X-linked hypophosphatemic rickets and craniosynostosis

• Published in: The Journal of craniofacial surgery Vol. 20; no. 2; p. 439
• Main Author: Murthy, Ananth S
• Format: Journal Article
• Language: English
• Published: United States 01.03.2009
• Subjects: Bone Remodeling - genetics; Bone Transplantation - methods; Calcification, Physiologic - genetics; Cranial Sutures - surgery; Craniosynostoses - etiology; Craniosynostoses - surgery; Craniotomy - methods; Exons - genetics; Familial Hypophosphatemic Rickets - complications; Familial Hypophosphatemic Rickets - genetics; Fibroblast Growth Factors - genetics; Follow-Up Studies; Genetic Diseases, X-Linked; Homeostasis - physiology; Humans; Infant, Newborn; Intracranial Hypertension - etiology; Male; Mutation - genetics; Occipital Bone - surgery; Parietal Bone - surgery; PHEX Phosphate Regulating Neutral Endopeptidase - genetics; Tryptophan - genetics
• ISSN: 1536-3732
• DOI: 10.1097/SCS.0b013e31819b9868

Bone mineralization is possible via complex interactions among fibroblast growth factor 23 (FGF23), phosphate-regulating gene with homologies to endopeptidases on the X-chromosome (PHEX), and matrix extracellular phosphoglycoprotein. A loss-of-function mutation in PHEX disrupts this interaction leading to hypophosphatemic rickets. X-linked hypophosphatemic (XLH) rickets is the most common form of metabolic rickets, and there have been reports linking XLH rickets to craniosynostosis. A clinical report of a patient with XLH rickets and craniosynostosis is presented with a review of literature. A review of physiology of bone mineralization reveals that, at high levels, there is cross-binding of FGF23 with FGF receptors 2 and 3 at the cranial sutures. This may be the reason for the common association of craniosynostosis and XLH rickets. There are complex interactions of proteins required for mineralization, proteins inhibiting mineralization, bone remodeling, and bone-renal phosphate homeostasis. Clarification of this pathway and reproducibility in a mouse model may pave the way for medical prevention of craniosynostosis in rickets.