Prolyl 3-Hydroxylase 1 (P3H1) Deficient Osteogenesis Imperfecta with Vascular Malformations: A rare disorder with atypical features

Abstract Osteogenesis imperfecta (OI) is a genetic disorder characterized by skeletal fragility with increased susceptibility to fractures, alongside various extra-skeletal manifestations. It has a wide spectrum of clinical presentations and varying degree of severity. Over the years, the classification of OI has expanded, and new pathogenic variants are being identified in genes involved in the regulation of collagen synthesis. We describe a case of a 4-year-old boy who first presented with right eye swelling, redness, proptosis, and limitation in extraocular movements. Further investigation revealed presence of large left sphenoid vascular malformation (VM). He was treated with repeated embolization and oral propranolol. A year later, he suffered a pathological fracture of the left proximal femur. This was followed by recurrent fractures over a period of five years. Radiographs and magnetic resonance imaging (MRI) showed multiple osteolytic lesions in his skull and extremities, and he had low bone mineral density (BMD). Genetic testing identified biallelic variants in the P3H1 gene. Intravenous zoledronate therapy was commenced and improvement in BMD and remodeling of bones were seen after four doses. There was concurrent development of a right sphenoid VM and widespread intraosseous slow-flow VMs seen on serial MRI. He was treated with oral sirolimus for 5 years and 5 months duration. There was eventual resolution of sphenoid VMs, while intraosseous VMs remained stable. This is a case of P3H1 deficient OI with atypical clinical features, and the presence of vascular malformations that may or may not be related to underlying collagen defects but may have implications on his treatment and surveillance.