2008 Barcelona - European Society of Human Genetics

Prenental diagnostics
To date, follow-up failed to reveal abnormality on physical or psychomotor
development at 1 month or at 1,12,18 months, respectively .
P03.68
Prenatally detected trisomy 7 mosaicism in a child with
Blaschlolinear skin pigmentary variation and developmental
delay.
M. Mori1 , F. Santos1 , A. Díaz de Bustamante2 , M. Palomares1 , L. Fernández1 ,
M. Muñoz3 , P. Lapunzina1 ;
1Department of Medical Genetics, Hospital Universitario La Paz, Madrid, Spain,
2 3 Department of Medical Genetics, Hospital de Móstoles, Madrid, Spain, Department
of Paediatrics, Hospital de Fuenlabrada, Madrid, Spain.
We report on a girl showing Blaschkolinear skin pigmentary variation
associated with developmental delay and minimal facial dimorphisms .
The proband´s mother was referred for prenatal diagnosis at week 15
of gestation, due to nuchal translucency of 3 .5 mm and unique umbilical
artery . A chromosomal analysis was performed in cultured amniocytes
in two consecutive studies, both showing 46, XX [40%] / 47,
XX,+7 [60%] . A study in fetal blood lymphocytes excluded uniparental
disomy 7 by microsatellites analysis, and revealed a normal karyotype
(46 XX) . During pregnancy only intrauterine growth delay was noted .
At 45 days of age, the patient was evaluated not disclosing any clinical
anomaly and the chromosomal analyses were repeated revealing
the previous results . The proband was periodically evaluated showing
a progressive developmental delay . In the last review, at 22 months
of age, Blaschkolinear skin pigmentation anomalies were detected in
both lower extremities and thorax associated with sparse hair, abnormal
dentition and a moderate developmental delay . This brings up the
possibility that the mosaic trisomy 7 line should still be present in skin
cells and it could be present in any other tissue .
When a mosaic trisomy 7 is diagnosed prenatally in cultured amniocytes,
and it is not confirmed in a fetal lymphocyte karyotype, it is
essential to follow up these patients postnatally to establish an early
physical, occupational and language therapy in order to improve their
developmental outcome . Absence of pigmentary alterations along
Blaschko lines at birth is not exclusive, as they could appear any time
during childhood .
P03.69
Foetal ultrasound findings in trisomy 18
A. Ljubic1 , B. Petrovic1 , J. Joksimovic2 ;
1 2 Institute for gynecology and obstetrics, Belgrade, Serbia, Medicines and medical
devices agency of Serbia, Belgrade, Serbia.
Among liveborn children, trisomy 18 is the second most common autosomal
trisomy after trisomy 21 . The disorder/condition is caracterised
by severe psychomotor and growth retardation, microcephaly, microphthalmia,
malformed ears, micrognathia or retrognathia, microstomia,
distinctively clenched fingers, and other congenital malformations.
Approximately 95% of conceptuses with trisomy 18 die in embryonic or
foetal life; 5-10% affected children survive beyond the first year of life.
The aim of this study was to estimate the correlation between pathological
foetal ultrasound findings and trisomy 18.
Over the past five years (2003-2008) we analyzed fetal blood samples
for chromosome abnormalities . Samples were taken by cordocentesis
and processed using standard techniques . All specimens were Gbanded
using trypsin-Giemsa . Sixteen metaphase cells were analyzed
for chromosomal constitution in each sample .
From 1248 samples of fetal blood analyzed for chromosomal abnormalities,
there were 11 (0,88%) with complete trisomy 18 . We found no
mosaicism, or partial trisomy 18 . From 11 fetuses with trisomy 18, 9
(81,8%) had some anomaly detected by ultrasound. Ultrasound findings
were polyhydramnion, IUGR, oligohydramnion, heart defect, hydrocephalus
and omphalocele .
In the last 5 years in our laboratory, the incidence of trisomy 18 was
0,9% . In all cases, trisomy 18 was complete . About 81% of the fetuses
with trisomy 18 had ultrasonographically detected anomalies .
P03.70
stRs multiplex assay for rapid and economic detection of UPD
15
R. Cascella 1 , C. Peconi 1 , C. Sinibaldi 1 , E. Giardina 1 , A. Nardone 1 , G. Novelli 1,2,3 ;
1 Department of Biopathology and Centre of Excellence for Genomic risk Assessment
in Multifactorial and Complex Diseases, School of Medicine, Uni-
versity of Rome “Tor Vergata”, Rome, Italy, 2 Department of Cardiovascular
Medicine, University of Arkansas for Medical Sciences,, Little Rock, AR, United
States, 3 Fondazione Livio Patrizi, Rome, Italy.
Uniparental disomy (UPD) describes the inheritance of both homologues
of a pair of chromosomes from only one parent . The clinical
impact of UPD and associated imprinting disorders, such as Prader-
Willi syndrome (PWS) and Angelman syndrome (AS) increasingly
have come to our attention . Chromosome 15 UPD testing is also relevant
in various prenatal diagnostic conditions including apparent confined
placental mosaicism (CPM), homologous and nonhomologous
Robertsonian translocations involving chromosome 15 and 14, and as
genomic biomarker for detecting chromosome origin . We developed
and validated a two fluorescent STR multiplex assays for a rapid and
economic detection of UPD 15 by capillary electrophoresis . Eight informative
markers have been selected on the basis of their expected heterozygosity
and chromosomal localization . We developed two different
four-plex PCRs: multiplex 1 containing microsatellites D15S1007,
D15S205, D15S1019 and D15S130; multiplex 2 containing markers
D15S988, D15S979, D15S128 and D15S131 . In order to assess and
validate the polymorphic information content (PIC), allele frequencies
and heterozygosity of selected markers we typed 100 unrelated individuals
. Statistical analysis revealed a probability to obtain an informative
assay of 99 .1% for multiplex 1 and 98 .8% for multiplex 2 . Genotyping
results of the two four-plexes were compared with those generated
in singleplex reactions for the same samples revealing a concordance
rate of 100%. To summarize, UPD exclusion/confirmation is expected
to be needed in an increasing number of cytogenetic and clinical cases
and we believe that the availability of a rapid test for its recognition
should be highly suitable by both genetic laboratories .
P03.71
Mild/borderline ventriculomegaly as a marker for structural
chromosome abnormalities
K. Writzl 1 , A. Veble 1 , M. Volk 1 , V. Cerar 2 , B. Šajina Stritar 2 , S. Pušenjak 2 , B.
Peterlin 1 ;
1 Institute of Medical Genetics, UMC Ljubljana, Ljubljana, Slovenia, 2 Perinatology
Unit, Department of Obstetrics and Gynecology, UMC Ljubljana, Ljubljana,
Slovenia.
Ventriculomegaly is a descriptive term for enlargement of the intracranial
ventricular system. It is defined as a ventricular atrium at any
gestation, which measures 11 mm or greater . The frequency of chromosomal
anomalies reported in the literature in fetuses with ventriculomegaly
ranges from 3 to 27% . Separate analysis for mild and moderate
ventriculomegaly is not carried out .
We report two prenatal cases with mild ventriculomegaly and structural
chromosome abnormalities .
Case 1: prenatal ultrasound at 21 weeks of gestation noted the fetus
to have mild ventriculomegaly (Vhposterior = 11 mm) . Chromosome
analysis following amniocentesis demonstrated a 1p36 deletion, which
was confirmed by fluorescence in situ hybridization (FISH). Subsequent
analysis revealed an unbalanced translocation between 1p and
10q resulting in 1p36 .1->pter deletion and 10q26 .3->qter duplication .
Case 2: at 21 weeks of gestation mild ventriculomegaly (Vhposterior
= 11 mm) and intracardiac hyperechogenic focus were detected .
Cytogenetic analysis of cultured amniocytes revealed an inverted
duplication of the short arm of chromosome 9 . The karyotype was:
46,XY,dup(9)(p13p24) . In both cases parents opted for termination of
pregnancy .
We conclude that borderline ventriculomegaly may occur in association
with structural chromosomal abnormalities, and propose that
karyotype is offered and FISH analysis is done where a cryptic rearrangement
is suspected following classical G-banding techniques .
P03.72
Prenatal diagnosis of restrictive dermopathy
C. Daumer-Haas 1 , L. T. T. Huong 2 , N. T. Duong 2 , I. Hausser 3 , M. Wehnert 2 , K.
P. Gloning 1 ;
1 Pränatal-Medizin München, Munich, Germany, 2 Institut für Humangenetik,
Greifswald, Germany, 3 Dermatologische Klinik, Universität, Heidelberg, Germany.
Restrictive dermopathy (OMIM 275210 ) is a rare lethal autosomal recessive
disorder characterized by rigid skin, facial dysmorphism (hypertelorism,
small nose, open mouth) , multiple joint contractures, skel-