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

Prenatal diagnosis
P0462. Increased Nuchal Translucency as a Prenatal Marker in
Wolf-Hirshhorn Syndrome.
A. Singer 1 , S. Josefsberg 2 , C. Vinkler 3 ;
1 Genetic Institute, Ashkelon, Israel, 2 Institute of Clinical Genetics, Kaplan Medical
center Rehovot, Israel, 3 Institute of Medical Genetics, Wolfson Medical
Center Holon, Israel.
Wolf-Hirschhorn syndrome is characterized by multiple congenital
anomalies.
The syndrome is caused by partial aneupleoidy of the short arm of
chromosome 4.
Patients are characterized by microcephaly, hypotonia, mental retardation,
cardiac anomalies, club feet and characteristic dysmorphic facial
features with cleft lip and palate, micrognathia, hypertelorism and
midline defects.
Routine ultrasound imaging during second and third trimester pregnancy
detects IUGR as well as most of the anomalies associated with
Wolf-Hirschhorn syndrome. However, increased nuchal translucency
(NT) has not been frequently described previously in this syndrome.
We present two young women who were referred to the genetic unit
between 12 and 13 weeks gestation due to increased NT. Chromosomal
analysis in both cases,
revealed deletion of the short arm of chromosome 4. In the first case
hydrops developed and the women decided to terminate the pregnancy.
In the second case early ultrasound screening at 15 weeks gestation,
demonstrated multiple anomalies
and later there was fetal demise.
Increased nuchal translucency as a presenting symptom, has been
previously described in relation with common chromosomal aneuploidies.
Only rarely is it associated with other types of chromosome
abnormalities. Our cases provide further evidence of a possible relationship
between increased nuchal translucency and a chromosomal
deletion syndrome.
P0463. Two prenatal cases of Pallister-Killian syndrome
V. Krutilkova1 , E. Hlavova1 , M. Trkova1 , M. Louckova1 , J. Sehnalova1 , N. Jencikova1
, Z. Zemanova2 , K. Michalova2 ;
1 2 Institute of Medical Genetics, Praque 7, Czech Republic, Center of Oncocytogenetics
UKBLD, General Faculty Hospital, Praque 2, Czech Republic.
Pallister-Killian syndrome (PKS) is a rare sporadic syndrome. PKS is
caused by a tissue-specific mosaicism distribution of supernumery isochromosome
12p.
Clinical findings in PKS include congenital defects (diafragmatic hernia,
micromelia, hydramnios), mental retardation, seisures, streaks
hypo or hyperpigmantation, facial dysmorphism.
We report two prenatal cases which illustrate the great variability of
the tissue-specific mosaicism distribution. Both mothers were over 35
years old.
Case 1: Sonographic investigation showed nuchal translucency (NT)
2,6mm, ventricular dilatation, flat faces, micromelia. The section described
diafragmatic hernia, low-set ears, hydrocephalus too. Tetrasomy
12p was found in 67% amniotic fluid cells and in 6% fetal blood
cells.
Case 2: The socond trimestral screening test was positive, sonographic
examination showed diafragmatic hernia. Tetrasomy 12p was found
in 13% amniotic fluid cells, in 48% fetal blood cells and in 45% skin
fibroblasts.
The cytogenetic investigation performed the diagnosis of PKS in both
our cases by amniocentesis. M-FISH and mBAND analysis confirmed
identification of isochromosome 12p, resp. i(12)(p10).
We discuss the difficulties of prenatal diagnosis due the variability of
the tissue-specific distribution mosaicism and due the variability of the
fetal phenotype.
The false negative results of PKS were reported on amniocentesis, on
CVS but most often on fetal blood sample.
P0464. Verification of an improved strategy for combined first
trimester screening and of commercial PAPP-A/proMBP complex
examination for early detection of acute coronary disease
M. Macek Sr. 1 , P. Hajek 2 , P. Ostadal 3 , A. Lashkevich 1 , D. Chudoba 1 , H. Kluckova
1 , M. Simandlova 1 , R. Vlk 4 , I. Spalova 4 , M. Turnovec 1 , J. Diblík 1 , M. Havlovicova
1 , M. Macek Jr. 1 ;
1 Department of Biology and Medical Genetics, Charles University - Faculty
Hospital Motol, Prague, Czech Republic, 2 Department of Internal Medicine,
Charles University - Faculty Hospital Motol, Prague, Czech Republic, 3 3rd Department
of Internal Medicine, Charles University - Faculty Hospital Kral. Vinohrady,
Prague, Czech Republic, 4 Department of Obstetrics and Gynecology,
Charles University - Faculty Hospital Motol, Prague, Czech Republic.
Here we report verification of screening efficacy, complemented by
aneuploidy risk evaluation, based on the degree of PAPP-A/proMBP
and β-hCG deviations, including assessment of PAPP-A/proMBP
complex as a biomarker of acute coronary disease (ACD). Analytes
were examined in 2702 sera by Kryptor system/assays (Brahms), with
trisomy 21/18 ascertainment by Lifecycle/Elipse software (Perkin-Elmer).
Aneuploidy risk was evaluated according to analyte MoMs and
NT deviations in 4 categories: I.: 0.6-1.9, II.: 0.5-0.59 and 1.91-2.0,
III.: 1 analyte 2.0, IV.: both analytes 2.0. PAPP-A/
proMBP Kryptor kit was used for sera examination in 51 controls, 110
stable coronary disease and 258 unstable angina pectoris (UAP) and
STEMI and NSTEMI myocardial infarction cases. No autosomal or heterochromosomal
aneuploidies were found in cat. I. Frequency of autosomal
aneuploidies gradually increased from II. to IV. with the highest
prevalence in cat. IV. Heterochromosomal aneuploidies were higher in
cat. II. versus III./IV. These were detectable by analyte deviations only,
whereas autosomal aneuploidies by increased NT, analyte deviation
and software risk determination. Thus far, no case of fetal aneuploidy
was missed by this strategy. Data from screening questionnaires enabled
indication of counselling in 25% woman in cat. I. for improvement
prenatal care because of other genetic, obstetric or exogenic
risk factors. PAPP-A/proMBP examination proved, that serum levels
were significantly increased only in UAP and myocardial infarctions
(p