Secondary Craniosynostosis in Metabolic and Hematologic Disorders

Introduction: Secondary craniosynostosis can occur in patients with metabolic and hematologic disorders. However, current studies have been limited due to the rarity of these pathologies. The current study uses a large nationwide multi-institution database to evaluate patient demographics, suture patterns, and associated comorbidities. Methods: A retrospective analysis of the TriNetX database was performed for patients diagnosed with craniosynostosis and X-linked hypophosphatemia (XLH), vitamin D-resistant rickets (VDRR), pseudohypoparathyroidism, glycosaminoglycan disorder, osteopetrosis, sickle cell, thalassemia, and polycythemia vera. Demographics, suture patterns, and craniofacial, orthopedic, and systemic congenital malformations were evaluated. Results: About 1,902 patients with secondary craniosynostosis with metabolic or hematologic disorders were identified. Two hundred sixty six patients with XLH, 236 with VDRR, 136 with pseudohypoparathyroidism, 283 with hyperthyroidism, 103 with glycosaminoglycan disorder, 27 with osteopetrosis, 509 with sickle cell, 302 with thalassemia, and 40 with polycythemia vera. The most common suture involvement was sagittal in XLH (68.18%), VDRR (55.56%), hyperthyroidism (52.94%), thalassemia (43.18%), and sickle cell (36.78%). Multiple suture involvement also commonly occurred, especially in osteopetrosis (66.67%), pseudohypoparathyroidism (40.00%), and glycosaminoglycan disorder (30.00%). Chiari malformations and hydrocephalus were common in XLD, VDRR, and osteopetrosis. Orthopedic comorbidities occurred frequently in osteopetrosis, glycosaminoglycan disorder, VDRR, and XLH. Congenital cardiac malformation was common in all groups. Elevated rates of all congenital systemic malformations were seen in XLH, VDRR, and pseudohypoparathyroidism. Conclusions: Metabolic and hematologic disorders with secondary craniosynostosis are associated with sagittal and multi-suture closure patterns. Multiple groups showed increased rates of other craniofacial, orthopedic, and congenital systemic malformations.