2009 Vienna - European Society of Human Genetics

Prenatal and perinatal genetics
P05.03
Application of genome wide 250k sNP array analysis in prenatal
diagnosis
B. Faas, I. van de B, A. J. A. Kooper, R. Pfundt, A. P. T. Smits, N. de Leeuw;
Radboud University Medical Centre Nijmegen, Nijmegen, The Netherlands.
Objectives: We explore the possibilities for the application of the Affymetrix
250k SNP array platform in prenatal diagnosis.
Patients/methods: 250k NspI SNP array analyses were carried out on
DNA from 16 fetuses (after TOP; n=11 or IUFD; n=5) and 3 newborns,
all prenatally karyotyped because of ultrasound anomalies and issued
as normal (n=18) or as carrier of a de novo translocation (n=1). CNVs
(gains>200kb and losses>150kb) were categorized as either benign or
(possibly) clinically significant.
Results: Aberrations were detected in 6 cases. Three were highly likely
clinically relevant and cytogenetically not visible: a de novo 2.9 Mb
loss in 17p13 (IUFD), a 5 Mb loss in 3q26.33q27.2 (TOP; de novo
t(3;18)(q26.2;q21.3)) and a maternal UPD 16 (live born child with
MCA). In a fourth fetus a CNV with (yet) unknown clinical significance
was detected: a 340 kb gain in 17q12 (TOP; no parental analysis so
far). Furthermore, in a case of IUFD with no fetal karyotyping possible
and mother being carrier of a t(4;22)(q12;q11.1), a 56.5 Mb gain
of 4p16.3q12 was found. In a newborn with MCA, a 22qter deletion
detected postnatally was further characterized and shown to be 6.1
Mb in size.
Conclusion: In 6/19 cases, genome-wide SNP array analysis enabled
the detection of imbalances that otherwise would have remained undetected.
Its high resolution increases the reliability for detecting imbalances,
but more knowledge is essential to improve the interpretation of
CNVs. Moreover, criteria need to be established for the conscientious
application of prenatal genome-wide array analysis.
P05.04
Prenatal diagnostic of Anomaly Dandy-Walker.
I. V. Soprunova1 , N. V. Tkacheva2 ;
1Astrakhan Medico-Genetic Consulting Centre, Astrakhan, Russian Federation,
2Astrakhan Medical Academy, Astrakhan, Russian Federation.
Dandy-Walker malformation is characterized by agenesis or hypoplasia
of the cerebellar vermis, cystic dilatation of the fourth ventricle and
enlargement of the posterior fossa.
Between 2000 and 2008 the Astrakhan Medico-Genetic Consulting
Centre performed prenatal ultrasound diagnosis for 58220 women.
It was found that 10 fetuses had the Dandy-Walker malformation. 3
women were diagnosed before 22 weeks of pregnancy and 7 - after
22.
4 fetuses were male, 6 were female.
For 7 of the positive fetuses it was their mother’s first pregnancies, 2
- second and 1 - fourth pregnancy.
The main characteristic used to determine a positive test was an enlargement
of the cisterna magna greater than 10 millimeters, complete
aplasia/hypoplasia of the cerebellar vermis.
5 (50%) of the positive cases had fetuses that had hydrocephalus.
4 (40%) had chromosomal abnormalities: trisomy 18 (2) and mosaic
monosomy X (2). All of the present chromosomal abnormalities were
accompanied by defects within the corresponding patient’s central nervous
system (CNS) (dysgensis of the corpus callosum, hyposplastic
brain hemispheres, polymicrogyria) and other organs (congenital heart
defects, clubfoot and omphalocele). 3 of the cases were accompanied
by porencephaly (2) and microcephaly (1), 1 of the cases had cleft lip
and palate.
One of the positive cases had associated CNS and non-CNS-associated
malformation, other have short rib-polydactyly syndrome type 2.
All of these results were verified through autopsy.
Using this data to analyze the rate of Dandy-Walker syndrome, its was
found to be 0,017 % or 1 in 5822 fetuses.
P05.05
Prenatal diagnosis of a bladder exstrophy, a developmental
pathology or a syndromic association ?
F. M. Nedelea 1 , L. Turculet 1 , L. Popescu 1 , C. Preda 1 , M. Ditu 1 , G. Popescu 1 , V.
Plaiasu 2 , G. Peltecu 1,3 , A. Stana 1,4 ;
1 Clinical Hospital Filantropia, Bucharest, Romania, 2 Institut for Mother and
Child, Alfred Rusescu, Bucharest, Romania, 3 Carol Davila University, Bucha-
rest, Romania, 4 Titu Maiorescu University, Bucharest, Romania.
Bladder exstrophy is caused by incomplete closure of the inferior part
of the anterior abdominal wall. It has an incidence of 1/10000-1/40000
births and is more common in males (2,3M/1F). Separation of pubic
bones, low set umbilicus and abnormal genitalia are associated anomalies.
We present a case of bladder exstrophy who was diagnosed prenataly.
It was reffered to our Prenatal Department at 32 weeks of gestation for
a suspicion of ambigous genitalia.
The child was born prematur, at 36weeks. Because of presence of
some dysmorphic features, like low nasal bridge and micrognatia we
have thought to perform further investigations to estabilish if in this
case is just an development defect or bladder exstrophy is a part of a
syndrome. Those aspects are important for prognosis and management
of the case and also for recurence risk.
P05.06
contribution of three-dimensional computed tomography in
prenatal diagnosis of lethal infantile cortical hyperostosis
(caffey disease)
V. Darmency1 , C. Thauvin-Robinet1,2 , T. Rousseau2 , N. Mejean3 , S. Charra2 , F.
Coron1 , C. Cassini1 , F. Huet1 , M. Le Merrer4 , V. Cormier-Daire4 , N. Laurent2 , P.
Sagot2 , L. Faivre1,2 ;
1Centre de Génétique et Centre de Référence « Anomalies du Développement
et Syndromes Malformatifs »,hopital d’enfants, Dijon, France, 2Centre Pluridisciplinaire
de Diagnostic Prénatal, Maternité, Dijon, France, 3Radiologie Pédiatrique,
Hôpital d’Enfants, Dijon, France, 4Centre de Référence Maladies Rares
« Maladies osseuses constitutionnelles », Hôpital Necker-Enfants Malades,
Paris, France.
Infantile cortical hyperostosis (Caffey disease) is characterized by
acute inflammation of soft tissues and profound alterations of the
shape and structure of the underlying bones, particularly the long
bones, mandible, clavicles or ribs. These manifestations generally appear
during the first month of life, though time of onset varies, and a
severe lethal prenatal form has been reported. The diagnosis of lethal
prenatal Caffey disease is generally made post-mortem since the combination
of two-dimensional ultrasound and antenatal foetal x-rays is
not sufficient to make the diagnosis. Here we describe the contribution
of three-dimensional helical computed tomography (3D-HCT) in the
diagnosis of lethal Caffey disease in a 30 WG pregnant woman, evaluated
for shortened and bowed long bones. Periosteal thickening of the
diaphyses and cortical irregularities were in favour of the lethal form of
infantile cortical hyperostosis. This diagnosis was confirmed by postmortem
x-rays and histological examination after elective termination
of pregnancy. The search for the 3040C→T COL1A1 mutation on DNA
extracted from foetal blood cells was negative. This case report is the
first description of 3D-HCT in lethal Caffey disease. It further emphasize
the value of 3D-HCT as a complementary diagnostic tool in the
prenatal diagnosis of osteochondrodysplasia. This
technique provides 3D images of the abnormal findings more readily,
which could aid in counselling and management of the pregnancy.
P05.07
cell cycle studies of human cytotrophoblast cells in missed
abortion
I. Trofimova1 , S. Mylnikov1 , T. Kuznetzova2 , V. S. Baranov2 ;
1 2 St.Petersburg State University, St.Petersburg, Russian Federation, Ott’s Institute
of Obstetrics & Gynecology, St.Petersburg, Russian Federation.
Abnormal proliferation and differentiation of trophoblast can lead to
functional insufficiency of placenta and developmental destruction of
embryo. Meanwhile available data on proliferative capacity and cell
cycle of cytotrophoblast (CTB) in normal and pathological pregnancies
are inconsistent.
Proliferative capacities of CTB of chorion villi samples (CVS) from
missed and artificial abortions (groups M and A respectively) at 5-8
weeks of gestations were studied. After 24, 48, 72 hours incubation
with BrdU, semi-direct preparations and AO staining the metaphases
with SCD and SCE were registered. Group M included CVS with normal
karyotype (N=4) and with heteroploidy (N=4). Group A included
CVS with normal karyotype (N=6).
In spite on conspicuous interindividual variations attributed to the differences
in mitotic activity and gestation ages, obvious differences
were found. The number of cells with accomplished two S-phases after