Clinical and genetic aspects of primary ciliary dyskinesia/Kartagener syndrome

Abstract

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder of motile cilia. Most of the disease-causing mutations identified to date involve the heavy (DNAH5) or intermediate (DNAI1) chain dynein genes in ciliary outer dynein arms, although a few mutations have been noted in other genes. Clinical molecular genetic testing for PCD is available for the most common mutations. The respiratory manifestations of PCD (chronic bronchitis leading to bronchiectasis, chronic rhino-sinusitis and chronic otitis media) reflect impaired mucociliary clearance owing to defective axonemal structure. Ciliary ultrastructural analysis in most patients (>80%) reveals defective dynein arms, although defects in other axonemal components have also been observed. Approximately 50% of PCD patients have laterality defects (including situs inversus totalis and, less commonly, heterotaxy and congenital heart disease), reflecting dysfunction of embryological nodal cilia. Male infertility is common and reflects defects in sperm tail axonemes. Most PCD patients have a history of neonatal respiratory distress, suggesting that motile cilia play a role in fluid clearance during the transition from a fetal to neonatal lung. Ciliopathies involving sensory cilia, including autosomal dominant or recessive polycystic kidney disease, Bardet-Biedl syndrome, and Alstrom syndrome, may have chronic respiratory symptoms and even bronchiectasis suggesting clinical overlap with PCD.

Combined Occurrence of Alström Syndrome and Bronchiectasis

“…10,11 The axoneme structure of nasal mucosa of the patient is seen normal in the electron microscopy. Saccharin clearance time is normally 7 to 15 minutes.…”

Doppler Echocardiographic Changes in Respiratory Diseases

“…So; the ciliated epithelium situated in the airways, brain ventricles, oviducts, and vasa efferentia of the testes all may be affected. The classic syndrome is a triad of situs inversus, bronchiectasis, and sinusitis which was first described by Kartagener 1904 (Leigh et al 2009 Parmley et al 1958; found that the most commonly encountered cardiac lesion at necropsy was myocardial rupture of a septum or a chamber wall. Bjørnstad et al 2009 described a case with coronary artery dissection and acute myocardial infarction following blunt chest trauma.…”

Clinical care for primary ciliary dyskinesia: current challenges and future directions

“…The recently published European Respiratory Society (ERS) guidelines for the diagnosis of PCD provide recommendations on patient referrals [30]. Simple and easy-to-use predictive tools that provide disease probability scores, such as PICADAR (PrImary CiliARy DyskinesiA Rule) [3], and expert-defined clinical symptoms scores [10] will probably improve referrals from secondary care but require validation in different settings [26].…”