European Human Genetics Conference 2007 June 16 – 19, 2007 ...

Prenatal diagnosis
between prenatally diagnosed trisomy 21 incidences with the indications
throughout 7 years.
The indications of the women who underwent cytogenetic prenatal
analysis including amniocentesis (9737), chorionic villus sampling (95)
and fetal blood sampling (229) were evaluated. The mean maternal
age was 34.70±6.02 years and the mean gestation week was 17±3.85.
Advanced maternal age was the most common indication (48.6%) in
all prenatally diagnosed DS cases which is followed by abnormal ultrasound
findings (18.6%) and increased maternal serum screening
in triple test results (18.6%). Trisomy 21 was detected in a total of 70
cases. Chromosome analysis revealed 33 cases with 47,XY,+21; 32
cases with 47,XX,+21; 2 cases with 47,XX,+21,inv(9)(p11;q13), one
with mosaic DS 47,XY,+21/48,XY,+3,+21, one with 46,XY,t(13;15)(q12
;p11),+21 and one 46,XX,t(14;21).The distribution of the number of DS
cases according to the advancing years were: 3/515 (0.003%) in 2000,
5/717 (0,697%) in 2001, 7/836 (0.837%) in 2002, 8/1285 (0.622%) in
2003, 21/1474 (1.424%) in 2004, 13/1316 (0.987%) in 2005, 13/1315
(0.988%) in 2006.
The mothers less than 35 years old who had a fetus with DS covered
47.8% of the cases, nevertheless, when the age lowered to 30 years,
the ratio became 80.6%. The risk of having a child with DS increased
in a gradual, linear fashion until 30 years old and showed a significant
increase thereafter.
P0449. Down’s syndrome screening in Saint-Petersburg. Ten
years experience (1997-2006).
T. K. Kascheeva 1 , Y. A. Nikolaeva 1 , N. V. Vokhmyanina 2 , T. V. Kuznetzova 1 , O.
P. Romanenko 2 , V. S. Baranov 1 ;
1 Ott’s Institute of Obstetrics and Gynecology RAMS, Saint-Petersburg, Russian
Federation, 2 City Medical Genetic Center, Saint-Petersburg, Russian Federation.
Trisomy 21 or Down’s syndrome is one of the most common genetic
abnormalities with its risk progressively increase with maternal age.
In many countries biochemical screening programs have been implemented,
and the risk of Down’s syndrome is calculated for each pregnancy.
Total biochemical screening for Down’s syndrome in Saint-Petersburg
has been carried out in the second trimester of pregnancy
since 1997. Assessment of risk relies maternal age and serum markers
(AFP and HCG) concentrations. Also all pregnant women were
subjected to ultrasound examinations on the 10-14 & 20-22 weeks of
gestation and also for cytogenetic screening for chromosomal abnormalities.
Basic results of screening programs for Down’s syndrome
since 1997 up to 2006 and some urgent problems in this area are outlined.
Since 1997 36,9% DS fetuses (198/536) could be attributed to
the women of 35 ages and more. Most of these cases - 61 % (102/166)
were detected prenatally. Efficiency of DS detection in this group increased
from 28.9% in 1997-98 up to 68% in 2004-06. About 18,7% of
elder women rejected invasive PD for different reasons. Detection rate
in 2-d trimester was 74,6% (cut off 1/360, FPR 6,8%). Since 2004 combined
biochemical & US screening in the first trimester was initiated.
Detection rate was 93.8% (30/32) (cut off 1/250, FPR 12.8%, average
age 32.4+/-4.7). Pilot study of UE3 and inhibin A concentrations were
performed for establishing of medians. Introducing of quadrotest will
be useful for reducing of false positive results for the patients tested in
the 2-d trimester.
P0450. Further results evaluation for the women with increased
risk for congenital anomalies of fetus after biochemical prenatal
diagnostic (PRISCA)
R. Sereikiene, D. Serapinas, V. Asmoniene;
Kaunas Medical University Hospital, Kaunas, Lithuania.
PURPOSE: to evaluate real outcomes of pregnancy of women with
increased risk of fetal chromosomal abnormalities after I or II trimester
biochemical examination more than age risk.
METHODS AND RESULTS: Analyzing of medical documentation, contacts
with women after birthing. The 371 women were examined by the
PRISCA program during 2005.10.01-2006.10.01 year period. The risk
factors were older age, not favorable anamnesis of pregnancy (congenital
anomalies, miscarriages, sterilities and others), not favorable
anamnesis of family or relatives. First trimester “double” test (PAPP-A
+ β-hCG) was done for 103 women, second trimester “triple” test was
done for 268 and all two tests - for 24 women.
The increase risk for Downy and Edwards syndromes was got in 91
(24,5%) cases, according first trimester test - for 26, second - 63, two
this - 12 women. The amniocentesis was offered in case when risk
was higher 1:100 for women younger 40 years old and 1: 50 older 40
years old. This procedure was done for 15 women and 3 trisomies of
chromosome 21(3,3% of all women with increased risk) were found
using FISH method in combination with full cariotype of fetus. In other
74 cases of increased risk the further ultrasound examination was offered.
CONCLUSION: The greet importance is to evaluate the health status
of newborns after birth and all outcomes of pregnancy in cases of
increased risk according biochemical examination. These dates will
show in full text of this work.
P0451. Prenatal diagnosis of trisomy 21 mosaicism with true
chimerism
C. Gug, G. Budau;
University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania.
The 32 year old female (gesta 1, para 0) had amniocentesis at 21
weeks gestation due to: increased nuchal translucency at ultrasound
scan (6 mm at 13 weeks of pregnancy), abnormal alpha-feto-protein
in maternal serum (0,44 MoM) and chromosomal abnormality in family
history (an uncle with Down Syndrome). Chromosome analysis of
amniotic fluid cultures showed a mosaic karyotype: 47,XX+21/46,XY.
The couple was counseled for prenatal diagnosis of the mosaicism: we
explained the possibility that the anomalous cell line could involve fetal
tissues. To exclude the possibility of contamination with maternal cells
(having suspected that a mosaicism with a very low line with no phenotypical
modifications existed), we performed maternal karyotype,
which turned out to be normal. After such investigations, the couple
elected to terminate the pregnancy. Cord blood cultures showed two
cell-lines: a normal cell-line of 46,XY and a 47,XX+21 cell line. We
propose that this case represents an example of true chimerism. The
most plausible mechanism underlyind this phenomenon is that two
embryos (1 normal, male, and one trisomic, female) have performed a
fusion in early pregnancy.
P0452. Introducing first trimester screening for chromosomal
abnormalities in Estonia
K. Muru1,2 , T. Reimand1 , M. Sitska1 ;
1 2 Medical Genetics Center, Tartu University Clinics, Tartu, Estonia, Institute of
General and Molecular Pathology, University of Tartu, Tartu, Estonia.
Prenatal diagnosis of genetic disorders in Estonia has been offered
since 1990. Second trimester maternal serum screening was started in
1998. In 2001 first trimester ultrasound screening (NT) was introduced
in some centers. Since February 2005 the combined first trimester
screening (serum screening+NT) is offered in Tartu University Clinics.
Our study included 1275 women at the first trimester of pregnancy.
In 10 +1 - 13 +6 week of pregnancy PAPP-A and free ß-HCG were measured.
Eighty-five percent of women underwent the combined 1st trimester
screening (NT + PAPP-A and free ß-HCG). For individual risk
calculation we used Prisca 4.0 software (distributed by Siemens Medical
Solutions Diagnostics). All women had also 2nd trimester routine
ultrasound screening in 19-20 week of pregnancy.
First 500 women underwent also routine 2nd trimester serum screening.
From the beginning of 2006 stepwise sequential screening was
developed for 1st and 2nd trimester screening. Screening positive (risk
for trisomy 21 of ≥1: 270 at term) were 10,2% of tests based only
on biochemical markers and 4,6% of combined screening tests. Eight
women fulfilled criteria (risk for DS >1:50 and NT >2,5 mm or NT >3,0
mm) for early invasive diagnostics test (CVS). Chromosomal analysis
(via CVS or AC) revealed 4 Down syndrome, 1 Edwards syndrome and
1 triploidy (69,XXX). During study period were found 2 “false negative”
Down syndrome cases. The essential criteria for using 1st trimester
screening wider in Estonia is the feasibility to measure NT during 12-
13. week of pregnancy, which is now possible only in few centers.
P0453. Assessment of the Fragile X PCR assay in routine
diagnostic practice
Z. Musova, S. Bendova, K. Pavlikova, P. Hedvicakova, A. Krepelova;
Department of Biology and Medical Genetics, Charles University - Faculty Hospital
Motol, Prague, Czech Republic.
Here we present our initial assessment of the Fragile X PCR kit (Abbott)
in diagnostic practice. Sample genotype was determined using an
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