Confined placental mosaicism for any chromosome (but particularly for trisomy 7, 11, 14, or 15) raises the additional concern that the fetal diploidy may have actually arisen by trisomy rescue. This term refers to the loss of an extra chromosome postzygotically, an event that presumably allows fetal viability. If the fetus has retained two copies of a chromosome from the same parent, however, the result is uniparental disomy (see Chapter 5). Because some genes on the chromosome mentioned are imprinted, uniparental disomy must be excluded; two maternal copies of chromosome 15, for example, cause Prader-Willi syndrome, and two paternal copies are associated with Angelman syndrome (see Chapter 5).
CMA can detect some, but not all, cases of mosaicism. Because CMA uses pooled DNA from tissues or cultured cells and does not examine individual cells the way karyotyping does, it is less sensitive for the detection of mosaicism. Mosaicism in which 10% of the cells are aneuploid is difficult to detect as a copy number change by CMA, whereas 10% mosaicism will be detected with greater than 99% probability when 50 cells are examined by karyotype, as is typically done for the assessment of possible mosaicism. CMA is even less sensitive for detecting mosaicism for a copy number variation of only a segment of a chromosome unless it constitutes more than 20% to 25% of the cells under study.
Confirmation and interpretation of apparent mosaicism are among the most difficult challenges in genetic counseling for prenatal diagnosis because, at present, clinical outcome information on the numerous possible types and extents of mosaicism is limited. Further studies (e.g., amniocentesis that follows CVS, cordocentesis that follows amniocentesis) as well as the medical literature may provide some guidance, but the interpretation sometimes still remains uncertain. Ultrasonographic scanning may provide some reassurance if normal growth is observed and if no congenital anomalies can be demonstrated.
Parents should be counseled in advance of the possibility that mosaicism may be found and that the interpretation of mosaicism may be uncertain. After birth, an effort should be made to verify any abnormal chromosome findings suspected on the basis of prenatal diagnosis. In the case of termination, verification should be sought by analysis of fetal tissues. Confirmation of mosaicism, or lack thereof, may prove helpful with respect to medical management as well as for genetic counseling of the specific couple and other family members.
If couples are to have an opportunity to consider termination of a pregnancy when an abnormality is found in the fetus, they should be provided with the information at the earliest possible time. Because prenatal diagnosis is always a race against time, the rate of culture failure can be a concern; fortunately, this rate is low. When a CVS culture fails to grow, there is time to repeat the chromosome study with amniocentesis. If an amniotic fluid cell culture fails, either repeated amniocentesis or cordocentesis can be offered, depending on fetal age.