Case Report: Neonatal COL1A1-related osteogenesis imperfecta recognized after multiple fractures in an infant admitted for jaundice
- 1Department of Neonatology, Wuhan Children's Hospital (Wuhan Maternal and Child Health Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China
- 2Department of Radiology, Wuhan Children's Hospital (Wuhan Maternal and Child Health Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China
Abstract
BackgroundOsteogenesis 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 presentationWe 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.ConclusionThis 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.
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BibTeX
@article{gui2026case,
title = {{Case Report: Neonatal COL1A1-related osteogenesis imperfecta recognized after multiple fractures in an infant admitted for jaundice}},
author = {Shuxia Gui and Jingxian Gong and Xiaoqin Pi and Jing Zhou and Lingkong Zeng and Wenhao Yuan},
journal = {Frontiers in Pediatrics},
year = {2026},
month = oct,
doi = {10.3389/fped.2026.1962700},
url = {https://doi.org/10.3389/fped.2026.1962700},
note = {CC BY},
}
RIS
TY - JOUR
TI - Case Report: Neonatal COL1A1-related osteogenesis imperfecta recognized after multiple fractures in an infant admitted for jaundice
AU - Shuxia Gui
AU - Jingxian Gong
AU - Xiaoqin Pi
AU - Jing Zhou
AU - Lingkong Zeng
AU - Wenhao Yuan
PY - 2026
DA - 2026/10/30
JO - Frontiers in Pediatrics
DO - 10.3389/fped.2026.1962700
UR - https://doi.org/10.3389/fped.2026.1962700
AB - BackgroundOsteogenesis 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 presentationWe 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.ConclusionThis 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.
SN - 2296-2360
ER -