The Principles of Clinical Cytogenetics - Extra Materials - Springer

Prenatal Cytogenetics 309
somic cells differed also, with better outcomes for lower levels of mosaicism, although the numbers
were too small for statistical significance. Repeat amniocentesis was not useful in predicting clinical
outcome, although it might be useful when there is an insufficient number of cells or cultures to establish
a diagnosis. The authors suggested PUBS as an adjunct study, as the risk for abnormal outcome
increased with positive confirmation. One of five normal cases were confirmed versus five of eight
abnormal cases. The authors also recommended high-resolution ultrasound.
Mosaicism for trisomies 12 and 20 poses unique problems. For both of these trisomies, mosaicism
has been reported that appeared to have no discernible effect on the fetus or liveborn, and yet in other
cases, the mosaicism was associated with an abnormal outcome. A case report and survey of a decade
of literature (270) showed a total of 13 reported cases in which trisomy 12 mosaicism was observed
in amniocytes. In nine cases, the pregnancy was terminated, and in seven of the nine, no phenotypic
abnormalities were reported. One fetus was not described, and one had only two lobes in each lung
and appeared otherwise normal. In seven cases, confirmatory cytogenetic studies on skin, blood, rib,
placenta, kidney, liver, lung, and/or villi was performed, and in the six cases in which fetal tissue was
known to be cultured, five showed confirmation of mosaic trisomy 12.
In five cases in which the pregnancy was continued after diagnosis of trisomy 12 mosaicism in
amniocytes, the diagnosis was confirmed in urinary cells or skin in two children. One of them had
mild dysmorphic features with near-normal development at 3 years, and the other was dysmorphic
and died in the first weeks of life with cardiac abnormalities. In the other three, the diagnosis was not
confirmed in fetal skin and/or blood; one had normal development at 5 months and the other two died
in the newborn period with heart, kidney vertebral, tracheo-esophageal, and other abnormalities.
It is interesting to note that the terminated fetuses were described as normal and the liveborns were
almost all abnormal. This was not related to degree of mosaicism. It could be the result of unrecognized
abnormalities in second-trimester fetuses, or there could have been a bias toward reporting live
births with congenital abnormalities.
Outcomes of 144 cases of trisomy 20 mosaicism (30) indicate that 112 of 123 cases (91%) were
associated with a normal phenotype; 18 of these were abortuses. In most cases, the cells with trisomy
20 are extraembryonic or largely confined to the placenta. Of the 11 abnormal outcomes, 3 were in
liveborns and 8 in abortuses. Three abortuses with urinary tract abnormalities and two with heart
abnormalities represent the only consistent, serious abnormalities associated with such mosaicism.
Of 21 children followed for 1–2 years, all were normal except for 2 with borderline psychomotor
delay. It was also apparent that attempted cytogenetic confirmation of the finding should not be
limited to analysis of fetal blood, because trisomy 20 has not been observed in blood cells. Confirmation
studies in newborns should be done on placental tissues, skin, cord blood, and urine sediment,
and in abortuses, they should be done on kidney, skin, and placental tissues. Finally, true mosaic
trisomy 20 could be associated with a mild phenotype. A case was reported in which nonmosaic
trisomy 20 was diagnosed by CVS, and the term placental karyotype showed the same finding.
Mosaic trisomy 20 was seen in foreskin cultures and in a second skin culture, whereas lymphocyte
culture chromosomes were 46,XY. Aside from diffuse hypopigmentary swirls along the lines of
Blaschko on his extremities and trunk, he was considered clinically normal at 8 years of age (271).
Trisomy 16 mosaicism has attracted a great deal of interest in the past several years, inasmuch
as it was previously thought that the finding of mosaic or nonmosaic trisomy 16 resulted always in
pregnancy loss; now it is known that this is not always the case. Of recognized conceptions that
spontaneously abort in the first trimester, 6% have trisomy 16 (37). Most conceptuses abort between
8 and 15 weeks’ gestation, and the extra chromosome is usually of maternal meiosis I origin.
The mosaicism is thought to arise from either failure of bivalent formation or the precocious separation
of bivalent homologs, with or without crossing-over, during meiosis I. These unpaired univalents
then enter a second premature division, separating into constituent chromatids. During the
second meiotic division, these chromatids cannot take part in a normal anaphase and would therefore
be partitioned at random (272). This would be misinterpreted as a maternal meiosis I error by