Septal chondrocyte hypertrophy contributes to midface deformity in a mouse model of Apert syndrome

Bong-Soo Kim,Heein Yoon,Hye-Rim Shin,Hyun-Jung Kim,Hyun-Mo Ryoo,Woo-Jin Kim,Young-Dan Cho,Kang-Young Choi,Je-Yong Choi

doi:10.1038/s41598-021-87260-5

Abstract

Midface hypoplasia is a major manifestation of Apert syndrome. However, the tissue component responsible for midface hypoplasia has not been elucidated. We studied mice with a chondrocyte-specific Fgfr2S252W mutation (Col2a1-cre; Fgfr2S252W/+) to investigate the effect of cartilaginous components in midface hypoplasia of Apert syndrome. In Col2a1-cre; Fgfr2S252W/+ mice, skull shape was normal at birth, but hypoplastic phenotypes became evident with age. General dimensional changes of mutant mice were comparable with those of mice with mutations in EIIa-cre; Fgfr2S252W/+, a classic model of Apert syndrome in mice. Col2a1-cre; Fgfr2S252W/+ mice showed some unique facial phenotypes, such as elevated nasion, abnormal fusion of the suture between the premaxilla and the vomer, and decreased perpendicular plate of the ethmoid bone volume, which are related to the development of the nasal septal cartilage. Morphological and histological examination revealed that the presence of increased septal chondrocyte hypertrophy and abnormal thickening of nasal septum is causally related to midface deformities in nasal septum-associated structures. Our results suggest that careful examination and surgical correction of the nasal septal cartilage may improve the prognosis in the surgical treatment of midface hypoplasia and respiratory problems in patients with Apert syndrome.

Highlights

Midface hypoplasia is a major manifestation of Apert syndrome
These results indicated that the presence of the Fgfr2S252W mutation in the cartilaginous tissues was more responsible for the early midfacial deformities than that in mature osteoblasts
In patients with Apert syndrome, midface hypoplasia and airway obstruction are the major problems that must be managed during c hildhood[6]

Summary

Introduction

Midface hypoplasia is a major manifestation of Apert syndrome. the tissue component responsible for midface hypoplasia has not been elucidated. We carefully observed mice with the chondrocyte-specific Fgfr2S252W mutation to examine the growth of facial cartilaginous tissues and its effect on midface hypoplasia. Histological observation in the midsagittal plane of the facial region showed the fusion between the premaxilla and the vomer in EIIa-SW and Col2-SW mice (Fig. 2b).

Results

Conclusion