Skip to main content
NCBI home page
Journal of Medical Genetics logoLink to Journal of Medical Genetics
. 2002 Jun;39(6):382–386. doi: 10.1136/jmg.39.6.382

Testing for osteogenesis imperfecta in cases of suspected non-accidental injury

A Marlowe 1, M Pepin 1, P Byers 1
PMCID: PMC1735162  PMID: 12070242

Abstract

To evaluate if laboratory testing for osteogenesis imperfecta (OI) identifies children unrecognised by clinical examination in instances where non-accidental injury (NAI) is suspected as the likely cause of fracture, we carried out a retrospective review of available medical records and biochemical test results from 262 patients. Cultured fibroblasts were received for biochemical testing for OI from children in whom the diagnosis of NAI was suspected. Eleven of the samples had alterations in the amount or structure of type I collagen synthesised, consistent with the diagnosis of OI, and in 11 others we could not exclude OI. Referring physicians correctly identified children with OI in six of the 11 instances established by biochemical studies, did not identify OI by clinical examination in three, and there was inadequate clinical information to know in two others. Biochemical testing was inconclusive in 11 infants in whom the diagnosis of OI could not be excluded, none of whom were thought to be affected by the referring clinicians. Four children believed to have OI by clinical examination had normal biochemical studies, a false positive clinical diagnosis attributed, in large part, to the use of scleral hue (a feature that is age dependent) as a major diagnostic criterion.

Given the inability to identify all children with OI by clinical examination in situations of suspected NAI, laboratory testing for OI (and other genetic predispositions for fractures) is a valuable adjunct in discerning the basis for fractures and may identify a small group of children with previously undiagnosed OI.

Full Text

The Full Text of this article is available as a PDF (110.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ablin D. S., Greenspan A., Reinhart M., Grix A. Differentiation of child abuse from osteogenesis imperfecta. AJR Am J Roentgenol. 1990 May;154(5):1035–1046. doi: 10.2214/ajr.154.5.2108539. [DOI] [PubMed] [Google Scholar]
  2. Adams P. C., Strand R. D., Bresnan M. J., Lucky A. W. Kinky hair syndrome: serial study of radiological findings with emphasis on the similarity to the battered child syndrome. Radiology. 1974 Aug;112(2):401–407. doi: 10.1148/112.2.401. [DOI] [PubMed] [Google Scholar]
  3. Amir J., Katz K., Grunebaum M., Yosipovich Z., Wielunsky E., Reisner S. H. Fractures in premature infants. J Pediatr Orthop. 1988 Jan-Feb;8(1):41–44. doi: 10.1097/01241398-198801000-00010. [DOI] [PubMed] [Google Scholar]
  4. Andersen P. E., Jr, Hauge M. Osteogenesis imperfecta: a genetic, radiological, and epidemiological study. Clin Genet. 1989 Oct;36(4):250–255. doi: 10.1111/j.1399-0004.1989.tb03198.x. [DOI] [PubMed] [Google Scholar]
  5. Barsh G. S., Roush C. L., Bonadio J., Byers P. H., Gelinas R. E. Intron-mediated recombination may cause a deletion in an alpha 1 type I collagen chain in a lethal form of osteogenesis imperfecta. Proc Natl Acad Sci U S A. 1985 May;82(9):2870–2874. doi: 10.1073/pnas.82.9.2870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bonadio J., Byers P. H. Subtle structural alterations in the chains of type I procollagen produce osteogenesis imperfecta type II. Nature. 1985 Jul 25;316(6026):363–366. doi: 10.1038/316363a0. [DOI] [PubMed] [Google Scholar]
  7. Bonadio J., Holbrook K. A., Gelinas R. E., Jacob J., Byers P. H. Altered triple helical structure of type I procollagen in lethal perinatal osteogenesis imperfecta. J Biol Chem. 1985 Feb 10;260(3):1734–1742. [PubMed] [Google Scholar]
  8. Chu M. L., Williams C. J., Pepe G., Hirsch J. L., Prockop D. J., Ramirez F. Internal deletion in a collagen gene in a perinatal lethal form of osteogenesis imperfecta. Nature. 1983 Jul 7;304(5921):78–80. doi: 10.1038/304078a0. [DOI] [PubMed] [Google Scholar]
  9. Cohn D. H., Byers P. H., Steinmann B., Gelinas R. E. Lethal osteogenesis imperfecta resulting from a single nucleotide change in one human pro alpha 1(I) collagen allele. Proc Natl Acad Sci U S A. 1986 Aug;83(16):6045–6047. doi: 10.1073/pnas.83.16.6045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dahlenburg S. L., Bishop N. J., Lucas A. Are preterm infants at risk for subsequent fractures? Arch Dis Child. 1989 Oct;64(10 Spec No):1384–1385. doi: 10.1136/adc.64.10_spec_no.1384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gahagan S., Rimsza M. E. Child abuse or osteogenesis imperfecta: how can we tell? Pediatrics. 1991 Nov;88(5):987–992. [PubMed] [Google Scholar]
  12. Kafil-Hussain N. A., Monavari A., Bowell R., Thornton P., Naughten E., O'Keefe M. Ocular findings in glutaric aciduria type 1. J Pediatr Ophthalmol Strabismus. 2000 Sep-Oct;37(5):289–293. [PubMed] [Google Scholar]
  13. Körkkö J., Ala-Kokko L., De Paepe A., Nuytinck L., Earley J., Prockop D. J. Analysis of the COL1A1 and COL1A2 genes by PCR amplification and scanning by conformation-sensitive gel electrophoresis identifies only COL1A1 mutations in 15 patients with osteogenesis imperfecta type I: identification of common sequences of null-allele mutations. Am J Hum Genet. 1998 Jan;62(1):98–110. doi: 10.1086/301689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Merten D. F., Carpenter B. L. Radiologic imaging of inflicted injury in the child abuse syndrome. Pediatr Clin North Am. 1990 Aug;37(4):815–837. doi: 10.1016/s0031-3955(16)36938-3. [DOI] [PubMed] [Google Scholar]
  15. Paterson C. R. Vitamin D deficiency rickets simulating child abuse. J Pediatr Orthop. 1981;1(4):423–425. doi: 10.1097/01241398-198112000-00012. [DOI] [PubMed] [Google Scholar]
  16. Penttinen R. P., Lichtenstein J. R., Martin G. R., McKusick V. A. Abnormal collagen metabolism in cultured cells in osteogenesis imperfecta. Proc Natl Acad Sci U S A. 1975 Feb;72(2):586–589. doi: 10.1073/pnas.72.2.586. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pihlajaniemi T., Dickson L. A., Pope F. M., Korhonen V. R., Nicholls A., Prockop D. J., Myers J. C. Osteogenesis imperfecta: cloning of a pro-alpha 2(I) collagen gene with a frameshift mutation. J Biol Chem. 1984 Nov 10;259(21):12941–12944. [PubMed] [Google Scholar]
  18. Sillence D. O., Senn A., Danks D. M. Genetic heterogeneity in osteogenesis imperfecta. J Med Genet. 1979 Apr;16(2):101–116. doi: 10.1136/jmg.16.2.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Steiner R. D., Pepin M., Byers P. H. Studies of collagen synthesis and structure in the differentiation of child abuse from osteogenesis imperfecta. J Pediatr. 1996 Apr;128(4):542–547. doi: 10.1016/s0022-3476(96)70367-0. [DOI] [PubMed] [Google Scholar]
  20. Stoll C., Dott B., Roth M. P., Alembik Y. Birth prevalence rates of skeletal dysplasias. Clin Genet. 1989 Feb;35(2):88–92. doi: 10.1111/j.1399-0004.1989.tb02912.x. [DOI] [PubMed] [Google Scholar]
  21. Sullivan P. M., Knutson J. F. Maltreatment and disabilities: a population-based epidemiological study. Child Abuse Negl. 2000 Oct;24(10):1257–1273. doi: 10.1016/s0145-2134(00)00190-3. [DOI] [PubMed] [Google Scholar]
  22. Tosi L. L. Osteogenesis imperfecta. Curr Opin Pediatr. 1997 Feb;9(1):94–99. doi: 10.1097/00008480-199702000-00019. [DOI] [PubMed] [Google Scholar]
  23. Wardinsky T. D., Vizcarrondo F. E., Cruz B. K. The mistaken diagnosis of child abuse: a three-year USAF Medical Center analysis and literature review. Mil Med. 1995 Jan;160(1):15–20. [PubMed] [Google Scholar]
  24. Wenstrup R. J., Willing M. C., Starman B. J., Byers P. H. Distinct biochemical phenotypes predict clinical severity in nonlethal variants of osteogenesis imperfecta. Am J Hum Genet. 1990 May;46(5):975–982. [PMC free article] [PubMed] [Google Scholar]
  25. Westerhausen A. I., Constantinou C. D., Prockop D. J. A sequence polymorphism in the 3'-nontranslated region of the pro alpha 1 chain of type I procollagen. Nucleic Acids Res. 1990 Aug 25;18(16):4968–4968. doi: 10.1093/nar/18.16.4968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Willing M. C., Pruchno C. J., Atkinson M., Byers P. H. Osteogenesis imperfecta type I is commonly due to a COL1A1 null allele of type I collagen. Am J Hum Genet. 1992 Sep;51(3):508–515. [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Medical Genetics are provided here courtesy of BMJ Publishing Group

RESOURCES