Abstract

Craniofacial development is a highly regulated process in which the cranial base plays a key role in guiding the growth and spatial orientation of facial structures. Cranial base growth occurs primarily through endochondral ossification at cartilaginous joints known as synchondroses. The major midline synchondroses spheno-occipital, spheno-ethmoidal, and intersphenoidal function as intrinsic growth centers that contribute to anteroposterior elongation of the skull and positioning of the maxillofacial complex, exhibiting proliferative activity comparable to epiphyseal growth plates. This review summarizes the anatomy, histology, developmental biology, and molecular regulation of cranial base synchondroses, highlighting key signaling pathways such as the Indian Hedgehog–parathyroid hormone-related protein (Ihh–PTHrP) axis, fibroblast growth factor (FGF), bone morphogenetic proteins (BMPs), and Wnt/β-catenin signaling that regulate chondrocyte proliferation, differentiation, and endochondral ossification. Particular emphasis is placed on the spheno-occipital synchondrosis (SOS), which remains active until adolescence and plays a significant role in cranial base growth. Its maturation and fusion serve as useful indicators of skeletal maturity and have important implications for orthodontic diagnosis and the timing of growth-modifying therapies. Understanding the biology of cranial base synchondroses therefore enhances the assessment of craniofacial growth and supports more effective orthodontic treatment planning.

• 1.   Cendekiawan T, Wong RWK, Rabie ABM. Relationships Between Cranial Base Synchondroses and Craniofacial Development: A Review. Open Anat J. 2010 Apr 22;2(1):67–75.
• 2.   Capote R, Preston K, Kapadia H. Craniofacial Growth and Development. Oral and Maxillofacial Surgery Clinics of North America. 2023 Nov;35(4):501–13.
• 3.   Enlow DH, Hans MG. Essentials of facial growth. 2nd ed. Ann Arbor, MI: Distributed by Needham Press; 2008.
• 4.   Ingervall B, Thilander B. The Human Sphenooccipital Synchondrosis I. The Time of Closure Appraised Macroscopically. Acta Odontologica Scandinavica. 1972 Jan;30(3):349–56.
• 5.   Hsieh YL, Wei X, Wang Y, Zhang H, Qi S, Xie D, et al. Chondrocyte Tsc1 controls cranial base bone development by restraining the
• 6.   Smith TD, McMahon MJ, Millen ME, Llera C, Engel SM, Li L, et al. Growth and Development at the Sphenoethmoidal Junction in Perinatal
• 7.   Lei WY, Wong RWK, Rabie ABM. Factors Regulating Endochondral Ossification in the Spheno-occipital Synchondrosis. The Angle
• 8.   Bellon E, Luyten FP, Tylzanowski P. δ-EF1 is a negative regulator of Ihh in the developing growth plate. Journal of Cell Biology. 2009 Nov
• 9.   Wei X, Hu M, Mishina Y, Liu F. Developmental Regulation of the Growth Plate and Cranial Synchondrosis. J Dent Res. 2016
• 10.   Nie X. Cranial base in craniofacial development: Developmental features, influence on facial growth, anomaly, and molecular basis. Acta Odontologica Scandinavica. 2005 Jan;63(3):127–35
• 11.   Hallett SA, Ono W, Franceschi RT, Ono N. Cranial Base Synchondrosis: Chondrocytes at the Hub. IJMS. 2022 Jul 15;23(14):7817.
• 12.   Funato N. New Insights Into Cranial Synchondrosis Development: A Mini Review. Front Cell Dev Biol. 2020 Aug 11;8:706.
• 13.   Rignol G, Garcia S, Authier F, Smith K, Tosello L, Marsault R, et al. Longitudinal Imaging of the Skull Base Synchondroses Demonstrate
• 14.   Flaherty K, Singh N, Richtsmeier JT. Understanding craniosynostosis as a growth disorder. WIREs Developmental Biology. 2016 Jul;5(4):429–59.
• 15.   Sorice S, Bastidas N, Nah AHD, Bartlett SP, Taylor JA. Premature Fusion of the SphenoOccipital Synchondrosis (SOS) and Midface
• 16.   Tahiri Y, Paliga JT, Vossough A, Bartlett SP, Taylor JA. The Spheno-Occipital Synchondrosis Fuses Prematurely in Patients With Crouzon
• 17.   Pan CY, Tseng YC, Lan TH, Chang HP. Craniofacial features of cleidocranial dysplasia. Journal of Dental Sciences. 2017 Dec;12(4): 313–8.
• 18.   Coll G, Sakka L, Botella C, Pham-Dang N, Collet C, Zerah M, et al. Pattern of Closure of Skull Base Synchondroses in Crouzon Syndrome.
• 19.   Coll G, Lemaire JJ, Di Rocco F, Barthélémy I, Garcier JM, De Schlichting E, et al. Human Foramen Magnum Area and Posterior Cranial
• 20.   Rijken BFM, Lequin MH, de Rooi JJ, van Veelen MLC, Mathijssen IMJ. Foramen Magnum Size and Involvement of Its Intraoccipital
• 21.   Kanchan T, Krishan K. Evaluation of sphenooccipital synchondrosis: A review of literature and considerations from forensic anthropologic point of view. J Forensic Dent Sci. 2013;5(2):72.
• 22.   Yang JH, Cha BK, Choi DS, Park JH, Jang I. Time and pattern of the fusion of the sphenooccipital synchondrosis in patients with skeletal Class I and Class III malocclusion. The Angle Orthodontist. 2019 May 1;89(3):470–9.
• 23.   Vale F, Francisco I, Lucas A, Roseiro A, Caramelo F, Sobral A. Timing of SphenoOccipital Synchondrosis Ossification in Children and Adolescents with Cleft Lip and Palate: A Retrospective Case-Control Study. IJERPH. 2020 Nov 29;17(23):8889.
• 24.   Coben SE. The spheno-occipital synchondrosis: The missing link between the profession’s concept of craniofacial growth and
• 25.   Leonardi R, Cutrera A, Barbato E. Rapid Maxillary Expansion Affects the Sphenooccipital Synchondrosis in Youngsters: A Study with Low-Dose Computed Tomography. The Angle Orthodontist. 2010 Jan;80(1):106–10.
• 26.   Silvestrini-Biavati A, Migliorati M, Demarziani E, Tecco S, Silvestrini-Biavati F, Polimeni A, et al. Do changes in spheno-occipital
• 27.   Bassed RB, Briggs C, Drummer OH. Analysis of time of closure of the spheno-occipital synchondrosis using computed tomography.
• 28.   Al-Gumaei WS, Al-Attab R, Al-Tayar B, Al-hadad SA, Alyafrusee ES, Al-mashraqi AA, et al. Comparison of spheno-occipital
• 29.   Al-Gumaei WS, Long H, Al-Attab R, Elayah SA, Alhammadi MS, Almagrami I, et al. Comparison of three-dimensional maxillary growth across spheno-occipital synchondrosis maturation stages. BMC Oral Health. 2023 Feb 14;23(1):100.
• 30.   Tashayyodi N, Kajan ZD, Ostovarrad F, Khosravifard N. Relationship of the Fusion Stage of Spheno-Occipital Synchondrosis with
• 31.   Alam MK, Nagarajappa AK, Alfawzan AA, Akhter F, Alswairki HJ, Issrani R, et al. The Spheno-Occipital Synchondrosis and Morphometry of Sella Turcica Association with Different Phenotype Factors Related to Ectopic Eye Tooth/Teeth. Applied Sciences.

Data Sharing Statement

Funding