What every clinical geneticist should know about testing for osteogenesis imperfecta in suspected child abuse cases
- PMID: 26566591
- DOI: 10.1002/ajmg.c.31459
What every clinical geneticist should know about testing for osteogenesis imperfecta in suspected child abuse cases
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.
Keywords: biochemical testing osteogenesis imperfecta; child abuse; molecular testing osteogenesis imperfecta; osteogenesis imperfecta; recurrent fracture.
© 2015 Wiley Periodicals, Inc.
Similar articles
-
Clinical perspectives on osteogenesis imperfecta versus non-accidental injury.Am J Med Genet C Semin Med Genet. 2015 Dec;169(4):302-6. doi: 10.1002/ajmg.c.31463. Epub 2015 Oct 22. Am J Med Genet C Semin Med Genet. 2015. PMID: 26492946 Review.
-
[Child abuse and osteogenesis imperfecta. How do we distinguish?].Ugeskr Laeger. 2000 Mar 13;162(11):1528-33. Ugeskr Laeger. 2000. PMID: 10868105 Review. Danish.
-
COL1A1 and COL1A2 sequencing results in cohort of patients undergoing evaluation for potential child abuse.Am J Med Genet A. 2016 Jul;170(7):1858-62. doi: 10.1002/ajmg.a.37664. Epub 2016 Apr 19. Am J Med Genet A. 2016. PMID: 27090748
-
Osteogenesis imperfecta: the distinction from child abuse and the recognition of a variant form.Am J Med Genet. 1993 Jan 15;45(2):187-92. doi: 10.1002/ajmg.1320450208. Am J Med Genet. 1993. PMID: 8456801 Review.
-
Molecular diagnosis in children with fractures but no extraskeletal signs of osteogenesis imperfecta.Osteoporos Int. 2017 Jul;28(7):2095-2101. doi: 10.1007/s00198-017-4031-2. Epub 2017 Apr 4. Osteoporos Int. 2017. PMID: 28378289
Cited by
-
"Mimics" of Injuries from Child Abuse: Case Series and Review of the Literature.Children (Basel). 2024 Sep 9;11(9):1103. doi: 10.3390/children11091103. Children (Basel). 2024. PMID: 39334635 Free PMC article.
-
Reviewing hereditary connective tissue disorders: Proposals of harmonic medicolegal assessments.Int J Legal Med. 2024 Nov;138(6):2507-2522. doi: 10.1007/s00414-024-03290-4. Epub 2024 Jul 15. Int J Legal Med. 2024. PMID: 39008115 Free PMC article. Review.
-
NGS analysis of collagen type I genes in Polish patients with Osteogenesis imperfecta: a nationwide multicenter study.Front Endocrinol (Lausanne). 2023 Sep 22;14:1149982. doi: 10.3389/fendo.2023.1149982. eCollection 2023. Front Endocrinol (Lausanne). 2023. PMID: 37810882 Free PMC article.
-
Genotype-phenotype relationship and comparison between eastern and western patients with osteogenesis imperfecta.J Endocrinol Invest. 2024 Jan;47(1):67-77. doi: 10.1007/s40618-023-02123-2. Epub 2023 Jun 4. J Endocrinol Invest. 2024. PMID: 37270749 Free PMC article.
-
Metaphyseal and posterior rib fractures in osteogenesis imperfecta: Case report and review of the literature.Bone Rep. 2022 Feb 8;16:101171. doi: 10.1016/j.bonr.2022.101171. eCollection 2022 Jun. Bone Rep. 2022. PMID: 35242891 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous
