Sometimes, women who do not have osteogenesis imperfecta (OI) become concerned about it during pregnancy. Two situations typically give rise to this concern.
In both situations, the woman and her partner should seek advice from a geneticist.
Osteogenesis imperfecta is the result of a mutation in one of the two genes that carry instructions for making type 1 collagen -- the major protein in bone and skin. The mutation may result in either a change in the structure of type 1collagen molecules or in the number of collagen molecules made. Either of these changes results in weak bones that fracture easily and other connective tissue symptoms. Results of studies in recent years show that the great majority of people with OI, even those who are the only affected person in a family, have dominantly inherited forms of the disorder. For more detailed information about the genetics of OI inheritance, see the OI Foundation fact sheet, OI Issues: Genetics.
When the woman’s partner has OI
A person with OI has a 50 percent chance of passing on the disorder to each child. The child will have the same OI-causing mutation as the parent, although the child’s symptoms may be milder or more severe than the parent’s symptoms. It is possible that the child of a person with OI will have a spontaneous genetic mutation resulting in a different type of OI, but the chances of this happening are no greater for a parent with OI than they are for the general population. Some individuals with very mild OI have been known to have a child with more severe symptoms. In these cases it is believed that the parent is a mildly affected mosaic for OI. Mosaicism means that the individual carries a mutation for OI in only some of his or her cells. This can cause very mild symptoms of OI, or none at all in the carrier. Excluding OI, the risk of other congenital disorders in pregnancies in which one parent has OI is the same as that of the general population.
Preimplantation genetic testing or preimplantation genetic diagnosis is a new procedure. It involves in vitro fertilization plus the added step of “embryo analysis.” After a couple has gone through the initial stages for in vitro fertilization and embryos have been formed, a single cell is removed from the dividing cells at the 8-cell stage and is tested for a single genetic condition, in this case, OI. If the embryo does not show any signs of OI, it is then implanted in the mother to continue normal development. At this time there is no known adverse effect on the fetus to having one cell removed at this stage. To be a candidate for this procedure, the parent’s exact genetic mutation must be identified, usually through a collagen biopsy or DNA analysis and a mutation-specific test developed. This procedure cannot remove the OI gene (or the gene for any other condition), but only embryos without the mutation are implanted.
Undergoing prenatal diagnosis does not obligate parents to elect pregnancy termination, and the information may be useful in managing pregnancy and delivery. There are three techniques for prenatal diagnosis of OI in a fetus; ultrasound, chorionic villus sampling (CVS) and amniocentesis. None of these techniques can detect OI in 100 percent of the cases in which it occurs. Individualized assessment by a genetic counselor and/or geneticist is necessary to determine which techniques are most useful for a particular pregnancy.
It is also recommended that couples discuss their genetic history with the obstetrician. Parents may want to make arrangements, prior to the due date, to have a cord blood saved for DNA analysis. It can be helpful for families at risk for OI Type I or Type IV to have the question of OI inheritance answered as soon as possible.
When prenatal testing suggests
Sometimes, through routine ultrasound, OI is suspected in the fetus of an unaffected mother. This often leads to additional ultrasound tests at higher levels and/or referral to a center for high-risk pregnancies. In the majority of cases, there is no previous history of OI. In a few instances, the ultrasound may have been ordered because of a previously affected pregnancy. In either situation, the finding presents certain medical and ethical questions to be addressed by the couple and their medical team. The questions include accuracy of the diagnosis, severity of the disorder, and prognosis for survival and development. The answers will help direct the remainder of the prenatal care and mode of delivery. It should be noted that it can be difficult to tell from an ultrasound whether the fetus has OI Type II or Type III.
Chorionic villus sampling (CVS) and amniocentesis analyze cells obtained from the fetus for collagen defects and/or a genetic mutation that causes OI. CVS looks at placental cells, while amniocentesis examines fetal cells (amniocytes) shed into the amniotic fluid. Both of these procedures carry a risk of miscarriage (about 1 in 200 for amniocentesis and about 1 percent for CVS). These prenatal tests are useful if the parent who has OI already has the results of his or her own collagen or DNA tests.
When faced with these findings, couples are typically advised that Type II OI is most often lethal at birth or in early infancy and that Type III is associated with significant disability and at times early mortality. Because it is sometimes difficult to distinguish Types II and III OI prenatally, parents have sometimes been given a lethal prognosis for a fetus who actually had Type III OI.
Managing the Pregnancy
According to a recent study (Cubert et al), cesarean delivery did not decrease fracture rates at birth in infants with nonlethal forms of OI, nor did it prolong survival for those with lethal forms. This study also found that most cesarean deliveries were done for the usual obstetric indications and not specifically because OI was detected in the fetus.
Information is available from the Osteogenesis Imperfecta Foundation regarding caring for an infant who has OI.
This fact sheet was prepared by the Osteogenesis Imperfecta Foundation with the assistance of Dr. Deborah Krakow, Department of Genetics, Cedars-Sinai Medical Center, Los Angeles, California. Dr. Krakow is a member of the OI Foundation’s Medical Advisory Council.
This information is brought to you by the
National Institutes of Health
The National Resource Center is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases with contributions from the National Institute of Child Health and Human Development, National Institute of Dental and Craniofacial Research, National Institute of Environmental Health Sciences, NIH Office of Research on Women's Health, Office of Women's Health, PHS, and the National Institute on Aging. The Resource Center is operated by the National Osteoporosis Foundation, in collaboration with the Paget Foundation and the Osteogenesis Imperfecta Foundation.