Case Report: Neonatal COL1A1-related osteogenesis imperfecta recognized after multiple fractures in an infant admitted for jaundice

Background Osteogenesis imperfecta (OI) is a rare inherited skeletal fragility disorder characterized by impaired bone strength and increased susceptibility to fractures. Most genetically confirmed cases are associated with pathogenic variants affecting type I collagen, particularly COL1A1 and COL1A2. Severe neonatal OI may present with multiple fractures, skeletal deformities, and respiratory complications; however, early diagnosis remains challenging because classical clinical manifestations may be absent during the neonatal period. Case presentation We report a term male neonate with COL1A1-related osteogenesis imperfecta associated with an apparently de novo pathogenic variant in COL1A1. The infant was born at 38 + 4 weeks of gestation by elective cesarean delivery with a birth weight of 3040 g. He was initially admitted to the neonatal intensive care unit because of progressive jaundice on day 3 of life. No obvious skeletal abnormalities, limb deformities, or apparent blue sclerae were identified during the initial examination. On day 5 after birth, swelling and reduced spontaneous movement of the right lower extremity were observed. Radiological evaluation identified right femoral, radial, clavicular, and multiple rib fractures. The timing of fracture occurrence remained uncertain. Laboratory investigations showed normal serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone, and vitamin D levels, making a major mineral metabolism disturbance less likely. Subsequent trio whole-exome sequencing identified a heterozygous apparently de novo missense variant in COL1A1 (NM_000088.4:c.581G > A, p.Gly194Asp), located within the triple-helical domain of type I collagen. The laboratory classified the variant as pathogenic according to the American College of Medical Genetics and Genomics/Association for Molecular Pathology criteria. The patient received multidisciplinary management, including fracture stabilization, protective nursing strategies, orthopedic intervention, and genetic counseling. Early follow-up demonstrated progressive fracture healing with callus formation; clinical severity classification requires longer follow-up. Conclusion This case highlights that neonatal OI may initially present with nonspecific clinical manifestations and without classical phenotypic features. Unexplained fractures in neonates should prompt consideration of inherited skeletal fragility disorders. Early molecular diagnosis is essential for confirmation of diagnosis, genetic counseling, prevention of secondary injury, and individualized multidisciplinary management.