Choanal atresia and stenosis: Development and diseases of the nasal cavity

Abstract

Proper craniofacial development in vertebrates depends on growth and fusion of the facial processes during embryogenesis. Failure of any step in this process could lead to craniofacial anomalies such as facial clefting, which has been well studied with regard to its molecular etiology and cellular pathogenesis. Nasal cavity invagination is also a critical event in proper craniofacial development, and is required for the formation of a functional nasal cavity and airway. The nasal cavity must connect the nasopharynx with the primitive choanae to complete an airway from the nostril to the nasopharynx. In contrast to orofacial clefts, defects in nasal cavity and airway formation, such as choanal atresia (CA), in which the connection between the nasal airway and nasopharynx is physically blocked, have largely been understudied. This is also true for a narrowed connection between the nasal cavity and the nasopharynx, which is known as choanal stenosis (CS). CA occurs in approximately 1 in 5,000 live births, and can present in isolation but typically arises as part of a syndrome. Despite the fact that CA and CS usually require immediate intervention, and substantially affect the quality of life of affected individuals, the etiology and pathogenesis of CA and CS have remained elusive. In this review I focus on the process of nasal cavity development with respect to forming a functional airway and discuss the cellular behavior and molecular networks governing this process. Additionally, the etiology of human CA is discussed using examples of disorders which involve CA or CS. This article is categorized under: Signaling Pathways > Cell Fate Signaling Comparative Development and Evolution > Model Systems Birth Defects > Craniofacial and Nervous System Anomalies

Novel insights into the development of the avian nasal cavity

“…Obstruction of the nasal passages can occur via blockage of the choanae, external nares, or both (Buchtova, Boughner, Fu, Diewert, & Richman, 2007; Diewert & Shiota, 1990). The closure and subsequent reopening of the mammalian choana is well studied due to its association with choanal atresia, a condition that co‐occurs with a number of craniofacial syndromes, where the choanae fail to reopen and thus nasal respiration is obstructed (Kurosaka, 2019). Obstruction of the external nares, however, has received relatively less attention and is thought to occur through the formation of transient epithelial nasal plugs, both in reptiles (Buchtova et al, 2007; Howes & Swinnerton, 1901) and mammals (Alomaisi, El‐Ghazali, Nosseur, Ahmed, & Konsowa, 2018; Bollert & Hendrickx, 1971; Kim et al, 2004; Nishimura, 1993; Wassif et al, 2001), with no recorded cases in avian embryos.…”

Unilateral Choanal Atresia: Indications of Long-Term Olfactory Deficits and Volumetric Brain Changes Postsurgically

“…This malformation can occur unilaterally or bilaterally, with the latter being relatively less common [4]. Moreover, it is known to co-occur with a number of other disorders, the most common of which is CHARGE (coloboma, heart defects, atresia choanae, retarded growth, genitourinary abnormalities, and ear anomalies/ deafness) syndrome [5].…”

Synergistic role of retinoic acid signaling and Gata3 during primitive choanae formation

“…Although the etiology and pathogenesis of cleft lip and/or palate are relatively well investigated (2), the developmental origins of many craniofacial anomalies are not well understood at either the molecular or cellular level. Choanal atresia (CA) is a craniofacial malformation characterized by a blocked nasal airway (3,4). The incidence of CA is 1 in 5000 live births, and in cases of bilateral CA can be lethal.…”

“…Although theoretical mechanisms have been proposed to explain the basis of choanal atresia, very little basic research using animal models has been performed, and conclusive answers have not been provided (6). It is well known that CA can occur in concert with various genetic disorders such as CHARGE syndrome and Crouzon syndrome (3). This indicates that multiple genetic pathways may underlie the development of primitive choanae formation and furthermore that disruption of these signaling pathways could result in CA.…”