The Principles of Clinical Cytogenetics - Extra Materials - Springer

310 Linda Marie Randolph
DNA marker analysis. Virtually all mosaic trisomy 16 is thought to arise from trisomic zygote
rescue of error of maternal origin (273). Nonmosaic trisomy 16 has not been observed in a liveborn
child, although it was documented in a third-trimester fetus at 32 weeks’ gestation. That fetus was
stillborn with a birth weight of 783 g, indicating severe IUGR, and the diagnosis was confirmed in
skin chromosomes (274).
Mosaic trisomy 16 is commonly reported in CVS cultures (275,276) and has been reported to
result in the birth of liveborn infants with maternal uniparental disomy or with normal biparental
inheritance of the normal cell line. When CVS detection of mosaic trisomy 16 occurred, in 1 series of
continued pregnancies, 13/63 resulted in fetal death, with 3 of those occurring after 37 weeks’ gestation.
One baby was stillborn. Preterm delivery occurred in 11 cases, often associated with fetal or
maternal complications. Among the 50 liveborns, IUGR was seen in 27, or more than half. Birth
defects or fetal abnormalities were seen in 13, or 18%, of cases; multiple abnormalities were seen in
6, and the abnormalities were isolated to a single organ in 7. Of the continuing pregnancies, only 17
of 60, or 28%, appeared to be full-term, normal pregnancy outcomes (276).
Finding mosaic trisomy 16 at amniocentesis appears to be associated with an elevated maternal
serum AFP (MSAFP; see above). Hsu et al. (277) reported on a series of 11 cases diagnosed via
amniocentesis ascertained after an elevated MSAFP. In their series, 9 of the 11 pregnancies affected
with mosaic trisomy 16 were referred for this reason or because of elevated maternal serum human
chorionic gonadotropins.
In another series of 29 amniocentesis-diagnosed cases of trisomy 16 mosaicism not referred because
of abnormal CVS results, the indication was elevated MSAFP in 12; in only 3 was the indication abnormal
ultrasound findings. Preterm delivery was seen in 12 of the 19 pregnancies, and IUGR was seen in
13 of the 19 continuing pregnancies. Multiple abnormalities were seen in 18 of the 29 cases, or 62%,
and isolated abnormalities were seen in 2 other babies. Only four appeared to have a totally normal
outcome (276). It is important to study skin fibroblasts, as often the trisomic cell line does not appear in
lymphocytes. Placental tissue should also undergo chromosome or FISH analysis (276).
Is there is a phenotype associated with trisomy 16 mosaicism? Some abnormalities have occurred
more than once in affected fetuses and newborns (viz. VSD, complex heart disease, hypospadias,
imperforate anus, inguinal hernia, club foot, and IUGR). The combination of an elevated maternal
serum hCG or AFP, plus IUGR and one or more of the above-listed structural abnormalities could
raise the clinical suspicion of mosaic trisomy 16 (276).
Other Mosaic Trisomies and Monosomies
Trisomy 22 mosaicism was reported in a collection of 11 cases (30). Of these, four continued and
five terminated. Four of eight reported cases showed a normal outcome, and in the others, one fetal
demise, one neonatal death with IUGR, one liveborn with IUGR, and one abortus with multiple
congenital abnormalities were seen.
In a study of chromosome mosaicism of chromosomes other than 13, 18, 20, and 21, 1 to 25 cases
each of mosaic trisomies 2–9, 11, 12, 14, 15, 16, 17, 19, and 22 were reported in 1 series (278). The
outcomes were stratified by very high, high, moderately high, moderate, low, and undetermined.
Most abnormalities were detectable by ultrasound. The authors also stressed the importance of obtaining
fibroblasts and placental tissues. See Table 18 for more information on these mosaic trisomies.
Hsu reported on 13 cases of autosomal monosomy mosaicism that had been prenatally diagnosed
(30). These included five cases of monosomy 21, three of monosomy 22, two of monosomy 17, and
one case each of monosomies 9, 19, and 20. Of seven cases with phenotypic information and four
cases with confirmatory cytogenetic studies, only one case with monosomy 22 was reported to have
multiple congenital abnormalities, including congenital heart disease. Another case of monosomy 21
was confirmed but reported to be phenotypically normal. If autosomal mosaic monosomy is detected,
particularly of chromosomes 21 or 22, further workup, such as PUBS and ultrasound examination, is
indicated.