement is widely used. Establishment of diagnosis currently relies on electron microscopy, direct evaluation of ciliary beat by light microscopy, and/or the novel method of high-resolution immunofluorecent analysis of respiratory cilia.