Citation

Tinkle BT, Wenstrup RJ. Am. J. Med. Genet. C Semin. Med. Genet. 2005; 139(1): 38-54.

Copyright

(Copyright © 2005, John Wiley and Sons)

DOI

10.1002/ajmg.c.30073

PMID

unavailable

Abstract

The purpose of this report is to provide a review of both childhood fracture epidemiology and known heritable causes for fracture predisposition to the Medical Geneticist, who is frequently consulted to assess children with multiple or unexplained fractures for a physiologic etiology. A detailed knowledge of the clinical and laboratory evaluation for osteogenesis imperfecta (OI) and other single-gene disorders is obviously essential to complete a useful evaluation of such children. The experienced clinician will immediately recognize that single gene disorders represent only a small fraction of these patients. In infants, non-accidental trauma (NAT) unfortunately is the likely explanation for the fracture pattern, but in some infants, and certainly in older children with recurrent fractures, no medical explanations can be found. Recent studies in which bone mineral density (BMD) has been associated with genetic variation at a number of candidate genes are promising but these studies are too premature yet to be used clinically. Nonetheless, we do expect that in the future whole-genome approaches in conjunction with key clinical and epidemiological variables may be combined through an informatics approach to create better predictors of fracture susceptibility for these populations of patients. © 2005 Wiley-Liss, Inc.