Craniosynostosis in Children with X-Linked Hypophosphatemia Treated with Burosumab: Insights from a Single Center Cross-sectional Cohort Screening

Background X-linked hypophosphatemic rickets (XLH) is the most common genetic form of hypophosphatemia, caused by elevated FGF23 and renal phosphate wasting. Cranial anomalies such as craniosynostosis (CS) and Chiari type I malformation (CM-I) are reported in XLH, but prevalence data—especially in the context of burosumab therapy—remain limited. This monocentric study evaluated (a) the prevalence and predictors of CS and CM-I in children with XLH receiving burosumab, and (b) the utility of brain black bone MRI as a nonionizing alternative to computed tomography (CT). Methods Twelve children (8.3 ± 4.6 years; four males) were assessed after a mean burosumab treatment duration of 28 ± 14.6 months. All were asymptomatic or paucisymptomatic for CS. Cranial morphology was evaluated via CT, and MRI was performed in patients with CS; three children without CS underwent MRI with black bone sequences. Results CS with sagittal suture fusion was present in 41.7% of patients, and CM-I in 25%. No patient had a normal cranial index(>80%).CS correlated significantly with male sex(p < 0.01), dolichocephaly(p < 0.001), and CM-I(p < 0.01). black bone sequences MRI successfully visualized sutures in children without CS. Burosumab improved phosphate metabolism and rickets, but showed no association with CS prevalence. Conclusions Sagittal suture fusion and CM-I are common in XLH, with male sex and dolichocephaly identified as strong predictors of CS. These findings underscore the importance of radiological screening in XLH and support MRI with black bone sequences as a promising diagnostic tool.