Tri5 2

 , .
17:3: 201–242 (1997)
RARE TRISOMY MOSAICISM DIAGNOSED IN

AMNIOCYTES, INVOLVING AN AUTOSOME
OTHER THAN CHROMOSOMES 13, 18, 20, AND
21: KARYOTYPE/PHENOTYPE CORRELATIONS
 . . 1,2, - 1,  . 3,  .  4,  . 5,
 . 6,  . 7,  . 8,  . 9,
 . 10,  11,  . 12,  13,
 . 14,  . 15,  . 16,  . 17, 
 18
1
Prenatal Diagnosis Laboratory of New York City/Medical and Health Research Association of N.Y., Inc., NY,
U.S.A.; 2New York University School of Medicine, New York City, NY, U.S.A.; 3Genzyme Genetics, Santa Fe,
NM, U.S.A.; 4Henry Ford Hospital, Detroit, MI, U.S.A.; 5University of Connecticut Health Center, Farmington,
CT, U.S.A.; 6University of California, San Diego, CA, U.S.A.; 7Baylor College of Medicine, Houston, TX, U.S.A.;
8
Allina Cytogenetics Laboratory, Minneapolis, MN, U.S.A.; 9SouthWest Genetics, San Antonio, TX, U.S.A.;
10
Brigham & Women’s Hospital, Boston, MA, U.S.A.; 11Children’s Hospital Eastern Ontario, Ottawa, Canada;
12
University of Utah, School of Medicine, Salt Lake City, UT, U.S.A.; 13Credit Valley Hospital, Mississauga,
Ontario, Canada; 14University of Washington, Seattle, WA, U.S.A.; 15Kaiser Medical Center, San Jose, CA,
U.S.A.; 16University of British Columbia, Vancouver, B.C., Canada; 17British Columbia Children’s Hosp.,
Vancouver, B.C., Canada; 18North York General Hospital, Toronto, Canada
Received 20 June 1996

Revised 14 October 1996
Accepted 22 October 1996
SUMMARY
In order to determine the significance of trisomy mosaicism of an autosome other than chromosomes 13, 18, 20,
and 21, 151 such cases diagnosed prenatally through amniocentesis were reviewed. These rare trisomy mosaicism
cases include 54 from 17 cytogenetic laboratories, 34 from a previous North American mosaicism survey, and 63
from published reports. All were cases of true mosaicism with information available on pregnancy outcome, and
with no evidence of biased ascertainment. There were 11 cases of 46/47,+2; 2 of 46/47,+3; 2 of 46/47,+4; 5 of
46/47,+5; 3 of 46/47,+6; 8 of 46/47,+7; 14 of 46/47,+8; 25 of 46/47,+9; 2 of 46/47,+11; 23 of 46/47,+12; 5 of
46/47,+14; 11 of 46/47,+15; 21 of 46/47,+16; 7 of 46/47,+17; 1 of 46/47,+19; and 11 of 46/47,+22. As to the risk
of an abnormal outcome, the data showed a very high risk (>60 per cent) for 46/47,+2, 46/47,+16, and 46/47,+22;
a high risk (40–59 per cent) for 46/47,+5, 46/47,+9, 46/47,+14, and 46/47,+15; a moderately high risk (20–39 per
cent) for 46/47,+12; a moderate risk (up to 19 per cent) for 46/47,+7 and 46/47,+8; a low risk for 46/47,+17; and
an undetermined risk, due to lack of cases, for the remaining autosomal trisomy mosaics. Most cases were evaluated
at birth or at termination, so subtle abnormalities may have escaped detection and developmental retardation was
not evaluated at all. Comparison of the phenotypes of prenatally diagnosed abnormal cases and postnatally
diagnosed cases with the same diagnosis showed considerable concordance. Since the majority of anomalies noted
are prenatally detectable with ultrasound, an ultrasound examination should be performed in all prenatally
diagnosed cases. In cytogenetic confirmation studies, the data showed much higher confirmation rates in cases with
abnormal outcomes than in cases with normal outcomes [81 per cent vs. 55 per cent for fibroblasts (from skin, fetal
tissue, and/or cord); 88 per cent vs. 46 per cent for placental cells; 22 per cent vs. 10 per cent for blood cells]. The
confirmation rate reached 85 per cent when both fibroblasts and placental tissues were studied in the same case (with
trisomic cells found in one or the other, or both). Therefore, one must emphasize that both fibroblasts and placental
Addressee for correspondence: Lillian Y. F. Hsu, MD, Prenatal Diagnosis Laboratory of New York City, 455 First
Avenue—Room 027, New York, NY 10016, U.S.A.
CCC 0197–3851/97/030201–42 $17.50

? 1997 by John Wiley & Sons, Ltd.
202 . . .   .
tissues should be studied. Except for 46/47,+8 and 46/47,+9, PUBS is of limited value for prenatal diagnosis of rare
trisomy mosaicism. DNA studies for UPD are suggested for certain chromosomes with established imprinting
effects, such as chromosomes 7, 11, 14, and 15, and perhaps for chromosomes 2 and 16, where imprinting effects are
likely. ? 1997 by John Wiley & Sons, Ltd.
 : rare trisomy mosaicism; amniocytes; prenatal cytogenetic diagnosis
INTRODUCTION (a) Chromosome mosaicism must have been

diagnosed in a minimum of two independent
Excluding marker chromosomes, true mosaic- culture vessels.
ism involving an autosome accounts for 44–47 per (b) There must be one cell line with a complete
cent of all mosaic cases diagnosed in amniocytes autosomal trisomy (other than 13, 18, 20 and
(Hsu et al., 1992, 1996). In an earlier survey of 277 21) (not a partial trisomy).
autosomal trisomy mosaic cases, 193 cases (70 per (c) There must be a normal cell line.
cent) were mosaic for a common trisomy [trisomy (d) There must be information available on the
20 (103 cases), trisomy 21 (60 cases), trisomy 18 (15 phenotypic outcome of the pregnancy.
cases), and trisomy 13 (15 cases)], whereas 84 cases (e) There may not be evidence of biased ascertain-
(30 per cent) involved a cell line with an autosomal ment, such as a prior abnormal ultrasound
trisomy other than these four better known types finding.
(Hsu et al., 1992). The significance of rare auto-
somal trisomy mosaicism was not fully determined Because of these requirements, many cases of
because of the lack of cases, inadequate infor- rare trisomy mosaicism could not be included in
mation on phenotypic outcome, and limited this review. Therefore, the proportions of various
confirmation studies. categories of trisomy mosaicism do not reflect the
Today it is well recognized that the phenotypic occurrence rates. Information on the following
outcome of a prenatally diagnosed trisomic mosaic items was requested in this collaboration:
case may be influenced by many factors, such as
the possibility of confined placental mosaicism and v Indication for the amniocentesis.
the potential effect of imprinting in uniparental v Maternal age at expected date of delivery.
disomy (UPD) secondary to rescue of an initial v Detailed data on the phenotype, including birth
trisomy (Ledbetter and Engel, 1995). We wished to weight.
review all known cases of rare trisomy mosaicism v Information on gestational age at delivery to rule
diagnosed in amniocytes and to place the available out intrauterine growth retardation.
data into proper perspective for a better under- v Clinical follow-up data on psychomotor devel-
standing of risk and significance. We note some opment of liveborns.
karyotype/phenotype correlations by comparing v Pathology report on abortuses.
the phenotypic abnormalities observed in pre- v Cytogenetic confirmation data, such as PUBS,
natally diagnosed cases with those in postnatally cord blood, cord, fetal or liveborn tissues,
diagnosed cases. placental tissues.
v Other cytogenetic data, such as FISH studies of
MATERIALS AND METHODS interphase nuclei or metaphases.
v Data on molecular studies, including studies of
We reviewed 151 prenatally diagnosed cases of DNA for an evaluation of UPD.
trisomy mosaicism involving an autosome other
than chromosomes 13, 18, 20, and 21 detected in
amniocytes. Fifty-four cases were collected from RESULTS AND DISCUSSION
17 cytogenetic laboratories in this collaboration;
34 were derived from a previous North American Of the 151 cases reviewed, there were 11 cases
chromosome mosaicism survey (Hsu, 1992b) and of 46/47,+2; 2 cases of 46/47,+3; 2 cases of
63 cases were from published reports or abstracts. 46/47,+4; 5 cases of 46/47,+5; 3 cases of 46/47,+6;
In order to have meaningful karyotype/ 8 cases of 46/47,+7; 14 cases of 46/47,+8; 25 cases
phenotype correlations, the following inclusion of 46/47,+9; 2 cases of 46/47,+11; 23 cases of
criteria were established: 46/47,+12; 5 cases of 46/47,+14; 11 cases of
      203
Table I—Outcome of cases with rare autosomal trisomy mosaicisms diagnosed in amnio-
cytes
Abnormal outcomes Abnormal

phenotype
Type Total No. of cases (No. with IUGR) FD/SB
46/47,+2 10/11 (90·9%) 7 (2) 3

46/47,+3 1/2 — 1 0
46/47,+4 1/2 — 1 0
46/47,+5 2/5 (40·0%) 2 (2) 0
46/47,+6 0/3 — 0 0
46/47,+7 1/8 (12·5%) 1 0
46/47,+8 1/14 (7·1%) 1 0
46/47,+9 14/25 (56·0%) 14 (2) 0
46/47,+11 0/2 — 0 0
46/47,+12 6/23 (26·1%) 4 2
46/47,+14 2/5 (40·0%) 2 0
46/47,+15 6/11 (54·5%) 6 (3) 0
46/47,+16 15/21 (71·4%) 15 (8) 0
46/47,+17 0/7 — 0 0
46/47,+19 0/1 — 0 0
46/47,+22 7/11 (63·6%) 6 (2) 1
See Appendix for abbreviations.
46/47,+15; 21 cases of 46/47,+16; 7 cases of was not confirmed in either blood or placental
46/47,+17; 1 case of 46/47,+19; and 11 cases tissue. Two other cases, both with 6 per cent
of 46/47,+22 (Table I). There are no known cases trisomy 2 cells, resulted in intrauterine death (II-6)
of 46/47,+1 or 46/47,+10 diagnosed in amnio- or stillbirth (II-5) and in both cases mosaicism was
cytes. Data on all categories from trisomy 2 confirmed in placental tissue.
mosaics to trisomy 22 mosaics are presented Among the seven cases with an abnormal
according to the numerical sequence (Tables phenotype, cytogenetic confirmation of 46/47,+2
II–XVII); comparison of phenotypic abnormalities was achieved in five cases in which fibroblasts
between prenatal and postnatal cases are shown in and/or placental cells were studied. Three blood
Tables XVIIIa and XVIIIb. Abbreviations are cultures showed only cells with normal karyotypes.
summarized in the Appendix. No confirmation study information was available
on two other cases (Tables II and XIX).
Chromosome 2 is frequently involved in pseudo-
46/47,+2
mosaicism, both in multiple-cell and in single-cell
Eleven cases of 46/47,+2 were collected and cases with trisomy 2 (Hsu, 1992b). However, when
reviewed (Table II). Except for one (II-1), all cases cells with trisomy 2 are found in two or more
resulted in abnormal outcomes: seven abnormal cultures, a diagnosis of true trisomy 2 mosaicism is
offspring, two stillborns and one fetal demise. The established and should be taken seriously. High-
seven phenotypically abnormal offspring included resolution serial ultrasound examination of the
four full-term liveborns, one premature infant, and fetus can be used to detect major abnormalities to
two abortuses. They showed variable phenotypic help the parents make an informed decision about
abnormalities with no specific pattern (Table II). the pregnancy.
Three other cases resulted in stillbirth (two cases) Since non-mosaic trisomy 2 was found in
or intrauterine death (one case). The only case with approximately 5–6 per cent of first-trimester
a normal outcome (II-1) had only 4 per cent spontaneous abortuses (Warburton et al., 1991),
trisomy 2 cells in the amniocytes. It is not known trisomy 2 mosaicism may be a result of a self-
whether the normal outcome should be attributed correction or rescue process from trisomy. Abnor-
to this low percentage of trisomic cells. Mosaicism mal phenotypic outcome may be related to the
Table II—Details of findings for 46/47,+2 mosaicism
204
Amniocytes Pregnancy outcome
Confirmatory Mat. Contributor(s)
Case % Abn Cells studies age or
No. Karyotype cells examined Normal Abnormal (No. of cells) Indication (years) reference
II-1 46,XY/47,XY,+2 4·0% 52 Nl M (LB) Blood—Nl (79) AMA 35 Brothman, A. R.

Placenta—Nl (52) AF89-322
II-2 46,XY/47,XY,+2 NA NA Abn M (AB)—transversal hemimelia NA — — Bui et al., 1984
II-3 46,XY/47,XY,+2 NA NA Abn M (AB)—ambiguous external NA — — Bui et al., 1984
genitalia with a urethral meatus on
the dorsum of the phallus
II-4 46,XY/47,XY,+2 11·8% 17cl Abn M (LB)—high arched palate, Blood—Nl (NA) Questionable 17 Casey et al.,
Fac Dys (low-set ears), simian Cord—Nl (NA) large 1990
creases, widely spaced nipples Placenta—Nl (NA) ventricle
Foreskin—mosaicism by U/S
confirmed
II-5 46,XX/47,XX,+2 6·3% 32cl Stillbirth, F (21 weeks)—no visible Placenta—46(15)/47,+2(5) Elevated 23 Chadwick, D.
birth defects MSAFP A891238
II-6 46,XX/47,XX,+2 6·7% 30cl Intrauterine death Placenta—46(15)/47,+2(5) — — Farrel, S. A.*
03960
II-7 46,XY/47,XY,+2 26·8% 56 Abn M (C-section at 30 weeks)— Blood—Nl (NA) Elevated 19 Golabi et al.,
IUGR, large anterior fontanel, Skin—Nl (NA) MSAFP 1995
prominent occiput, Fac Dys (beak Liver—46(96)/47,+2(4)
. . .   .
nose, flat molar area), brain UPD excluded by DNA

pathology, CHD (DORV, ASD, studies
and VSD), pectus excavatum,
rocker-bottom feet
II-8 46,XY/47,XY,+2 33·0% 40 Abn M (LB)—IUGR At 14 months, Cord blood—Nl (100) Elevated 31 Harrison et al.,
wt and ht <3% HC 3% Amnion—32% 47,+2 MShCG 1995
Chorion—20% 47,+2
Villi—12% 47,+2
Maternal UPD
DX by DNA study
II-9 46,XY/47,XY,+2 23·4% 64 Abn M (AB)—lumbo-sacral spina Skin—Nl (NA) AMA 35 Pappas et al.,
bifida, AFAFP 13 SD above, Muscle—Nl (NA) 1995
AChE (+) Placenta—46(14)/47,+2(6)
Amnion—46(17)/47,+2(3)
II-10 46,XX/47,XX,+2 33·3% 30 Abn F (AB)—dolichocephaly, Lung—46(26)/47,+2(4) Elevated 28 Shaffer, L.
oligohydramnios Placenta—46(24)/47,+2(6) MSAFP #47477
Skin—Nl (50) (4 MOM)
Kidney—Nl (50)
II-11 46,XX/47,XX,+2 20·0% 40 Stillbirth NA — — Uchida, I.*
31625

*Personal communication.
      205
possible imprinting effect in maternal UPD of per cent trisomy 4 cells in amniocytes, resulted in a
chromosome 2; one case with proven maternal normal liveborn who was developmentally normal
UPD 2 showed IUGR, as well as postnatal growth at 1 year of age with normal cells found in PUBS
retardation (II-8) (Harrison et al., 1995). and foreskin. The other case (IV-2), with 31 per
Confined placental mosaicism may very well be cent trisomy 4 cells, resulted in an abnormal
a contributing cause for the fetal death or still- liveborn with MCA, facial dysmorphism, and
births of three cases (II-5, II-6, II-11). This possi- CHD, yet with no significant developmental delay
bility is further supported by the finding of cells at 1 year of age. 46/47,+4 was confirmed in the
with trisomy 2 in the placental cultures in two of forearms and in placental tissue (Tables IV and
these cases. XIX). The fact that cells with trisomy 4 were not
There was one postnatally diagnosed case of detected in blood cultures in IV-2 may explain
46/47,+2 mosaicism. The infant had IUGR, dys- why, in addition to its high lethality, trisomy 4
morphic facies, and a clinical diagnosis of Pfeiffer mosaicism has not been more widely reported
syndrome (Cramer et al., 1993) (Table XVIIIa). postnatally.
46/47,+3
Only two cases were collected in this category 46/47,+5
(Table III). One case (III-1) had 5 per cent of
trisomy 3 cells and resulted in a grossly normal Five cases of 46/47,+5 were reviewed (Table V).
male liveborn. Both PUBS and skin fibroblasts All pregnancies went to term; three resulted in
from foreskin showed only normal karyotypes. grossly normal liveborns and two of these were
The other case (III-2), with 35·7 per cent trisomy developmentally normal at 6–7 months of age.
3 cells, resulted in an abnormal liveborn with Two liveborns were reported to be abnormal with
MCA who died at 18 months of age due to facial dysmorphysm, CHD, and IUGR.
CHD. Trisomy 3 mosaicism was confirmed in In both cases with abnormal phenotypes,
skin fibroblasts and amnion cultures, whereas 46/47,+5 was confirmed: one in cord tissue (V-2)
blood cultures showed only cells with a normal and one in skin and placenta (V-4). Of the three
karyotype. normal-appearing liveborns, two had follow-up
At least three cases of 46/47,+3 have been studies; only cells with a normal karyotype were
diagnosed postnatally (Table XVIIIa). One adult found in blood, skin, and placenta. These limited
was reported to have severe mental retardation, data appear to show a correlation between the
short stature, and dysmorphic facies (Kuhn et al., phenotypic outcome and cytogenetic confirmation
1987). One adult had short stature, coloboma, of 46/47,+5 in fibroblast cultures.
hip dislocation, and Bartter syndrome (DeKeyser Thus far, PUBS does not appear to be helpful
et al., 1988). One infant with minor dysmorphism for work-up of this type of mosaicism. High-
died at 5 months following a severe failure to resolution ultrasound examination, however,
thrive (Metaxotou et al., 1981). In this last case, should be recommended.
blood cells showed only 47,+3 and skin fibroblasts The percentage of trisomy 5 cells in amniocytes
showed only a normal karyotype. seems to have no bearing on the pregnancy
Trisomy 3 mosaicism has been noted in the outcome. This is illustrated especially in case V-3,
discrepancies between chorionic villus sampling where 80 per cent of the amniocytes (from two
(CVS) and amniocytes or fetal chromosomes. In at independent amniocenteses) showed trisomy 5
least eight cases, trisomy 3 mosaicism was found in cells, and the pregnancy resulted in a normal
direct CVS preparations, but not in amniocytes or liveborn with no developmental delay at 6
fetal cells (Hsu, 1992a). It is possible that confined months and with a normal karyotype in somatic
placental mosaicism of trisomy 3 has a phenotypic tissues and placental tissues. It is possible that the
effect on the fetus. As of today, no information trisomy 5 cell line in this case started as an
is available regarding any imprinted genes on extraembryonic event or was confined to the
chromosome 3. placenta because the extra chromosome 5 was
lost from the fetus in a rescue process. Thus
46/47,+4 far, there has been no report of imprinted
Two cases of 46/47,+4 were diagnosed in genes on chromosome 5 (Ledbetter and Engel,
amniocytes (Table IV). One case (IV-1), with 10 1995).
206
Table III—Details of findings for 46/47,+3 mosaicism

III-1 46,XY/47,XY,+3 5·0% 40 Nl M (LB) PUBS—Nl (100) AMA 38 PDL 4543

Foreskin—Nl (40)
III-2 46,XY/47,XY,+3 35·7% 14 Abn M (LB)—bilateral cleft lip and Blood—Nl (100) AMA 42 Wang, H. S.
palate, tetralogy of Fallot, Skin—46(10)/47,+3(5) A15480
. . .   .
pulmonary stenosis, Amnion—46(8)/47,+3(2)

microphthalmia, cataracts, lt ear
hypoplasia, multiple vertebral
abnormalities, severe DD. Death at
18 months due to CHD
Table IV—Details of findings for 46/47,+4 mosaicism

IV-1 46,XY/47,XY,+4 10·0% 20 Nl M (LB) PUBS—Nl (150) AMA 41 Higgins, R. R.

Nl at 1 year FISH—Nl (100 nuclei) A0481
Foreskin—Nl (20)
FISH—Nl (460 nuclei)
Placenta—Nl FISH six sites
(2841 nuclei)
IV-2 46,XX/47,XX,+4 31·0% 60 Abn F (LB)—cutis marmorata, PUBS—Nl (100) AMA 38 Marion et al.,
Fac Dys (prominent forehead, Cord—Nl (50) 1990
low-set ears), short neck, Blood—Nl (52)
pectus excavatum, VSD, Skin—rt arm—46(44)/47,+4(56);
absent rt thumb. At 1 year, lt arm—46(51)/47,+4(49)
no significant DD Placenta—site 1
46(42)/47,+4(18); site 2
46(30)/47,+4(34)
     
207
208
Table V—Details of findings for 46/47,+5 mosaicism

V-1 46,XY/47,XY,+5 23·0% 60 Nl M (LB) PUBS—Nl (100) AMA 38 Casamassima

Nl at 7 months Blood—Nl (103) et al., 1989
V-2 46,XX/47,XX,+5 40·0% 45 Abn F (LB)—low birth weight, Cord—46(92)/47,+5(8) — — Penchaszadeh

systolic murmur, preauricular Blood—Nl et al., 1988
pit
V-3 46,XY/47,XY,+5 78·9% 38cl Nl M (LB) Cord blood—Nl (100) AMA 36 Richkind et al.,
Retap 16cl Nl at 6 months Foreskin—Nl (66) 1987
81·3% Amnion—Nl (100)
Chorion—Nl (100)
Placenta—Nl (105)
. . .   .
V-4 46,XY/47,XY,+5 25·0% 24 Abn M (LB)—IUGR, Fac Dys PUBS—Nl (100) Anxiety 30 Sciorra et al.,
(high square forehead, Cord blood—Nl (106) 1992
hypertelorism, prominent nasal Placenta—46(54)/47,+5(46)
bridge), VSD, diaphragmatic Skin—46(32)/47,+5(8)
eventration, no cooing at 7
months. Died at 9 months
(2 months after heart surgery)
V-5 46,XX/47,XX,+5 6·7% 30 Nl F (LB) NA FH of NTD 34 Shaffer, L.

41788
      209
46/47,+6 than fetal NTDs, such as fetal distress, fetal
death, placental pathology or other fetal/placental
Three cases of low-level trisomy 6 mosaicism conditions (Milunsky, 1992).
were collected (Table VI). All had 6 per cent As to possible imprinted genes on chromosome
trisomy 6 cells in amniocytes and all three resulted 7, it is now quite certain that maternal UPD has
in normal liveborns. One had blood chromosome clinical significance (Ledbetter and Engel, 1995).
studies that showed a normal karyotype in 300 When there is evidence for prenatal and/or post-
cells. No placental tissues were studied. It is poss- natal growth retardation in an infant with a
ible that all three cases were the result of confined prenatal diagnosis of 46/47,+7, a DNA study is
placental mosaicism. suggested to rule out maternal UPD 7 (Langlois
et al., 1995).
46/47,+7
46/47,+8
Eight cases of 46/47,+7 were collected (Table
VII). All eight continued to term. Seven resulted in Fourteen cases of 46/47,+8 were collected
normal liveborns, four of whom had follow-up (Table VIII). One case (VIII-1) that showed 77 per
1
from 4 months to 42 years and were reported to be cent trisomy 8 cells was reported to be abnormal
developmentally normal. Two of these (VII-1 and (with no detailed description and no confirmatory
VII-2, both with follow-up to 4 years of age) had studies). The remaining 13 cases all resulted in
trisomy 7 mosaicism confirmed in foreskin fibro- grossly normal-appearing abortuses (eight cases)
blasts. The only abnormal liveborn (VII-4) showed or liveborns (five cases) with trisomy 8 cells in
mild developmental delay, facial asymmetry, and amniocytes ranging from 3·8 to 40 per cent. The
hypomelanosis of Ito. In this case, amniocytes outcome observation is not surprising, as it is
showed trisomy 7 in all 9 cells of one flask and known that a clinical diagnosis of mosaic or
46,XY in all 30 cells of the other flask. In fact, non-mosaic trisomy 8 in a liveborn is difficult.
while the prenatal diagnosis of 46/47,+7 true Recognition of subtle abnormalities in an abortus,
mosaicism was not really established, 46/47,+7 such as thick lips, prominent ears, absent or dys-
mosaicism was confirmed in the skin fibroblasts at plastic patellae, deep plantar/palmar skin furrows,
age 7 years. or a narrow pelvis could be even more difficult
Placental tissues were studied in two of the seven (Jones, 1988; Schinzel, 1993). There was no
cases with normal outcome; both showed only follow-up information on the five grossly normal
normal cells. liveborns.
Trisomy 7 is known to be a relatively frequent Of eight normal-appearing abortuses, seven had
(non-random) observation in amniocytes, as fibroblast studies and 46/47,+8 mosaicism was
single-cell or multiple-cell pseudomosaicism (fre- found in five. In three cases (all abortuses) with
quency is next to the most common finding of placental studies, trisomy 8 mosaicism was con-
trisomy 2) (Hsu, 1992b). Cells with trisomy 7 firmed in two. Among five cases with PUBS and/or
found in direct CVS preparations have led to blood cultures, cells with trisomy 8 were detected
several cases of discrepancies between CVS and in two (Tables VIII and XIX).
fetal karyotypes (Hsu, 1992a). It would be helpful When a prenatal diagnosis of 46/47,+8 is made
to know how frequently trisomy 7 mosaicism is in amniocytes, PUBS may help to confirm the
confined to the placenta. diagnosis. Yet a finding of only normal cells cer-
Trisomy 7 mosaicism has been diagnosed post- tainly does not rule out trisomy 8 mosaicism and,
natally at least six times (reviewed by Hsu et al., in fact, may provide a false sense of security.
1992; Newlin et al., 1995). Three of these cases Trisomy 8 mosaicism was involved in a few cases
were associated with renal agenesis (Potter with discrepancy between CVS diagnosis and fetal
syndrome) or renal dysplasia (XVIIIa). or amniocyte karyotypes (Hsu, 1992a). In these
Interestingly, among the seven prenatal cases cases, the fetuses all had a normal karyotype and it
with known indication for amniocentesis, an is reasonable to conclude that confined placental
abnormal maternal serum alpha-fetoprotein mosaicism of trisomy 8 can occur. The high prob-
(MSAFP) concentration was noted for four; three ability of identifying a grossly normal-appearing
had elevated MSAFP and one had low MSAFP. offspring after a prenatal diagnosis of 46/47,+8
High MSAFP may reflect conditions other may therefore be related to both the inability to
210
Table VI—Details of findings for 46/47,+6 mosaicism

% Abn Cells studies age or
Case No. Karyotype cells examined Normal Abnormal (No. of cells) Indication (years) reference
VI-1 46,XX/47,XX,+6 6·0% 133 Nl F (LB) NA — — Disteche and Norwood*
VI-2 46,XY/47,XY,+6 6·4% 47 Nl M (LB) Blood—Nl (300) — 29 Padre-Mendoza et al., 1979

. . .   .
VI-3 46,XX/47,XX,+6 6·0% 30 Nl F (LB) NA — — Welborn and Lewis, 1990
Table VII—Details of findings for 46/47,+7 mosaicism

VII-1 46,XY/47,XY,+7 48·0% 25cl Nl M (LB) Blood—Nl (100) Elevated 30 Benn, P. AF9640
Nl at 4 1/2 years Foreskin—46(11)/47,+7(11) MSAFP
VII-2 46,XY/47,XY,+7 36·6% 30 Nl M (LB) PUBS—Nl (203) Elevated 31 Bradshaw, C. and

Retap 33 Nl at 4 years Blood—Nl (100) MSAFP Jones, O. W.
18·2% Foreskin—46(20)/47,+7(18) A1336-91
VII-3 46,XX/47,XX,+7 5·0% 141 Nl F (LB) Blood—Nl (NA) — — Fadness, P.*

Placenta—Nl (NA)
VII-4 46,XY/47,XY,+7 23·0%† 39 Abn M (LB)—at age 7; Blood—Nl (60) Elevated — Jenkins et al.,
mild DD, Fac Dys Skin—46(10)/47,+7(26) MSAFP 1993
(facial asymmetry),
hypomelanosis of Ito
VII-5 46,XX/47,XX,+7 31·3% 16cl Nl F (LB) Retap—Nl (30) Low 31 Neu, R. L.

Cord—Nl (30) MSAFP Case KW
Villi—Nl (20)
VII-6 46,XX/47,XX,+7 26·7% 15cl Nl F (LB) NA Elevated 29 Neu, R. L.

MShCG Case AA
VII-7 46,XY/47,XY,+7 15·0% 20 Nl M (LB) PUBS—Nl (30) AMA 39 Shaffer, L. (41026)

Nl at 25 months
     
VII-8 46,XY/47,XY,+7 11·4% 44 Nl M (LB) NA AMA 37 Van Dyke, D.

Nl at 4 months A94-28241
†Trisomy 7 cells found in all 9 cells in one flask but not in 30 cells of other flask.
211
Table VIII—Details of findings for 46/47,+8 mosaicism
212
VIII-1 46,XX/47,XX,+8 77·0% 27 Abn F (AB)— NA — — Antley, R. A.*

No detail
VIII-2 46,XX/47,XX,+8 NA 8 Nl F (LB) PUBS—46(997)/47,+8(3) Previous 23 Camurri et al.,

cultures Blood—46(993)/47,+8(7) malformed 1988
Skin—Nl (401) child
VIII-3 46,XY/47,XY,+8 8·6% 46 Nl M (AB) Fetal tissues—46(NA)/47,+8(NA) — — Crandall, B.*
VIII-4 46,XY/47,XY,+8 27·2% 14cl Nl M (AB) Kidney—Nl (50) AMA 35 Disteche, C.

Brain—Nl (50) CAC-12339
Placenta—46(47)/47,+8(3)
VIII-5 46,XY/47,XY,+8 40·0% 77 Nl M (AB) Skin—trisomy 8 cells 30% — — Martin, G.,

Placenta—trisomy 8 cells 50% Norwood, T.,
Disteche, C.,
and Salk, D.*
VIII-6 46,XX/47,XX,+8 13·0% 53 Nl F (AB) Fetal tissues—mosaicism confirmed — — Mennutti, M.*

VIII-7 46,XY/47,XY,+8 11·8% 17cl Nl M (LB) PUBS—Nl (50) AMA 35 Neu, R.
Retap—Nl (18cl) Case H.L.
. . .   .
VIII-8 46,XY/47,XY,+8 3·4% 58 Nl M (AB) Skin—46(4)/47,+8(16) AMA 35 PDL 5092
VIII-9 46,XX/47,XX,+8 8·4% 59 Nl F (AB) No growth AMA 39 PDL 6306
VIII-10 46,XX/47,XX,+8 3·8% 52 Nl F (LB) Blood—Nl (50) AMA and 35 PDL 40251
elevated
MSAFP
VIII-11 46,XY/47,XY,+8 28·0% 18cl Nl M (AB) Rt arm—46(70)/47,+8(33) AMA 36 Swisshelm et al.,

Lt leg—46(85)/47,+8(56) 1981
Liver, testis, cord, placenta, brain,
kidney, lung, amnion—Nl (50 each)
VIII-12 46,XY/47,XY,+8 4·0% 100 Nl M (LB) PUBS—Nl (50) AMA 37 Vekemans et al.,
Blood—Nl (50) 1981
VIII-13 46,XY/47,XY,+8 7·5% 40 Nl M (LB) NA — — Welborn and

Lewis, 1990
VIII-14 46,XY/47,XY,+8 37·5% 16cl Nl M (AB) Blood—46(5)/47,+8(5) AMA 36 Wyatt, P. R.

A920290
      213
recognize subtle clinical features of trisomy 8 and skeletal abnormalities, such as a dislocated hip.
the possibility of confined placental mosaicism. Comparison of the major phenotypic abnormali-
ties noted in the prenatal versus the postnatal cases
shows rather comparable features (Table XVIIIa).
46/47,+9 The available prenatal data suggest a high risk,
Twenty-five cases of 46/47,+9 were collected namely 56 per cent (14/25), for the fetus to have a
(Table IX). Twenty-one elected termination. Of noticeably abnormal phenotype.
these, 13 resulted in grossly abnormal abortuses: To date, it appears unlikely that chromosome 9
eight had MCA; two had minor abnormalities (one carries imprinted genes and UPD should not there-
with a short neck and a large mouth; and one with fore be a major concern (Ledbetter and Engel,
the right big toe flexed upward); and no detailed 1995).
information was available for the other three. The
eight remaining abortuses appeared normal.
46/47,+11
Among the four cases that elected to continue
the pregnancy, one resulted in an abnormal live- Only two cases of 46/47,+11 were collected
born with IUGR and features of trisomy 9 syn- (Table X). Both cases had a low degree of
drome (IX-15). The remaining three liveborns (two mosaicism (2·7 and 5·5 per cent) and both resulted
term deliveries and one premature infant) showed in grossly normal offspring (one liveborn and one
no noticeable abnormalities. One liveborn was abortus). The liveborn was developmentally nor-
reported to be developmentally normal at age 3 mal at 15 months. Only cells with a normal karyo-
years 8 months (IX-2). type were found in the confirmatory studies [PUBS
In 14 cases with an abnormal outcome, fibroblast in case X-1 and skin fibroblasts in X-2 (abortus)].
cultures were obtained for eight (seven abortuses No placental tissues were studied.
and one liveborn). All seven fibroblast cultures Trisomy 11 mosaicism has been detected at least
from abnormal abortuses showed trisomy 9 mosai- three times in direct CVS preparations but not
cism and only a normal cell line was found in the in amniocytes or fetal cells of these three cases
abnormal liveborn. In four abnormal cases with (Hsu, 1992a). This suggests that the cases with
blood cultures, three showed 46/47,+9 (two abor- trisomy 11 mosaicism may have reflected confined
tuses and one liveborn) (Tables IX and XIX). placental mosaicism.
Thus, in all nine abnormal cases with confirma- If a prenatal diagnosis of 46/47,+11 is made
tion studies, trisomy 9 mosaicism was confirmed in from a CVS preparation or in amniocytes, one
fibroblast and/or blood cultures, whereas in nine may have to be concerned about the possibility of
cytogenetic confirmation studies of grossly normal UPD, because it is now certain that paternal UPD
offspring, trisomy 9 mosaicism was confirmed in of chromosome 11 shows an imprinting effect
only three [two in fibroblasts (abortuses) and one (Ledbetter and Engel, 1995). At least 15 cases of
in blood (premature infant)]. Trisomy 9 mosaicism paternal UPD 11 have been described in associ-
was found in three out of four placental studies in ation with the Beckwith–Wiedemann syndrome
the normal outcome group and in the only pla- (Ledbetter and Engel, 1995). DNA studies for
centa studied in the abnormal outcome category UPD are suggested.
(Table XIX).
Since cells with trisomy 9 are detectable in blood
cultures and major congenital anomalies including 46/47,+12
IUGR may be diagnosable through an ultrasound Twenty-three cases of 46/47,+12 mosaicism
scan of the fetus, PUBS and a high-resolution were collected (Table XI). Twelve patients opted to
ultrasound examination should be recommended. continue the pregnancy. Of these, two had a fetal
Trisomy 9, mosaic or non-mosaic, is a distinct demise (one with IUGR), one delivered a prema-
clinical entity. Over 40 cases have been diagnosed ture infant with MCA, two resulted in abnormal
postnatally (Arnold et al., 1995; Schinzel, 1993; liveborns with MCA, and the remaining seven
Wooldridge and Zunich, 1995). The major pheno- gave birth to grossly normal liveborns. Among the
typic abnormalities include growth and mental latter, three had follow-up from 5 months to 5
retardation, dysmorphic facies with low-set mal- years and all were reported to be developmentally
formed ears, microphthalmia, a bulbous nose, normal. Eleven patients elected termination. One
CHD (especially VSD), renal anomalies, and abortus was grossly abnormal with MCA; the ten
Table IX—Details of findings for 46/47,+9 mosaicism
214
IX-1 46,XX/47,XX,+9 28·0% 25cl Nl F (AB) Skin—46(51)/47,+9(7) AMA 40 Benn, P. A.

AF-6578
IX-2 46,XX/47,XX,+9 83·9% 31cl Nl F (LB) PUBS—Nl (100) AMA 48 Benn, P. A.
Nl (3 years AF-V-2737
8 months)
IX-3 46/47,+9 NA NA ‘Abn’ (AB) (no details) NA — — Doherty, R.*
(sex not known)
IX-4 46,XX/47,XX,+9 50·0% 48 Abn F (AB) (no details) Placenta—46(2)/47,+9(8) — — Flecker, D.
Fetal tissue—46 (11)/ Garver, K.*
47,+9 (7) 88-141 AF
IX-5 46,XX/47,XX,+9 86·6% 30 Abn F (AB)—MCA, Fac Fetal tissue—46(0)/ — — Golbus, M.*
Dys (micrognathia, low-set 47,+9(5) 10492
ears), GR, ambiguous
external genitalia
IX-6 46,XX/47,XX,+9 24·0% 58 Nl F (LB) Blood—Nl (75) AMA 39 Greenberg et al.,
Amnion—Nl (75) 1982
IX-7 46,XX/47,XX,+9/ 38·0% 31 Abn F (AB)—very short PUBS—46(13)/47,+9(3)/ AMA 40 Herens et al.,
47,XX,+Mar (for 47,+9) (21cl) neck, Fac Dys (large 47,+Mar(34) 1989
38·0% mouth) Blood—46(57)/47,+9(0)/
(for 47,+Mar) 47,+Mar(129)
. . .   .
IX-8 46,XY/47,XY,+9 30·4% 23cl Nl M. Premature Cord blood—46(27)/ AMA 42 Higgins, R. R.

birth (23 weeks) 47,+9(3) 94A1353
520 g. Died at Placenta—all abn.
4 days 47,+9(10)
IX-9 46,XX/47,XX,+9 8·3% 155 Nl F (AB) Skin—Nl (50) AMA 38 Hsu et al., 1978
Lung—Nl (50)
IX-10 46,XX/47,XX,+9 42·0% 40 Abn F (AB)—MCA NA — — Martin, G.,
Norwood, T.,
Disteche, C.,
Salk, D.*
IX-11 46,XX/47,XX,+9 10·0% 39 Nl F (AB) Fetal tissues—Nl (NA) — — Martin, G.,
Norwood, T.,
Disteche, C.,
Salk, D.*
IX-12 46,XY/47,XY,+9 12·0% 102 Abn M (AB)—IUGR, PUBS—Nl (100) AMA 39 Merino et al.,
MCA, hydrocephalus, Skin—46(83)/47,+9(17) 1993. Case B
dolichoecphaly, cystic Lung—46(86)/47,+9(14)
kidney
IX-13 46,XX/47,XX,+9 25·0% 32cl Abn F (AB)—rt big toe Skin and kidney— AMA 39 Morton, C. C.
flexed upward 46(12)/47,+9(8) CB930749
Table IX continued on next page

Table IX—continued from previous page

IX-14 46,XY/47,XY,+9 80·0% 15cl Nl M (AB). All Kidney—46(21)/47,+9(4) AMA 42 Pantzar, T. J.

fetal parts look Villi—28% 47,+9 93-VA575
normal Amnion—33% 47,+9
Chorion—34% 47,+9
IX-15 46,XX/47,XX,+9 15·0% 70 Abn F (LB)—IUGR MCA, Blood—46(20)/47,+9(4) AMA 38 PDL 12076
Fac Dys (no details) Skin—Nl (20)
IX-16 46,XX/47,XX,+9 12·0% 68 Abn F (AB)—MCA, Fac NA AMA 35 PDL 16137
Dys (low-set ears and fish
mouth), thick neck,
bilateral tibia torsion
IX-17 46,XX/47,XX,+9 38·0% 47 Nl F (AB) Blood—Nl (50) AMA 44 Pfeiffer et al.,
Skin—Nl (70) 1984
Placenta—46(0)/47,+9(50)
IX-18 46,XX/47,XX,+9 NA NA Abn F (AB)—no details Mosaicism confirmed in — — Polani et al.,
fetal tissues 1979
IX-19 46,XX/47,XX,+9 NA NA Abn F (AB)—MCA, Fac NA AMA 39 Purvis-Smith
Dys (prominent nose, abn et al., 1983
ears, micrognathia),
pulmonary stenosis, ASD,
bicornate uterus,
dysmorphic hands and feet
IX-20 46,XX/47,XX,+9 25·0% 52 Abn F (AB)—MCA, Fac PUBS—46(99)/47,+9(1) Previous 34 Schwartz et al.,
Dys (micrognathia), Heart—46(38)/47,+9(12) spontaneous 1989
persistence of lt superior Skin—46(28)/47,+9(4) abortion and
vena cava, skeletal Lung—46(39)/47,+9(11) borderline
abnormalities Liver—Nl (31) AMA
IX-21 46,XX/47,XX,+9 58·6% 29 Abn F (AB)—ASD and NA — — Shapiro, L. R.*
     
pulmonary stenosis 541

IX-22 46,XX/47,XX,+9 42·0% 40 Nl F (AB) NA — — Shapiro, L. R.*
LAF3450
IX-23 46,XX/47,XX,+9 7·0% 59 Nl F (AB) NA — — Vekemans, M.*
T182
IX-24 46,XY/47,XY,+9 40·0% 59 Nl M (AB) Skin—Nl (50) — — Yu, C. W.*
IX-25 46,XX/47,XX,+9 85·0% 25 Abn F (AB)—MCA, Fac Skin—46(9)/47,+9(5) AMA 40 Zadeh et al.,
Dys (micrognathia), CHD, 1987
renal abnormalities
215
216
Table X—Details of findings for 46/47,+11 mosaicism

X-1 46,XY/47,XY,+11 2·7% 111 Nl M (LB) PUBS—Nl (100) AMA 35 Jenkins, L. S. A93-3693
Nl at 15 months
. . .   .
X-2 46,XX/47,XX,+11 5·5% 90 Nl F (AB) Skin—Nl (NA) — — Sciorra, L. A.*
      217
remaining abortuses appeared to be normal. For 21 cases, the indication for amniocentesis
Therefore, of the 23 cases, six (26·1 per cent) had was provided. Advanced maternal age was cited
abnormal outcomes (four—MCA; two—fetal for 13, abnormal maternal serum screening for
demise). five (with high MSAFP in four and abnormal
Among these six cases with an abnormal out- triple screen in one), and other reasons for the
come, only three had confirmation studies (Table remaining three. Of the four cases with elevated
XIX). In one case with MCA (XI-21), trisomy 12 MSAFP, two had an abnormal outcome (one
mosaicism was confirmed in skin fibroblasts and abortus with MCA and one fetal demise) and
placental cultures, but not in PUBS and post- two had normal liveborns. These are consistent
natally sampled blood. Two other abnormal cases with the suggestion that unexplained high
had blood studies showing only normal cells. MSAFP is associated with an increased risk for
Among the 17 cases with a normal outcome, 11 an adverse perinatal outcome (Brazeral et al.,
had confirmation studies. Trisomy 12 mosaicism 1994) and fetal aneuploidy (Feuchtbaum et al.,
was found in seven out of ten fibroblast cultures 1995; Kaffe and Hsu, 1992).
(all abortuses), three out of five placental cultures, To our knowledge, only three cases of
and one out of seven blood cultures. The only 46/47,+12 mosaicism have been reported post-
positive blood culture showed only 1 per cent natally (Table XVIIIb). Two had dysmorphism,
trisomy 12 cells (Table XIX). short stature, and scoliosis. One of these was
Combining both abnormal and normal outcome retarded and the other had CHD and abnormal
cases, the cytogenetic confirmation rate of trisomy skin pigmentation, but normal mental develop-
12 mosaicism is eight out of 11 in fibroblast ment. The third was a man with infertility, situs
cultures and four out of six in placental cultures. In inversus, and normal mental development.
any case, PUBS or blood culture seems useless for To date, there have been no reports regarding
the diagnostic work-up. any imprinted genes on chromosome 12 or cases of
In one grossly normal abortus (XI-17), fibro- phenotypic abnormality associated with UPD of
blast studies showed only cells with a normal chromosome 12 (Ledbetter and Engel, 1995).
karyotype, but placental cultures showed cells with
trisomy 12. This case is likely to have been the
result of confined placental mosaicism. Previously 46/47,+14
reported cases in which trisomy 12 mosaicism was Five cases of 46/47,+14 were reviewed (Table
found in CVS cultures and not in fetal cells may XII). Three patients opted to continue the preg-
also have reflected confined placental mosaicism nancy; all resulted in grossly normal liveborns. All
(Hsu, 1992a). three had confirmatory studies on PUBS, blood,
When a diagnosis of 46/47,+12 is made in and/or skin fibroblasts, and all showed only nor-
amniocytes, it should not be taken lightly. The risk mal cells. Two other patients elected termination.
of the fetus being abnormal is much higher than One fetus was found to have hydrocephaly on
that in trisomy 20 mosaicism, which is 9 per cent ultrasound before the termination. The other abor-
(Hsu, 1992b). Again, a high-resolution ultrasound tus had facial dysmorphism and MCA. Neither
examination of the fetus must be recommended. case had confirmatory studies. Placental tissue was
A comparison was made in an attempt to see not studied in any of the five cases.
whether there is a difference between the percent- Thus far, at least 15 cases of 46/47,+14 have
age of trisomy 12 cells in the abnormal outcome been diagnosed postnatally (Fujimoto et al., 1992;
group and the percentage of trisomy 12 cells in the Vachvanichsanong et al., 1991). The major clinical
normal outcome group. features reported are growth and mental retard-
In six cases with an abnormal outcome, the ation, CHD (especially tetralogy of Fallot and
percentage of trisomic cells varied from 23 to 62 septal defects), and body and/or facial asymmetry
per cent (with four cases >40 per cent), whereas (Table XVIIIb). In these postnatally diagnosed
the percentage of trisomic cells varied from 6 to 64 cases, trisomy 14 cells have been found in 4–70
per cent in the 17 cases with a normal outcome per cent of blood cells and in 0–16 per cent of
(with 11 cases ¡20 per cent). Therefore, there may skin fibroblasts. There appears to have been no
be a small tendency for an association between a correlation between the percentage of trisomy 14
higher percentage of trisomy 12 cells and the cells and the severity of the clinical manifestation.
chance of an abnormal outcome. Here PUBS and a high-resolution ultrasound
Table XI—Details of findings for 46/47,+12 mosaicism

218
XI-1 46,XX/47,XX,+12 14·8% 27cl Nl (AB) Fetal tissue—46(37)/ AMA 39 Bradshaw,

Single umbilical 47,+12(3) A1601-92
artery
XI-2 46,XX/47,XX,+12 25·0% 15cl Nl F (AB) PUBS—Nl (100) AMA 42 Cartolano et al.,
Placenta: 1993
Direct—Nl (12)
Cultures—46(41)/
47,+12(31)
Skin—46(14)/47,+12(1)
XI-3 46,XX/47,XX,+12 8·0% 76 Nl F (LB) NA AMA 38 Frohlich and
Retap 200 Nl at 5 months Falk, 1991
0·0%
XI-4 46,XX/47,XX,+12 18·0% 68 Nl F (AB) Rib—46(9)/47,+12(3) Anxiety 32 Jensen et al.,
Cord blood—Nl (215) 1984
Skin—Nl (232)
XI-5 46,XY/47,XY,+12 6·3% 32cl Nl M (LB) NA Abn maternal 34 Khodr, G.
serum triple
screen
XI-6 46,XX/47,XX,+12 64·0% 14 Nl F (LB) Placenta—Site A: Hydramnios 34 Leschot et al.,
Amnio- hypoglycemia 46(55)/47,+12(25) 1988
centesis and seizures Site B: 46(9)/
at 32 Nl at 9 months 47,+12(51)
weeks of Blood—Nl (30)
gestation Skin—Nl (30)
Urine sediment—
. . .   .
46(7)/47,+12(45)
XI-7 46,XX/47,XX,+12 22·0% 36cl Nl F (LB) PUBS—Nl (20) AMA 37 Meck et al., 1994
Nl at 5 years Amnion—Nl (50)
Chorion—Nl (50)
Placenta—Nl (51)
Skin—Nl (100)
XI-8 46,XY/47,XY,+12 33·0% 30 Nl M (AB) Fetal tissue—Nl (NA) — — Mikkelsen, M.*
XI-9 46,XX/47,XX,+12 46·7% 15cl Nl F (AB) NA AMA 38 Neu, R. L.
Case BG
XI-10 46,XX/47,XX,+12 50·0% 24cl Abn F (LB)—CHD (Epstein NA AMA 40 Neu, R. L.
Retaps anomaly) 2nd finger overlaps Case KMcM
53·0% 3rd finger (rt hand)
16·0% Normal psychomotor development
at 8 months
XI-11 46,XX/47,XX,+12 12·5% 16cl Nl F (LB) NA Elevated 25 Neu, R. L.
Retap 61cl MSAFP Case HL
1·6%
XI-12 46,XX/47,XX,+12 20·0% 20cl Nl F (LB) PUBS—Nl (30) AMA 37 Neu, R. L.
Case FB
XI-13 46,XY/47,XY,+12 28·6% 14cl Nl M (LB) NA Elevated 23 Neu, R. L.
MSAFP Case RA
Table XI continued on next page

Table XI—continued from previous page

XI-14 46,XX/47,XX,+12 23·3% 43cl Abn F (AB)—Fac Dys (epicanthus, PUBS—Nl (50) Elevated 31 Neu, R. L.
hypertelorism, broad flat nose, long MSAFP Case JC
philtrum, fish-like mouth), high
arch palate, clinodactyly (rt), deep
transverse palmar creases, short
colon, liver abnormalities, conges-
tive heart failure, large ovaries
with torturous Fallopian tubes
XI-15 46,XX/47,XX,+12 6·1% 98 Nl F (AB) Blood— AMA 37 Park et al., 1991
46(98)/47,+12(1)
Skin—
46(65)/47,+12(2)
XI-16 46,XX/47,XX,+12 45·0% 20 Fetal demise (no pathology report) NA Anxiety 31 PDL 26101
XI-17 46,XX/47,XX,+12 12·5% 56 Nl F (AB) Placenta— Anxiety 32 Petrella and
46(38)/47,+12(1) Hirschhorn,
Kidney—Nl (50) 1990
Skin—Nl (51)
Liver—Nl (18)
XI-18 46,XX/47,XX,+12 32·1% 28cl Fetal demise—IUGR. NA Elevated 30 Van Dyke, D.
No gross abnormalities MSAFP A89-7058
XI-19 46,XX/47,XX,+12 44·0% 16 Abn F (LB)—univentricular heart, PUBS—Nl (100) AMA 38 Von Koskull
hypoplasia of aortic arch, Blood—Nl (30) et al., 1989
preductal aortic coarctation, Placenta—46(0)/
atresia of mitral valve, tricuspid 47,XX,+12(16)
valve insufficiency, Fas Dys (broad Urine sediment—Nl (50)
forehead, small head and anterior Skin—46(15)/47,+12(5)
fontanel, mild hypertelorism,
broad nose, abn ears, down-turned
mouth), high arch palate, long thin
fingers, proximally placed thumbs.
Died at 5 weeks
XI-20 46,XX/47,XX,+12 61·9% 21cl Abn F Premature birth—1710 g at Cord blood—Nl (NA) AMA 39 Watson et al.,
33 weeks. MCA including complex 1988
     
CHD, cataracts, horseshoe kidney,

vertebral abnormalities. Died
shortly after birth
XI-21 46,XX/47,XX,+12 6·3% 32cl Nl F (AB) Subcutaneous tissue— AMA 41 Wyandt et al.,
back-up 30 46(107)/47,+12(2) 1990. Case #1
0·0% Bladder—Nl (70)
Membrane—Nl (34)
Peritoneum—Nl (63)
Lung—Nl (60)
Placenta—Nl (35)
Blood—Nl (97)
XI-22 46,XX/47,XX,+12 11·0% 63 Nl F (AB) Fetal lung— AMA 36 Wyandt et al.,
46(47)/47,+12(3) 1990. Case #2
219
XI-23 46,XX/47,XX,+12 6·7% 60 Nl F (AB) NA AMA 36 Wyandt et al.,

1990. Case #3
220
Table XII—Details of findings for 46/47,+14 mosaicism

No. Karyotype cells examined Normal Abnormal (No. of cells) Indication (years) Comments reference
XII-1 46,XX/47,XX,+14 20·0% 20 Abn F (AB)— NA AMA 35 Khodr, G.

hydrocephaly 5828
XII-2 46,XX/47,XX,+14 10·0% 20cl Nl F (LB) Blood—Nl (53) AMA 38 Neu, R. L.

Case SG
XII-3 46,XX/47,XX,+14 28·6% 21cl Nl F (LB) PUBS—Nl (25) AMA 37 Elevated AFAFP Neu, R. L.
3·6 MOM, AChE Case WMP
(+). Pregnancy
was reported to
have triplets with
2 fetuses resolved
. . .   .
XII-4 46,XY/47,XY,+14 19·0% 58 Abn M (AB)—Fac Dys NA — — Nitowsky, H.*

(low-set ears) simian
lines, clinodactyly,
equinovarus,
rocker-bottom feet,
abn hip (by X-ray)
XII-5 46,XY/47,XY,+14 14·6% 89 Nl M (LB) Blood—Nl (†) AMA 40 Van Dyke, D.

Skin—Nl (†) A81-380
†(Combined 246
cells)
Foreskin—Nl (NA)
      221
examination may be helpful for diagnosis and trisomy 15 cells and one had 31 per cent. It seems
counselling. that a higher percentage of trisomy 15 cells (¢40
An imprinting effect in maternal UPD 14 has per cent) tends to be associated with an abnormal
now been documented and is possible in paternal outcome. This association appears to hold in
UPD 14 (Ledbetter and Engel, 1995). Unless DNA fibroblast cultures.
studies are performed, a normal karyotype in Trisomy 15 was observed in 8 per cent of all
the fetus or liveborn after a prenatal diagnosis trisomic first-trimester abortuses (Warburton
of 46/47,+14 does not rule out the possibility et al., 1991), yet it is rare in liveborns. Non-mosaic
of UPD. trisomy 15 was reported only twice (Coldwell
The finding of hydrocephaly in one case (XII-1) et al., 1981; Kuller and Laifer, 1991). One infant
is compatible with the clinical features reported in died at 4 days of age and one at 9 h. Mosaic
a case with maternal UPD 14 (Healey et al., 1994). trisomy 15 was reported in six infants (Table
Unfortunately, no DNA studies were performed in XVIIIb). All six of these cases had facial dysmor-
this case. phism; three had CHD (one had multiple heart
defects), skeletal anomalies, and/or hypotonia.
Since imprinting effects are known for both
46/47,+15
maternal and paternal UPD 15 (Ledbetter and
Eleven cases of 46/47,+15 were collected (Table Engel, 1995), DNA studies for UPD are suggested
XIII). Six resulted in abnormal offspring (five when a prenatal diagnosis of 46/47,+15 is estab-
abortuses; one liveborn). Of these, three (two lished (ASHG/ACMG Report, 1996). In fact,
abortuses; one liveborn) had multiple heart DNA studies of two of the abortuses reviewed here
defects; one abortus had malrotation of the intes- (XIII-4 and XIII-6) showed maternal UPD 15.
tine and a two-vessel cord. Two abortuses had Both fell into the abnormal outcome category (one
IUGR; one of them had arrhinencephaly, contrac- had IUGR and the other had malrotation of the
tures of the hands, and low-set ears; the other had intestine, and both had abnormal umbilical cords).
narrowing of the proximal segment of the cord. The finding of maternal UPD 15 is associated
Trisomy 15 mosaicism was confirmed in all six with Prader–Willi syndrome. Had these two
cases (six in fibroblasts; four in placental cells) fetuses gone to term, they would presumably have
(Tables XIII and XIX). developed Prader–Willi syndrome.
The five remaining cases were associated with Here, high-resolution ultrasound examination
grossly normal outcomes (three liveborns, one must be re-emphasized. CHD, especially when
premature infant, and one abortus). Trisomy 15 there are multiple heart defects, should be
mosaicism was, however, confirmed in fibroblasts detectable.
and placental cells of only one liveborn (XIII-11).
Blood cultures of two other normal-appearing 46/47,+16
liveborns yielded only normal cells (Table XIX). Twenty-one cases of 46/47,+16 were collected
Cells with trisomy 15 have been detected in (Table XIV). Thirteen patients opted to continue
lymphocyte cultures and have led to the diagnosis the pregnancy. Among these 13 pregnancies, eight
of trisomy 15 mosaicism in one liveborn (Coldwell resulted in phenotypically abnormal offspring (five
et al., 1981) and in one third-trimester fetus term births; three premature infants); five liveborns
(through cordocentesis) (Bennett et al., 1992). were reported to be normal. Eight patients elected
However, in four cases diagnosed in amniocytes, termination: seven of these resulted in phenotypi-
successful blood cultures showed cells with trisomy cally abnormal abortuses and one was reported to
15 in only one case (XIII-1). Therefore, PUBS be grossly normal. Thus, 15 out of 21 cases (71·4
appears to be of limited value. per cent) resulted in abnormal offspring. Thirteen
The percentage of trisomy 15 cells in amniocytes had some dysmorphic features; ten had CHD
was compared with the outcome of pregnancy. Of (most often VSD or ASD, next often double out-
six abnormal outcome cases, five had ¢40 per cent let of the right ventricle). The other features in-
trisomy 15 cells and one had 9·8 per cent trisomy cluded skeletal anomalies in six, gastrointestinal
15 cells in the cultures from an initial amnio- anomalies in five, renal anomalies in four, and
centesis and 5·9 per cent trisomy 15 cells in the other abnormalities (Table XVIIIb).
cultures from a second amniocentesis. Among five It is known that trisomy 16 is one of the most
normal outcome cases, four had six per cent or less common chromosome abnormalities found in
Table XIII—Details of findings for 46/47,+15 mosaicism
222
XIII-1 46,XX/47,XX,+15 66·0% 24 Abn F (AB)—IUGR, Fac CVS (direct)—46(4)/ AMA 38 DNA studies Christian et al.,
Retap 30 Dys (low-set ears, 47,+15(7) ruled out 1996. Case #2
37·0% arrhinencephaly), CVS—(culture)47,+15(6) UPD 15
contractures of Blood—46(25)/47,+15(5)
metacarpal–phalangeal Skin—46(12)/47,+15(8)
joints (bilateral)
XIII-2 46,XY/47,XY,+15 6·0% 50 Nl M NA AMA 35 DNA studies Christian et al.,

premature ruled out 1996. Case #3
infant at UPD 15
28 weeks
XIII-3 46,XX/47,XX,+15 55·5% 36 Abn F (AB)—Fac Dys Skin—46(18)/47,+15(23) AMA 39 Gimelli et al.,
Retap 154 (facial hypertrichosis, Lung—46(12)/47,+15(5) 1983
29·2% low dorsal hairline, Kidney—(lt) 46(63)/
hypertelorism, upward 47,+15(11)
eye slanting, epicanthal Kidney—(rt) 46(23)/
folds, short philtrum, 47,+15(0)
macrostomia, large Intestine—46(17)/
posteriorly rotated ears), 47,+15(3)
CHD (A–V canal, VSD,
persistent ostium
primum), malrotation of
intestine, megapelvis of
. . .   .
rt kidney, Meckel’s
diverticulum
XIII-4 46,XX/47,XX,+15 9·8% 81 Abn F (LB)—IUGR, (BW Placenta—(3 sites) AMA 40 Lahdetie and
Retap 34 1420 g at 39 weeks), 46(15)/47,+15(183) Lakkala, 1992
5·9% CHD (hypoplastic lt Amnion—46(9)/47,+15(8)
ventricle, mitral atresia, Cord—46(111)/47,+15(10)
aortic stenosis, ASD, Cord blood—Nl (100)
VSD, PDA). Died at 13
days
XIII-5 46,XY/47,XY,+15 31·2% 48 Nl M (AB) NA — — Patil, S.*
XIII-6 46,XX/47,XX,+15 44·4% 27 Abn F (AB)—malrotation Skin—47,+15(10) AMA 37 DNA studies Rocklin et al.,
of intestine, 2-vessel cord Lung—47,+15(10) Previous showed 1994
Kidney—Nl (10) child with maternal Elder, F.*
Membranes—46(7)/ Down UPD 15
47,+15(3) syndrome
Blood—FISH 3 signals
(18%) (189 nuclei)
Table XIII continued on next page

Table XIII—continued from previous page

XIII-7 46,XX/47,XX,+15 64·0% 78 Abn F (AB)—CHD by Cord—46(11)/47,+15(14) AMA 35 Sundberg et al.,

serial echocardiograms Skin—46(7)/47,+15(18) 1994
(hypoplastic lt ventricle, Amnion—Nl (30)
VSD, PDA, mitral Placenta—no growth
atresia, narrow aorta).
No post-mortem
pathology examination
XIII-8 46,XX/47,XX,+15 39·3% 28 Abn F (AB)—IUGR, Skin—46(8)/47,+15(2) AMA 43 DNA studies Van Dyke, D.
narrowing of proximal Cord—46(5)/47,+15(5) of abortus A95-32064
segment of cord Villi—46(5)/47,+15(4) tissue showed
Membrane—46(4)/ maternal
47,+15(6) UPD 15
XIII-9 46,XX/47,XX,+15 6·1% 49 Nl F (LB) Blood—Nl (30) Positive 35 Van Dyke, D.

Placenta—Nl (30) MSAFP A95-33621
profile
XIII-10 46/47,+15 (sex 5·9% 51 Nl (LB) Blood—Nl (50) — — Worton and

not recorded) Stern, 1984
XIII-11 46,XY/47,XY,+15 3·6% 83 Nl M (LB) Cord blood—Nl (200) — — Ying, K. L.*

Retap 200 Placenta—sac: 46(14)/ A85-285
1·0% 47,+15(36)
     
Amnion—46(7)/47+15(43)
Chorion—46(4)/47,+15(41)
Cord—46(47)/47,+15(3)
223
Table XIV—Details of findings for 46/47,+16 mosaicism
224
XIV-1 46,XY/47, 69·2% 26cl Abn M (AB)—ASD (by Blood—Nl (100) Elevated 33 UPD not Benn, P. A.
XY,+16 ultrasound), clinodactyly Skin—Nl (100) MShCG likely 1995
Rt leg—Nl (100) Elevated with DNA Tantravahi
Lt leg—Nl (100) MSAFP studies et al., 1996
Placenta—46(2)/
47,+16(5)
XIV-2 46,XX/47, 13·2% 38cl Abn F (AB)—IUGR, Fac Dys Kidney—Nl (75) AMA 36 DNA studies Bradshaw, C.
XX,+16 Retap 33cl (midface malformation with Skin—Nl (75) showed and
3·0% recessed orbits, depressed nasal Placenta—Nl (75) maternal Jones, O. W.
bridge, underdeveloped maxilla), UPD 16 A 0498-93
VSD, severe hypoplasia of
lungs, thymic atrophy, adrenel
atrophy, single umbilical artery
XIV-3 46,XX/47, 8·0% 50 Nl F (LB) NA — — Bernstein, R.*

XX,+16 Nl at 17 8983A
months
XIV-4 46,XX/47, 15·8% 19cl Abn F (AB)—Fac Dys (low-set NA Elevated 35 Davies et al.,
XX,+16 posteriorly rotated ears), MSAFP 1995.
horseshoe kidney, 2-vessel Case #1
umbilical cord
. . .   .
XIV-5 46,XX/47, 37·5% 16cl Abn F (AB)—malrotated gut, PUBS—46(198)/ Elevated 35 DNA studies Davies et al.,
XX,+16 DORV, ectopic rt kidney, Fac 47,+16(2) MSAFP and of skin 1995.
Dys (absent rt external ear MShCG fibroblasts Case #3
canal) showed
maternal
UPD 16
XIV-6 46,XX/47, 96·2% 52 Abn F—premature infant (33 Blood—Nl (NA) Not clear 28 Devi et al.,
XX,+16 weeks), Fac Dys (prominent rt Skin—Trisomy 16 1992
frontal-parietal cranium, in 9% of cells
metopic synostosis, (rt flank) and 1%
plagiocephaly, low-set and (lt flank)
scalloped rt ear), glaucoma
(rt eye), absent rt nipple,
hypoplastic rt chest,
dextrocardia, bilateral simian
creases, camptodactyly of the
4th and 5th fingers, thoracic
scoliosis, sacral dimple,
pulmonary hypoplasia. Died at
11 days
Table 14 continued on next page

Table XIV—continued from previous page

XIV-7 46,XY/47, 20·0% 25cl Abn M (AB)—Fac Dys (mild Blood—Nl (NA) AMA 37 DNA studies Garber et al.,
XY,+16 rhizomelic shortening of legs, Fascia—Nl (NA) showed 1994.
bowing of both femurs, bilateral Skin—46(48)/ maternal Case #1
simian lines, clinodactyly, 47,+16(2) UPD 16
micrognathia) Placenta— 46(18)/
47,+16(32)
XIV-8 46,XX/47, 9·7% 31cl Abn F—Premature C-section Placental biopsy Abnormal 27 Abnormally Garber et al.,
XX,+16 Retap 23cl infant, Apgar 6, 8, IUGR, VSD, 47,+16(17) triple large 1994.
4·0% ASD, minor dysmorphic (direct prep) maternal placenta. Case #2
features including a perineal Placenta—long-term serum DNA studies
groove, a sacral dimple, a single culture Nl (NA) screening. ruled out
umbilical artery, Meckel’s Skin—Nl (NA) Elevated UPD 16
diverticulum, bifurcated lt Amnion—46(25)/ MShCG
ureter, single coronary artery 47,+16(1)
from pulmonary artery
XIV-9 46,XX/47, 30·0% 20cl Abn F (LB)—IUGR, PUBS—46(99)/ Elevated 33 DNA studies Hajjianpour
XX,+16 Retap 100 microcephaly, Fac Dys (facial 47,+16(1) MSAFP excluded et al., 1992
0·0% asymmetry, low-set prominent Blood—Nl (300) UPD 16 Hajjianpour,
ears, downward slant of eyes, Skin—Nl (75) 1995
high arched palate), pectus FISH—3% (3 signals)
excavatum, widely spaced in 800 nuclei
nipples, tapering fingers, large
hyperpigmented skin spots. At
age 28·5 months: mild
developmental and speech delay
XIV-10 46,XY/47, 51·7% 29cl Abn M (AB)—VSD, minor PUBS—Nl (50) AMA 37 Huff et al.,
XY,+16 dysmorphic features, small Placenta—46(4)/ 1991
adrenals and kidneys 47,+16(16)
XIV-11 46,XY/47, 3·3% 123 Nl M (LB) Chorionic villi AMA 36 DNA studies Kalousek, D.
XY,+16 Born 36 weeks. 46(22)/47,+16(1) showed 92.95
Wt 3 lbs 7 oz. Chorionic plate maternal
     
Except for 46(1)/47,+16(19) UPD 16

hypospadias, Amnion—Nl (20)
he shows normal Term villi—direct prep
development at FISH—3 signals in
13 months 95% cells (760 nuclei)
XIV-12 46,XY/47, 20·0% 20cl Abn M (AB)—Fac Dys (long PUBS—Nl (20) AMA 40 Morton, C.
XY,+16 philtrum, thin vermillion border, Skin—Nl (20) CR910671
mild hypertelorism), tetralogy of Placenta—46(25)/
Fallot 47,+16(3)
XIV-13 46,XY/47, 10·0% 30cl Nl M (LB) NA AMA 35 Neu, R. L.

XY,+16 Retap 78cl Case JH
1·3%
225
Table XIV continued on next page

Table XIV—continued from previous page
226
XIV-14 46,XX/47, 52·9% 17cl Abn F (LB)—IUGR, Fac Dys Blood—Nl (103) ‘Lemon-shaped’ 28 DNA studies Lindor et al.,
XX,+16 (low-set lt ear, lt preauricular Placenta—47,+16(30) skull by showed 1993
pit), dolichocephaly. Head looks Skin—46(24)/ ultrasound† maternal
normal at 14 months. Normal 47,+16(6) UPD 16
psychomotor development
XIV-15 46,XY/47, 38·6% 44 Abn M (LB)—IUGR, Blood—Nl (100) Elevated 30 DNA studies Pletcher et al.,
XY,+16 brachycephaly, Fac Dys (broad Skin—46(88)/ MSAFP ruled out 1994.
flat nasal bridge, low-set 47,+16(12) UPD Case #1
posteriorly rotated ears, small Cord—46(6)/
palpebrae, ptosis), short neck, 47,+16(66)
widely spaced nipples, Placenta—46(17)/
second-degree hypospadias, 47,+16(2)
DORV and PDA
XIV-16 46,XX/47, 31·1% 45 Abn F (LB)—IUGR, CHD PUBS—Nl (100) AMA 35 Pletcher et al.,
XX,+16 (DORV, VSD, ASD, PDA, Blood—Nl (50) 1994.
coarctation of aorta), Fac Dys Skin #1—46(94)/ Case #2
(ptosis, small palpebrae, broad 47,+16(1)
nasal bridge) dolichocephaly, Skin #2—46(35)/
camptodactyly, hypertonia. 47,+16(40)
Died during post-cardiac
surgery
XIV-17 46,XX/47, 92·3% 39 Nl F (LB) Placenta—46(16)/ AMA 40 Richkind, K.*
XX,+16 Retap 15cl 47,+16(25) 86012716
. . .   .
73·3%
XIV-18 46,XX/47, 10·0% 20 Abn F (LB)—C-section at 34 Blood—Nl (NA) Elevated 26 Roeder et al.,
XX,+16 weeks. IUGR, Fac Dys Skin—46(26)/ MSAFP 1994
(prominent occiput, triangular 47,+16(14) Hershey, D.*
facies), limb hypoplasia, bowel Placenta—46(1)/
obstruction, small VSD. At 21 47,+16(19)
years, gross motor skill delay.2
No mental retardation
XIV-19 46,XY/47, 36·0% 50 Nl M (AB) Blood—Nl mosaicism Elevated 30 Rosenblum-Vos
XY,+16 found in skin MSAFP et al., 1993
and lung
XIV-20 46,XX/47, 5·0% 40 Nl F (LB) NA — — Warburton,
XX,+16 D.*
XIV-21 46,XX/47, 31·8% 22cl Abn F—Premature infant at 35 PUBS—Nl (NA) AMA 43 Watson et al.,
XX,+16 weeks. IUGR, wt 950 g, renal Cord blood—Nl (NA) 1988
anomalies, imperforate anus, Skin—Nl (NA)
pulmonary hypoplasia Placenta—Nl (NA)
Amnion—trisomy 16
(20%)
Cord—trisomy 16
(70%)
†Case XIV-14 is included in this survey due to the abnormal ultrasound finding not being a clear-cut ‘lemon-shaped skull’ case.
      227
first-trimester spontaneous abortuses. It was ultrasound examinations for a more definitive
observed in 31 per cent of all trisomic abortuses in assessment. PUBS is of very limited value.
one large study (Warburton et al., 1991). Trisomy Since there is evidence to suggest a possible
16 mosaicism was also the most common chromo- imprinting effect in maternal UPD 16 (Ledbetter
some mosaicism detected in all chromosomally and Engel, 1995), DNA studies for UPD were
mosaic abortuses. Trisomy 16 (non-mosaic and performed in nine cases with a prenatal diagnosis
mosaic) constitutes 20 per cent of all chromosomal of 46/47,+16 mosaicism (Table XIV). Five cases
abnormalities in first-trimester abortuses. Due to showed maternal UPD 16; four of these (three
the high lethality of trisomy 16, there has, so far, abortuses; one liveborn) had an abnormal out-
been no liveborn diagnosed to have non-mosaic come: two had MCA, two had IUGR (one was
trisomy 16. Two cases of mosaic trisomy 16 have also dysmorphic); one liveborn appeared normal
been diagnosed postnatally (Gilbertson et al., (at 13 months) but had hypospadias. UPD was
1990; Greally et al., 1990). Both cases showed excluded in four cases (two term liveborn, one
IUGR and CHD; one also had dysmorphic premature infant, and one abortus); all four were
features and MCA (Table XVIIIb). phenotypically abnormal, with IUGR and MCA
Among the prenatal cases, 11 out of 15 in the in three cases and CHD in the fourth. Thus,
abnormal outcome group had 20 per cent or more because almost all cases with or without maternal
trisomy 16 cells, whereas four of the six cases with UPD 16 were phenotypically abnormal, the limited
a normal outcome had 10 per cent or less trisomic data on UPD studies in trisomy 16 mosaicism in
cells. The proportion of trisomic cells in the two amniocytes show no significant difference between
groups overlaps and the small difference noted UPD cases and non UPD cases in the effect on
may not be meaningful. phenotypic outcome.
Of 15 cases with an abnormal outcome, 14 had Among 17 cases with available information
confirmatory studies. Trisomy 16 mosaicism was regarding the indication for amniocentesis,
confirmed in fetal or liveborn tissues in nine cases elevated MSAFP and/or MShCG were listed in
(seven out of 12 fibroblast studies and two out of eight (elevated MSAFP without testing MShCG
12 blood cultures). Cells with trisomy 16 were in five; elevated MShCG and MSAFP in two,
found in nine out of ten placental tissues. and elevated MShCG alone in one). All but one
Of nine cases in which both fibroblasts and of these had an abnormal outcome. However,
placental cells were studied, five showed trisomy 16 seven out of nine cases with other indications
cells in both cultures and three showed trisomy 16 (eight with AMA and one with a ‘lemon-shaped
cells in the placenta but not in fibroblasts, suggest- skull’) also resulted in abnormal offspring. It is
ing the possibility of confined placental mosaicism. known that elevated MSAFP and/or MShCG
One case showed only normal cells in both may suggest an increased risk for an adverse
tissues. perinatal outcome (Brazerol et al., 1994; Benn
Among 6 cases with a normal outcome, two et al., 1996). High MSAFP, as well as high
liveborns had placental tissue studies and in both MShCG in trisomy 16 mosaicism, implies a poss-
cases, cells with trisomy 16 were found; one abor- ible association between these two findings
tus showed trisomy 16 cells in both skin and lung (Vaughan et al., 1994; Zimmerman et al., 1995).
fibroblasts. Three other liveborns did not have It is especially interesting to note that the level of
confirmatory studies. This information indicates MShCG in 46/47,+16 mosaicism is extremely
that in the diagnosis of 46/47,+16 from amnio- high (Benn et al., 1995).
centesis, there is a high probability that placental
cells will show trisomy 16. Confined placental
mosaicism of trisomy 16 has been a frequent cause 46/47,+17
of diagnostic discrepancies between CVS and fetal Seven cases of 46/47,+17 were collected (Table
karyotypes: at least 12 instances are known (Hsu, XV). All seven resulted in grossly normal offspring
1992a). (six liveborns; one abortus). Four liveborns had
Nevertheless, based on the available prenatal follow-up information ranging from 10 to 18
data, a diagnosis of trisomy 16 mosaicism in months and all were reported to be develop-
amniocytes indicates a high risk for fetal abnor- mentally normal. The percentage of trisomy 17
malities. A high-resolution ultrasound of the cells varied from 5 to 25 per cent in six cases and
fetus must be recommended. One may need serial was 88 per cent in the seventh case (XV-4: 100 per
228
Table XV—Details of findings for 46/47,+17 mosaicism

XV-1 46,XY/47,XY,+17 19·1% 68 Nl M (LB) Blood—Nl (100) AMA 36 Djalali et al., 1991
Nl at 18 months
XV-2 46,XY/47,XY,+17 6·5% 62 Nl M (LB) PUBS—Nl (NA) — — Hersch, J.*

Nl at 10 months
XV-3 46,XY/47,XY,+17 10·7% 28cl Nl M (LB) NA AMA 34 Neu, R. L. Case P.S.

Retap 22
9·1%
XV-4 46,XX/47,XX,+17 100·0% 26cl Nl F (LB) Blood—Nl (30) Elevated 22 Neu, R. L. Case P.K.
Retap 20cl N1 at 1 year MSAFP
. . .   .
75·0%
XV-5 46,XX/47,XX,+17 25·0% 40 Nl F (AB) Abortion fluid— AMA 35 PDL 7608

Nl (60)
XV-6 46,XX/47,XX,+17 9·1% 87 Nl F (LB) Blood—Nl (NA) — — Shaham, M. and

Nl at 1 year Shah, H. O.*
XV-7 46,XX/47,XX,+17 5·0% 168 Nl F (LB) Blood—Nl (NA) — — Wilson et al., 1989
Amnion—Nl (NA)
Table XVI—Details of findings for 46/47,+19 mosaicism

Case No. Karyotype cells examined Normal Abnormal (No. of cells) Indication (years) Comments reference
XVI-1 46,XX/47,XX,+19 3·0% 60 Nl F (LB) NA AMA 35 PDL 13198

     
229
Table XVII—Details of findings for 46/47,+22 mosaicism
230
XVII-1 46,XX/47, 18·2% 11cl Abn F (LB)—Fac Dys Skin—46(1)/ — — Dawson, L.*
XX,+22 (abnormal ears), CHD 47,+22(9)
XVII-2 46,XX/47, 28·0% 60 Abn F—Neonatal death Fibroblasts—46(2)/ — — Minka, D. and
XX,+22 IUGR, hydrocephaly 47,+22(18) Jackson, M.*
C-571-88
XVII-3 46,XY/47, 20·0% 15cl ‘Nl’ M (AB) NA AMA 39 Neu, R. L.
XY,+22 Case SJM
XVII-4 46,XY/47, 5·0% 40 Nl M (LB) NA AMA 37 PDL 16467
XY,+22 Retap 40
0·0%
XVII-5 46,XX/47, 7·5% 53 Nl F (AB) Kidney—Nl (19) — — Howard-
XX,+22 Blood—Nl (100) Peebles, P.*
Lung—Nl (31)
Skin—Nl (45)
Placenta—Nl (100)
XVII-6 46,XY/47, 14·0% 100 Abn M (AB)—Fac Dys Skin—46(NA)/ — — Priest, J.*
XY,+22 (low-set large ears, facial 47,+22(NA)
asymmetry) long fingers, Placenta—all cells
simian line with trisomy 22
XVII-7 46,XX/47, 10·0% 20cl Nl F (LB) PUBS—Nl (100) Previous — Richkind, K.*
. . .   .
XX,+22 Cord blood—Nl child 86007633

(100) with
Placenta—Nl (100) NTD
XVII-8 46,XX/47, 28·0% 50 IUGR, normal-appearing PUBS—Nl (360) AMA 47 Stioui et al.,
XX,+22 Retap 41 C-section at 33 weeks Amnion—Nl (17) 1989
31·7% BW 1100 g Blood—Nl (200)
Apgar 8 at 10 min Fibroblast—Nl (200)
Chorionic villi all cells
with trisomy 22
XVII-9 46,XX/47, 3·6% 56 Abn F (AB)—Fac Dys (short Amnion—Nl (48) AMA 34 Van Dyke, D.
XX,+22 nose, cleft lip, long philtrm,
posteriorly rotated ears),
finger-like thumbs, cubitus
valgus, genu recurvatum
XVII-10 46,XX/47, 16·7% 12cl Abn F (LB)—Fac Dys Blood—Nl (30) AMA 44 Wang, H. S.
XX,+22 (bilateral ear tags), tetralogy Placenta—46(18)/ A920459
of Fallot, microcephaly, 47,+22(2)
DD. At 141 months motor
skills—7–8 2months
XVII-11 46,XX/47, 20·0% 10 Fetal demise—15 weeks’ NA — — Welborn and
XX,+22 gestation Lewis, 1990
      231
Table XVIIIa—Phenotypic abnormalities in mosaicism diagnosed postnatally vs. prenatally
46/47,+2 46/47,+3
Postnatal Prenatal Postnatal Prenatal
1 case 10 cases 3 cases 1 case

1 (F) Infant with Fetal death 3 1 (F) Infant with Bilateral cleft lip and
IUGR, hypertelorism, MCA with IUGR prominent forehead, palate, tetralogy of
midface hypoplasia, Fac Dys, CHD 1 low-set malformed Fallot, pulmonary
frontal bossing, Fac Dys and other ears, glaucoma, stenosis,
craniosynostosis, minor clenched hands and microphthalmia,
‘Pfeiffer syndrome’, abnormalities 1 overlapping fingers, cataracts, left ear
scoliosis (blood— NTD 1 PDA. Died at 5 hypoplasia, multiple
46,XX; skin—trisomy Ambiguous genitalia 1 months vertebral
2 in 40%) Hemimelia 1 (Metaxotou et al., 1981) abnormalities, DD.
Dolichocephaly 1 Died at 18 months
IUGR and postnatal 1 (F) 32-year-old with due to CHD
GR 1 severe MR, short
stature, microcephaly,
high forehead, small
flat midface, short
philtrum, simian lines,
dislocated hips,
scoliosis, short neck
and petus excavatum
(Kuhn et al., 1987)
1 (F) 21-year-old with

Bartter syndrome,
short stature,
coloboma, dislocated
left hip
(Cramer et al., 1993) (DeKeyser et al., 1988)
46/47+7 46/47,+9
6 cases 1 case >40 cases 14 cases

Potter syndrome 2 Facial asymmetry, GR, MR, cranial facial MCA 8
Renal dysplasia 1 hypomelanosis of Ito, dysmorphism such as Fac Dys 7
Goldenhar syndrome mild DD low-set malformed CHD 4
with unilateral radial ears, microphthalmia, IUGR 3
hypoplasia 1 bulbous nose Uro-genital
Mental illness (mother CHD especially VSD abnormalities 3
and daughter) 1 Renal abnormalities Skeletal abnormalities 3
MCA with CHD and Skeletal abnormalities No details 3
hypomelanosis of Ito 1 such as hip
dislocation
(Arnold et al., 1995;

(Newlin et al., 1995) Schinzel, 1993;
(quoted in Hsu et al., Wooldridge and Zunich,
1992) 1995)

232 . . .   .
Table XVIIIb—Phenotypic abnormalities in mosaicism diagnosed postnatally vs. prenatally (continued)
46/47,+12 46/47,+14
3 cases 6 cases 15 cases 2 cases

1 (F) with MR, Fac Fetal demise 2 GR 1 with Fac Dys (low-set
Dys, short stature, CHD 4 MR ears), equinovarus,
microcephaly, Fac Dys 2 Broad nose rocker-bottom feet,
scoliosis, and muscle Skeletal abnormalities 2 Abn and/or low-set ears abn hip
atrophy Renal abnormalities 1 Micrognathia
(Patil et al., 1983) Large mouth 1 with hydrocephaly
Short neck
1 (F) with Fac Dys, CHD
short stature, Body asymmetry
scoliosis, CHD, abn Abn skin pigmentation
skin pigmentation Micropenis and
and normal mental cryptorchidism
development
(English et al., 1994)
1 (M) with infertility,

situs inversus, and
normal mental
development
(Richer et al., 1977) (Fujimoto et al., 1992)
46/47,+15 46/47,+16
6 cases 6 cases 2 cases 15 cases

Fac Dys 6 IUGR 3 1 girl with multiple CHD IUGR 8
CHD (one with multiple CHD (all 3 cases had (including VSD, PDA, Fac Dys 11
heart defects) 3 multiple heart defects; coartation of aorta), CHD 10
Hypotonia 3 1 also had MCA, IUGR and postnatal VSD or ASD 6
Skeletal abnormalities 3 renal and GR DORV 3
IUGR 2 gastrointestinal (Greally et al., 1990) Tetralogy of Fallot 1
Hydrops 1 abnormalities 3 Dextrocardia 1
Malrotation of intestine 2 1 male infant with Skeletal abnormalities 5
Fac Dys 2 IUGR, Fac Dys Gastrointestinal
Arrhinencephaly 1 (cranial asymmetry, abnormalities 5
abn scalp hair pattern, Renal abnormalities 4
hypertelorism, Psychomotor delay 2
coloboma of left iris, Microcephaly 1
(Bühler et al., 1996; short nose, flat nasal Skin pigmentation 1
Coldwell et al., 1981; bridge, low-set abn
Fryns et al., 1993; ears), VSD, musculo-
Kuller and Laifer, 1991; skeletal abnormalities
Milunsky et al., 1996; (scoliosis, overlapping
Stallard and Sommer, fingers, etc.)
1989) (Gilbertson et al., 1990)
Table XVIIIb continued on next page

      233
Table XVIIIb—continued from previous page
46/47,+22
Postantal* Prenatal
19 cases 7 cases
IUGR IUGR 2
Microcephaly Fac Dys or abn ears or
Hypoplastic or low-set ears ear tags 3
Hypoplastic midface CHD 2
Cleft palate and/or lip DORV 1
Webbed neck/redundant Long fingers 2
skin Cleft lip 1
CHD Microcephaly 1
Renal abnormalities Hydrocephaly 1
Ear pits/tags Skeletal abnormalities 1
Hypertelorism Facial asymmetry 1
(Bacino et al., 1995) Fetal death 1
*Includes 47,+22 and

46/47,+22
See Appendix for abbreviations
cent in cells from an initial amniocentesis and 75 46/47,+19

per cent in cells from a second amniocentesis).
Six cases with confirmation studies (including Only one case is known to us (Table XVI). The
four with PUBS or blood studies, one abortion pregnancy resulted in a phenotypically normal
fluid, and one case with blood and amnion studies) liveborn. Unfortunately, neither follow-up studies
showed only normal cells. It seems that trisomy 17 nor developmental evaluation was possible.
cells are likely to be of extraembryonic origin and Trisomy 19 was not observed in first-trimester
not representative of the fetus. studies of abortuses (Warburton et al., 1991), yet
Previous data showed that chromosome 17 is mosaic trisomy 19 was diagnosed at least twice
one of six chromosomes that tend to show a postnatally (Chen et al., 1981; Rethore et al.,
non-random involvement in multiple cell trisomy 1981). In both of these cases, facial dysmorphism
pseudomosaicism (Hsu, 1992b). This observation was the major finding. One presented as a still-
is compatible with the suggestion of confined born and one died neonatally. Cells with trisomy
placental mosaicism. In fact, in one CVS 19 were recovered in blood cultures in both
case, trisomy 17 mosaicism was established cases. Therefore, for further work-up of a prenatal
to be confined to the placenta (Kalousek et al., diagnosis of such mosaicism, PUBS could be
1987). considered.
Nevertheless, trisomy 17 mosaicism in the fetus
is compatible with survival to term. It has been 46/47,+22
diagnosed at least twice postnatally (Bullerdiek
and Bartnitzke, 1982; Shaffer et al., 1996). One Eleven cases of 46/47,+22 were collected (Table
case was a newborn with severe malformations and XVII). Seven (63·6 per cent) had an abnormal
the other was a boy with MR, growth retardation, outcome, including two liveborns with CHD and
seizures, autism, microcephaly, and hearing loss. dysmorphic features, one neonatal death with
Therefore, when a diagnosis of 46/47,+17 is IUGR and hydrocephaly, one Caesarean section
established in amniocytes, it should not be taken premature infant (33 weeks) with IUGR, two
lightly. abortuses with dysmorphic features and/or skeletal
Table XIX—Cytogenetic confirmation of trisomy mosaicism in different categories of phenotypic outcome
234
Total cases
Phenotypic outcome Cytogenetic confirmation confirmed studied
Abnormal
Fibroblasts Total
Abnormal Fetal death Fibroblasts Placenta and cases from Normal Abnormal
Type Normal phenotype or SB only only placenta* tissues Blood NA outcome outcome
46/47,+2 1 0/1 0/1 0/1 0 0/1

7 1/1 1/1 3/3 5/5 0/3 2 5/5
3 2/2 2/2 1 2/2
46/47,+3 1 0/1 0/1 0/1 0 0/1
1 1/1 1/1 0/1 0 1/1
46/47,+4 1 0/1 0/1 0/1 0 0/1
1 1/1 1/1 0/1 0 1/1
46/47,+5 3 0/1 0/1 0/2 1 0/2
2 1/1 1/1 2/2 0/2 0 2/2
46/47,+6 3 0/1 2 0/1
46/47,+7 7 2/2 0/1 0/1 2/4 0/4 2 2/5
1 1/1 — — 1/1 0/1 0 1/1
46/47,+8 13 3/5 3/3 6/8 2/5 2 8/11
1 1
46/47,+9 11 1/4 1/2 2/2 4/8 1/4 2 4/9
14 6/7 1/1 7/8 3/4 5 9/9
. . .   .
46/47,+11 2 0/1 0/1 0/1 0/2

46/47,+12 17 4/5 4/5 8/10 1/7 6 8/11
4 1/1 1/1 0/3 1 1/3
2 2
46/47,+14 3 0/1 — — 0/1 0/3 0 0/3
2 2
46/47,+15 5 0/1 1/1 1/2 0/3 2 1/3
6 1/1 5/5 6/6 2†/3 0 6/6
46/47,+16 6 1/1 2/2 — 3/3 0/1 3 3/3
15 3/3 1/1 8/9 12/13 2‡/12 1 13/14
46/47,+17 7 0/1 0/1 — 0/2 0/5 1 0/6
46/47,+19 1 1
46/47,+22 4 0/1 0/1 0/2 0/2 2 0/2
6 2/2 1/2 2/2 5/6 0/2 0 5/6
1 1
26/37 8/15 33/39 67/91 11/73 26/61 46/50
Totals 84 59 6 70·3% 53·3% 84·6% 73·6% 15·1% 42·6% 92·0%
*Confirmation in either one or both tissues.

†Interphase FISH in one case.
‡Low frequency of trisomy cells.
      235
Table XX—Overall cytogenetic confirmation in cases with normal vs. abnormal outcome
Normal Abnormal
Fibroblasts 18/33 (54·5%) 33/41 (80·5%)

Placental cells 11/24 (45·8%) 28/32 (87·5%)
Both fibroblasts and placental cells* 5/15 (33·3%) 16/24 (66·7%)
Fibroblasts or placental cells or both* 10/15 (71·4%) 23/24 (95·8%)
Blood 4/41 (9·8%) 7/32 (21·9%)
*When both tissues were studied.
anomalies, and one fetal demise at 15 weeks’ abnormal ears, ear tags, webbed neck/redundant
gestation. skin, CHD, and long fingers. Again, ultrasound
Four cases (two liveborns; two abortuses) had examination is essential in the work-up.
two or more features of trisomy 22 syndrome, such
as abnormal ears or ear tags, CHD, and long
fingers (Table XVIIIb). Four cases had a normal Cytogenetic confirmation studies
outcome (two liveborns and two abortuses). The
percentage of trisomy 22 cells ranged from 3·6 to The cytogenetic confirmation studies of trisomy
28 per cent for the seven cases with an abnormal mosaicism in fibroblasts, placental cells, fibro-
outcome and from 5 to 20 per cent for the four blasts and placental cells (in the same case) and
cases with a normal outcome. Thus, there was no blood cells, including PUBS and cord blood (Table
noticeable difference in the proportion of abnor- XIX), are summarized according to ‘normal out-
mal cells between the cases with an abnormal come’ versus ‘abnormal outcome’ in Table XX.
outcome and those with a normal outcome. The combined data show much higher confir-
As to the cytogenetic confirmation of trisomy 22 mation rates in cases with abnormal outcomes
mosaicism, six of the abnormal outcome group than in cases with normal outcomes, with 80·5 per
had confirmation studies. Cells with trisomy 22 cent versus 54·5 per cent for fibroblasts, 87·5 per
were found in three fibroblast cultures (out of four cent versus 45·8 per cent for placental cells, 66·7
studied) (XVII-1, XVII-2, XVII-6) and in placental per cent versus 33·3 per cent for simultaneous
cells in three cases (out of four studied) (XVII-6, studies and confirmation on both fibroblasts and
XVII-8, XVII-10). One case (XVII-6) showed placental cells, and 21·9 per cent versus 9·8 per cent
trisomy 22 cells in both fibroblasts and placental for blood cells. The overall confirmation rates were
cells (Table XIX). Thus, trisomy 22 mosaicism 73·6 per cent for tissues and 15·1 per cent for
was confirmed in five of seven cases with an blood cells (Table XIX), but when fibroblasts and
abnormal outcome. Among four cases with a placental cells were studied simultaneously, the
normal outcome, there were two cases with con- finding of trisomy cells in one or the other or both
firmatory studies (one with fibroblasts, placental was 84·6 per cent. Therefore, we must emphasize
cells, and blood; and one with placental cells and that for cytogenetic confirmation, both fibroblasts
blood). Only cells with a normal karyotype were and placental tissues should be studied. There is a
found. good chance (95·8 per cent) that for cases with an
Although trisomy 22 is the second most com- abnormal outcome, trisomic cells will be detected
mon autosomal trisomy found in first-trimester in either fibroblasts or placental cells or both
spontaneous abortuses (Warburton et al., 1991), (Table XX).
liveborns with trisomy 22 (non-mosaic or mosaic) Blood cultures (and/or PUBS) are not a good
have occasionally been reported. In the last 25 tissue source for cytogenetic confirmation. Except
years, trisomy 22 has been diagnosed postnatally for cases with trisomy 8, 9, 13, 18, and 21 mosaic-
over 20 times (Hsu et al., 1971, 1992; Bacino et al., ism, PUBS should not be recommended for fur-
1995). The major clinical features associated with ther evaluation of an established diagnosis of
trisomy 22 syndrome are IUGR, microcephaly, mosaicism in amniocytes.
236 . . .   .
Fig. 1—Relationship between the percentage of trisomy cells in amniocytes and the
phenotypic outcome
Effect of the percentage of cells with a trisomy on more likely to be associated with an abnormal
the phenotypic outcome outcome than those with a low proportion of tri-
somic cells (Fig. 1) (a median of 11·00 per cent for
The data on the percentage of cells with a tri-
normal outcomes versus a median of 29·00 per cent
somy in 145 cases were recorded for a statistical
for abnormal outcomes; a mean of 21·20 per cent
comparison. They were categorized as having a
‘normal outcome’ versus an ‘abnormal outcome’. for normal outcomes versus a mean of 33·05 per
The study included nine cases of 46/47,+2, two cent for abnormal outcomes). Since the overlap is
notable and the standard deviations are large, the
cases of 46/47,+3, two cases of 46/47,+4, five cases
difference observed here should be interpreted with
of 46/47,+5, three cases of 46/47,+6, eight cases of
caution.
46/47,+7, 13 cases of 46/47,+8, 22 cases of 46/
47,+9, two cases of 46/47,+11, 23 cases
of 46/47,+12, five cases of 46/47,+14, 11 cases of CONCLUSION
46/47,+15, 21 cases of 46/47,+16, seven cases of The overall data indicate that the risk for an
46/47,+17, one case of 46/47,+19, and 11 abnormal outcome, including phenotypically
cases of 46/47,+22. It appears that cases with a abnormal offspring and/or IUGR and/or fetal
relatively high proportion of trisomic cells are demise or stillbirth, varies for mosaic trisomies of
      237
different chromosomes. Since the majority of the Block Grant. We would like to thank Eva Kahn
cases in this review were evaluated either at birth for the helpful suggestions, Shichuan Lu for prep-
or at termination, subtle abnormalities may have aration of Fig. 1, and Josephine Benabu for prep-
escaped detection and developmental or postnatal aration of the manuscript. We are grateful to the
growth retardation would not be diagnosed. It is following geneticists, cytogeneticists, and physi-
critical for all liveborns with a prenatal diagnosis cians for providing or collecting the valuable data:
of trisomy mosaicism to have long-term Antley, R. M., Blue Ridge Radiology Assoc.,
follow-up for developmental evaluation. Morganton, NC; Bernstein, R., University of
To avoid biased ascertainment, cases with prior California, Irvine, CA; Cramer, D., Henry Ford
abnormal ultrasound findings were excluded in Hospital, Detroit, MI; Crandall, B. F., UCLA
this review. However, the possibility of preferential Medical Center, Los Angeles, CA; Dawson, L.,
reporting of cases with an abnormal outcome still Ottawa, Ontario, Canada; Doherty, R., Founda-
exists; this could cause some exaggeration of the tion Blood Research, Scarborough, ME; Elder, F.,
abnormal outcome rate. In this review, 35 (53·0 per University of Texas Health Center, Houston, TX;
cent) of the 66 cases with an abnormal outcome Fadness, P., Buffalo, NY; Farrell, S. A., Credit
were derived from publications, whereas 25 (29·4 Valley Hospital, Ontario, Canada; Flecker, D.,
per cent) of the 85 normal outcome cases were Western Penn. Hospital, Pittsburgh, PA; Garver,
abstracted from published reports. K. L., Verona, PA; Golbus, M. S., University of
In categories with five or more cases, the data California, San Francisco, CA; Hersch, J. H.,
showed a wide range of risk (from 0 to 91 per cent) Child Evaluation Center, Louisville, KY; Hershey,
(Table I). The risks for abnormal outcome are very D., Prenatal Diagnosis Center, Sacramento, CA;
high (>60 per cent) for 46/47,+2, 46/47,+16, and Howard-Peebles, P. N., Genetics and IVF
46/47,+22; high (40–59 per cent) for 46/47,+5, Institute, Fairfax, VA; Jones, O. W., University of
46/47,+9, 46/47,+14, and 46/47,+15, and moder- California, San Diego, La Jolla, CA; Martin, G.,
ately high (26 per cent) for 46/47,+12. In catego- University of Washington, Seattle, WA; Mengden,
ries with a small number of cases (three cases or G. A., Southwest Genetics, San Antonio, TX;
less), the risk was not well defined. However, the Mennutti, M., University of Pennsylvania,
finding of one out of two cases with an abnormal Philadelphia, PA; Mikkelsen, M., John F.
phenotype in 46/47,+3 and 46/47,+4 mosaicism Kennedy Institute, Glostrup, Denmark; Minka,
may suggest a high risk. D., Denver, CO; Nitowsky, H. M., Albert Einstein
Since phenotypic manifestations of prenatally College of Medicine, Bronx, NY; Norwood, T.,
diagnosed cases and postnatally diagnosed cases University of Washington, Seattle, WA; Patil,
are quite comparable and major abnormalities are S. R., University of Iowa Hospital, Iowa City, IA;
detectable with high-resolution ultrasound, this Priest, J., Shodair Hospital, Helena, MT; Richkind,
procedure should be performed in all prenatally K., Integrated Genetics, Santa Fe, NM; Salk, D.,
diagnosed cases. University of Washington, Seattle, WA; Sciorra,
As to the cytogenetic confirmation studies of L., Robert Wood Johnson Medical School, New
other tissues, except for trisomy 8 or trisomy 9 Brunswick, NJ; Shah, H. O., North Shore Hospital,
mosaicism, PUBS is of limited value as part of a NY; Shaham, M., North Shore Hospital, NY;
work-up. The confirmation rate reaches 85 per Shapiro, L. R., Westchester County Medical
cent when both fibroblasts and placental tissues Center, Valhalla, NY; Uchida, I., McMaster
are studied. University, Ontario, Canada; Vekemans, Michel
Lastly, since imprinting effects are documented J. J., currently with Hopital Necker Enfants
for several chromosomes, DNA studies for UPD Malades, Paris, France; Warburton, D., Columbia
are recommended for 46/47,+7, 46/47,+11, Presbyterian Medical Center, NY; Ying, K. L.,
46/47,+14, and 46/47,+15. DNA studies for UPD Seal Beach, CA; Yu, C. W., University of
are suggested for 46/47,+2 and 46/47,+16 where Mississippi Medical Center, Jackson, MS.
imprinting effects are likely.
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AChE acetylcholinesterase
754.
AFAFP amniotic fluid alpha-fetoprotein
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FISH fluorescence in situ hybridization
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GR growth retardation
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An Atlas. Oxford: Oxford University Press. ht height
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(1988). Trisomy 16 and 12 confined chorionic LB liveborn
mosaicism in liveborn infants with multiple lt left
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(Abstract #1006). mat maternal
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states in amniotic fluid using the in situ colony tech- MR mental retardation
nique, Clin. Genet., 38, 14–20. MSAFP maternal serum alpha-fetoprotein
Wilson, M.G., Lin, M.S., Fujimoto, A., Herbert, W., MShCG maternal serum human chorionic
Kaplan, F.M. (1989). Chromosome mosaicism in gonadotrophin
6000 amniocenteses, Am. J. Med. Genet., 32, 506–513.
MOM multiple of mean
Wooldridge, J., Zunich, J. (1995). Trisomy 9 syndrome:
NA not available
report of a case with Crohn disease and review of the
literature, Am. J. Med. Genet., 56, 258–264. Nl normal
Worton, R.G., Stern, R. (1984). A Canadian collabora- NTDs neural tube defects
tive study of mosaicism in amniotic fluid cell cultures, pat paternal
Prenat. Diagn. (Special Issue), 4, 131–144. PDA patent ductus arteriosus
Wyandt, H.E., Maher, T., Fisher, N.L., Patil, S.R., PDL Prenatal Diagnosis Laboratory of New
Osella, P., Luthardt, F.W., Kawada, C., Williamson, York City
R., Milunsky, A. (1990). Trisomy 12 mosaicism in PUBS periumbilical blood sampling
242 . . .   .
rt right U/S ultrasound
SB stillbirth/stillborn VSD ventricular septal defect
SD standard deviation wt weight
UPD uniparental disomy

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17:3: 201–242 (1997)

RARE TRISOMY MOSAICISM DIAGNOSED IN

Received 20 June 1996

CCC 0197–3851/97/030201–42 $17.50

INTRODUCTION (a) Chromosome mosaicism must have been

Abnormal outcomes Abnormal

46/47,+2 10/11 (90·9%) 7 (2) 3

See Appendix for abbreviations.

II-1 46,XY/47,XY,+2 4·0% 52 Nl M (LB) Blood—Nl (79) AMA 35 Brothman, A. R.

nose, flat molar area), brain UPD excluded by DNA

See Appendix for abbreviations.

Table III—Details of findings for 46/47,+3 mosaicism

Amniocytes Pregnancy outcome

III-1 46,XY/47,XY,+3 5·0% 40 Nl M (LB) PUBS—Nl (100) AMA 38 PDL 4543

pulmonary stenosis, Amnion—46(8)/47,+3(2)

Amniocytes Pregnancy outcome

IV-1 46,XY/47,XY,+4 10·0% 20 Nl M (LB) PUBS—Nl (150) AMA 41 Higgins, R. R.

Table V—Details of findings for 46/47,+5 mosaicism

Amniocytes Pregnancy outcome

V-1 46,XY/47,XY,+5 23·0% 60 Nl M (LB) PUBS—Nl (100) AMA 38 Casamassima

V-2 46,XX/47,XX,+5 40·0% 45 Abn F (LB)—low birth weight, Cord—46(92)/47,+5(8) — — Penchaszadeh

V-5 46,XX/47,XX,+5 6·7% 30 Nl F (LB) NA FH of NTD 34 Shaffer, L.

Table VI—Details of findings for 46/47,+6 mosaicism

Amniocytes Pregnancy outcome

VI-1 46,XX/47,XX,+6 6·0% 133 Nl F (LB) NA — — Disteche and Norwood*

VI-2 46,XY/47,XY,+6 6·4% 47 Nl M (LB) Blood—Nl (300) — 29 Padre-Mendoza et al., 1979

VI-3 46,XX/47,XX,+6 6·0% 30 Nl F (LB) NA — — Welborn and Lewis, 1990

Amniocytes Pregnancy outcome

VII-2 46,XY/47,XY,+7 36·6% 30 Nl M (LB) PUBS—Nl (203) Elevated 31 Bradshaw, C. and

VII-3 46,XX/47,XX,+7 5·0% 141 Nl F (LB) Blood—Nl (NA) — — Fadness, P.*

VII-5 46,XX/47,XX,+7 31·3% 16cl Nl F (LB) Retap—Nl (30) Low 31 Neu, R. L.

VII-6 46,XX/47,XX,+7 26·7% 15cl Nl F (LB) NA Elevated 29 Neu, R. L.

VII-7 46,XY/47,XY,+7 15·0% 20 Nl M (LB) PUBS—Nl (30) AMA 39 Shaffer, L. (41026)

VII-8 46,XY/47,XY,+7 11·4% 44 Nl M (LB) NA AMA 37 Van Dyke, D.

VIII-1 46,XX/47,XX,+8 77·0% 27 Abn F (AB)— NA — — Antley, R. A.*

VIII-2 46,XX/47,XX,+8 NA 8 Nl F (LB) PUBS—46(997)/47,+8(3) Previous 23 Camurri et al.,

VIII-3 46,XY/47,XY,+8 8·6% 46 Nl M (AB) Fetal tissues—46(NA)/47,+8(NA) — — Crandall, B.*

VIII-4 46,XY/47,XY,+8 27·2% 14cl Nl M (AB) Kidney—Nl (50) AMA 35 Disteche, C.

VIII-5 46,XY/47,XY,+8 40·0% 77 Nl M (AB) Skin—trisomy 8 cells 30% — — Martin, G.,

VIII-6 46,XX/47,XX,+8 13·0% 53 Nl F (AB) Fetal tissues—mosaicism confirmed — — Mennutti, M.*

VIII-8 46,XY/47,XY,+8 3·4% 58 Nl M (AB) Skin—46(4)/47,+8(16) AMA 35 PDL 5092

VIII-9 46,XX/47,XX,+8 8·4% 59 Nl F (AB) No growth AMA 39 PDL 6306

VIII-11 46,XY/47,XY,+8 28·0% 18cl Nl M (AB) Rt arm—46(70)/47,+8(33) AMA 36 Swisshelm et al.,

VIII-13 46,XY/47,XY,+8 7·5% 40 Nl M (LB) NA — — Welborn and

VIII-14 46,XY/47,XY,+8 37·5% 16cl Nl M (AB) Blood—46(5)/47,+8(5) AMA 36 Wyatt, P. R.

IX-1 46,XX/47,XX,+9 28·0% 25cl Nl F (AB) Skin—46(51)/47,+9(7) AMA 40 Benn, P. A.

IX-8 46,XY/47,XY,+9 30·4% 23cl Nl M. Premature Cord blood—46(27)/ AMA 42 Higgins, R. R.

Table IX continued on next page

Amniocytes Pregnancy outcome

IX-14 46,XY/47,XY,+9 80·0% 15cl Nl M (AB). All Kidney—46(21)/47,+9(4) AMA 42 Pantzar, T. J.

pulmonary stenosis 541

Table X—Details of findings for 46/47,+11 mosaicism

Amniocytes Pregnancy outcome

X-2 46,XX/47,XX,+11 5·5% 90 Nl F (AB) Skin—Nl (NA) — — Sciorra, L. A.*

Amniocytes Pregnancy outcome

XI-1 46,XX/47,XX,+12 14·8% 27cl Nl (AB) Fetal tissue—46(37)/ AMA 39 Bradshaw,

Table XI continued on next page

Amniocytes Pregnancy outcome