Primary ciliary dyskinesia and associated sensory ciliopathies

Abstract

Primary ciliary dyskinesia (PCD) is a genetic disease of motile cilia, which belongs to a group of disorders resulting from dysfunction of cilia, collectively known as ciliopathies. Insights into the genetics and phenotypes of PCD have grown over the last decade, in part propagated by the discovery of a number of novel cilia-related genes. These genes encode proteins that segregate into structural axonemal, regulatory, as well as cytoplasmic assembly proteins. Our understanding of primary (sensory) cilia has also expanded, and an ever-growing list of diverse conditions has been linked to defective function and signaling of the sensory cilium. Recent multicenter clinical and genetic studies have uncovered the heterogeneity of motile and sensory ciliopathies, and in some cases, the overlap between these conditions. In this review, we will describe the genetics and pathophysiology of ciliopathies in children, focusing on PCD, review emerging genotype-phenotype relationships, and diagnostic tools available for the clinician.

Olfactory dysfunction is worse in primary ciliary dyskinesia compared with other causes of chronic sinusitis in children

“…Cilia are evolutionary conserved organelles subdivided into primary (non-motile, with multiple signalling and sensory functions), nodal (defining situs) and motile (propelling mucus across epithelia) 1. There is more overlap than hitherto appreciated between primary and motile ciliopathies 2.…”

To beat, or not to beat, that is question! The spectrum of ciliopathies

“…Each individual ciliopathy is rare (from 1 in 1000 to 1 in 150 000), but collectively the incidence is up to 1 in 2000 . Ciliopathies are usually classified into sensory (or primary) and motor ciliopathy syndromes . However, a wide range of genetic and phenotypic overlap exists between sensory and motor ciliopathy syndromes, with considerable genetic heterogeneity …”

“…Non‐motile cilia serve as receptors, sensing a wide variety of extracellular signals, and are linked to various signaling pathways . Non‐motile cilia are also associated with the regulation of planar cell polarity .…”

“…They have key roles in cell locomotion, mucus or water propulsion, sexual reproduction, embryonic development, signaling, organ function, and homeostasis . Human cilia are usually classified into motile and non‐motile cilia (Figure ), and ciliopathies into motor and sensory ciliopathies . Primary ciliary dyskinesia (PCD), the best known ciliopathy in humans, is caused by a primary defect in motile cilia found on the epithelium of the respiratory tract, which leads to impaired mucociliary clearance in the upper and lower airways, and to significant sinopulmonary disease …”

Síndrome de Kartagener: reporte de un caso y revisión de la literatura

“…Normalmente, los cilios se mueven de manera sincrónica y rítmica a una frecuencia de alrededor 8 a 12 Hz (a temperatura ambiente), movimiento que es crítico para desplazar los fluidos a través de las vías aéreas [5].…”