Related Experiment Video
Updated: Mar 30, 2026
Scanning Skeletal Remains for Bone Mineral Density in Forensic Contexts
Published on: January 29, 2018
What every clinical geneticist should know about testing for osteogenesis imperfecta in suspected child abuse cases
Insights
Diagnosing mild osteogenesis imperfecta (OI) in infants with fractures is crucial to differentiate from non-accidental injury (NAI). Genetic testing for COL1A1, COL1A2, and IFITM5 is recommended when NAI is suspected but OI is not clinically apparent.
Area of Science:
- Pediatrics
- Genetics
- Orthopedics
Background:
- Non-accidental injury (NAI) is a significant concern in pediatric medicine, often presenting with unexplained fractures.
- Mild forms of osteogenesis imperfecta (OI) can mimic NAI, posing diagnostic challenges due to the absence of typical clinical features in infants.
- Differentiating between NAI and genetic bone fragility is critical for appropriate patient management.
Purpose of the Study:
- To review clinical presentations of mild OI and the role of genetic testing in differentiating OI from NAI.
- To summarize molecular testing data for COL1A1 and COL1A2 in cases with suspected NAI.
- To provide recommendations for genetic testing strategies in the NAI versus OI differential diagnosis.
Main Methods:
- Review of clinical presentations of mild OI types I and IV.
- Analysis of molecular testing data from the Collagen Diagnostic Laboratory (CDL) between 2008 and 2014 for COL1A1 and COL1A2 sequencing.
- Evaluation of genetic testing recommendations in the context of suspected NAI.
Main Results:
- Diagnostic clinical features of OI may be absent or subtle in infants, complicating diagnosis.
- Molecular testing data from CDL cases with NAI noted on requests were summarized.
- Recommendations for simultaneous DNA sequencing of COL1A1, COL1A2, and IFITM5, along with duplication/deletion testing, are proposed.
Conclusions:
- Genetic testing is essential when mild OI is suspected in infants presenting with fractures and NAI is a consideration.
- Simultaneous sequencing of key genes and deletion/duplication analysis is recommended.
- Parental segregation studies are advised for variants of uncertain significance (VUS).
Abstract:
Non-accidental injury (NAI) is a major medical concern in the United States. One of the challenges in evaluation of children with unexplained fractures is that genetic forms of bone fragility are one of the differential diagnoses. Infants who present with fractures with mild forms of osteogenesis imperfecta (OI) (OI type I or OI type IV), the most common genetic form of bone disease leading to fractures might be missed if clinical evaluation alone is used to make the diagnosis. Diagnostic clinical features (blue sclera, dentinogenesis imperfecta, Wormian bones on X-rays or positive family history) may not be present or apparent at the age of evaluation. The evaluating clinician faces the decision about whether genetic testing is necessary in certain NAI cases. In this review, we outline clinical presentations of mild OI and review the history of genetic testing for OI in the NAI versus OI setting. We summarize our data of molecular testing in the Collagen Diagnostic Laboratory (CDL) from 2008 to 2014 where NAI was noted on the request for DNA sequencing of COL1A1 and COL1A2. We provide recommendations for molecular testing in the NAI versus OI setting. First, DNA sequencing of COL1A1, COL1A2, and IFITM5 simultaneously and duplication/deletion testing is recommended. If a causative variant is not identified, in the absence of a pathologic clinical phenotype, no additional gene testing is indicated. If a VUS is found, parental segregation studies are recommended.
More Related Videos
07:35Creating Rigidly Stabilized Fractures for Assessing Intramembranous Ossification, Distraction Osteogenesis, or Healing of Critical Sized Defects
Published on: April 11, 2012
09:02Cortical Bone Assessment Using Ultrasonic Guided Waves: A Reproducibility Study in a Healthy Population
Published on: January 31, 2025
Related Concept Videos
01:29Bone Disorders
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
01:27Fractures: Bone Repair
Minor fractures with no bone displacement are treated by immobilizing the fractured bone using a cast or splint. However, in the case of fractures with displaced bones, the broken bones are repositioned before immobilization to ensure successful healing without deformation and loss of function. The realignment of fractured bone ends is performed through a process called reduction. If the...