Choanal Atresia and Craniosynostosis: Development and Disease

Abstract

A number of textbooks, review articles, and case reports highlight the potential comorbidity of choanal atresia in craniosynostosis patients. However, the lack of a precise definition of choanal atresia within the current craniosynostosis literature and widely varying methods of detection and diagnosis have produced uncertainty regarding the true coincidence of these conditions. The authors review the anatomy and embryologic basis of the human choanae, provide an overview of choanal atresia, and analyze the available literature that links choanal atresia and craniosynostosis. Review of over 50 case reports that describe patients diagnosed with both conditions reveals inconsistent descriptions of choanal atresia and limited use of definitive diagnostic methodologies. The authors further present preliminary analysis of three-dimensional medical head computed tomographic scans of children diagnosed with craniosynostosis syndromes (e.g., Apert, Pfeiffer, Muenke, and Crouzon) and typically developing children and, although finding no evidence of choanal atresia, report the potentially reduced nasal airway volumes in children diagnosed with Apert and Pfeiffer syndromes. A recent study of the Fgfr2c Crouzon/Pfeiffer syndrome mouse model similarly found a significant reduction in nasal airway volumes in littermates carrying this FGFR2 mutation relative to unaffected littermates, without detection of choanal atresia. The significant correlation between specific craniosynostosis syndromes and reduced nasal airway volume in mouse models for craniosynostosis and human pediatric patients indicates comorbidity of choanal and nasopharyngeal dysmorphologies and craniosynostosis conditions. Genetic, developmental, and epidemiologic sources of these interactions are areas particularly worthy of further research.

Figures

Figure 1

3DCT reconstruction of the cranium of a typically developing child viewed from below showing the osteological borders of the choanae: vomer (blue), sphenoid body (pink), medial pterygoid plates (red), and horizontal plates of the palatine bones (purple).

Figure 2

Mid-sagittal section of adult human showing the position of the choanae relative to the human nasal, oral, and pharyngeal airways.

Figure 3

Formation of the secondary palate and choanae. Inferior view of the forming palate showing (left) vertically oriented palatal shelves, (center) the palatal shelves as they rotate downward into a horizontal position and begin to approximate one another to form the primary choanae, and (right) fused palatal shelves in their final orientation, with the incisive foramen at the intersection of the primary and secondary palate and the secondary, or definitive, choanal openings at the posterior end of the palate. (Adapted from 3)

Figure 4

Nasal airway segmented from CT image of a typically developing child at 10 months, as an example of how the nasal airway volume data presented in Figure 5 were collected. Top Left) Axial CT image at the level of the orbits indicating area of close-up (red box) for three additional anatomical levels including: Top Right) the nasal cavity (red) with soft tissue of the nose bordering the anterior nares at the level of the maxillary sinuses; Bottom Left) mid-nares level with partial soft tissue border of the anterior nares; and Bottom Right) at the level of the alveolar processes of the maxillae showing the nasopharyngeal lumen (red) anterior to a line (blue) connecting the most posterior points on the medial plates of the pterygoid bone.

Figure 5

Scatterplot of total nasal airway volume and age (in months) of individuals diagnosed with various craniosynostosis syndromes and typically developing individuals. Sample sizes are as follows: Apert (n = 13), Crouzon (n = 10), Muenke (n = 5), Pfeiffer (n = 5), unaffected (n = 39). Lines representing the results of regression analysis showing the relationship between age and total nasal airway volume (including the ethmoidal air cells) for each group. It is important to note that this plot and the regression lines estimated from the cross-sectional data are used to demonstrate the variation in nasal airway volumes among craniosynostosis syndromes. As the nasal airway volume data are based on cross-sectional datasets for each diagnostic category, these regression lines do not necessarily indicate growth patterns or growth trajectories.

Figure 6

3DCT reconstruction of a typically developing child (left) showing superimposed segmentations of skin surface (beige), brain surface (grey) and upper airway lumen (blue). At right are “virtual endocasts” of the nasopharynx of a child with Apert syndrome (pink, at left) and a typically developing child (maroon, at right) as segmented from high resolution 3DCT. Superimposition of the two virtual endocasts (center) shows local areas of greatest shape difference. This comparison is not a statistical comparison of the nasopharyngeal anatomy of patients with Apert syndrome and typically developing individuals; rather, this superimposition provides an example of how nasopharyngeal morphology of craniosynostosis patients may differ from typically developing individuals.

Figure 7

3DCT reconstruction of the cranium of 6 week old C57BL/6J mouse showing the bones that form the osteological borders of the choanae in the human skull: vomer (blue), basisphenoid (pink), medial pterygoid plates (red), and horizontal plates of the palatine bones (purple). The vomer (which is ghosted in this illustration) lies deep to the maxillae and so is hidden in an inferior view. The presphenoid is shown in green. Note the anatomical separation of these bones compared to the human skull in Figure 1. The black arrow indicates the position of the choanae in mice at the soft tissue intersection of the posterior nasal cavity and nasopharynx.