2009 Vienna - European Society of Human Genetics

Prenatal and perinatal genetics
in fetuses with FEB, emphases on the prevalence of cystic fibrosis
(CF) and on the carrier rate in that population, and assesses the ability
of ultrasonography to detect CF in utero.
Methods: We reviewed all the consecutive cases of FEB diagnosed in
pregnant women living in Brittany and who were referred for an analysis
of the gene responsible for CF (CFTR) over the period 1992-2007.
Results: Over that period, 289 diagnoses of FEB were recorded. A
pathology was evidenced in 32.2% of the fetuses. Beyond CF (8.0%),
it mainly included digestive tract malformations (7.0%), chromosomal
abnormalities (3.7%), viral infections (3.7%) and cardiac disorders
(2.9%). Regarding CF, we identified 23 CF fetuses and 19 heterozygous
ones, leading respectively to a CF prevalence of 8.0% (1/13) and
a carrier rate of 6.6% (1/15) in fetuses with FEB (rates significantly
higher than in the general population). Moreover, by combining these
data with those of our newborn screening programme, we showed that
ultasonography enabled to diagnose in utero 10.7% of the CF fetuses
over the study period.
Conclusion: This study highlights the importance of ultrasound examinations
of pregnancies and of the diagnosis of FEB, as well as the
efficiency of ultrasonography to detect CF in utero.
P05.41
Walker-Warburg syndrome with hyperplastic primary vitreus
detected by prenatal ultrasonography: case report
F. Yazicioğlu 1 , Z. Ocak 2 ;
1 Perinatology,Süleymaniye Maternity Hospital for Research and Training, zeytinburnu,
Istanbul, Turkey, 2 Medical Genetics,Süleymaniye Maternity Hospital for
Research and Training, zeytinburnu, Istanbul, Turkey.
Walker-Warburg syndrome (WWS) is an autosomal recessive disease
presenting with muscular dystrophy associated with cerebral,
cerebellar and eye anomalies, in which the life span of patients is
short 1 . Following the detection of hydrocephaly during routine USG
for a 28-weeks-pregnant mother, antenatal USG in the perinatalogy
department revealed hydrocephaly along with persistent hyperplastic
primary vitreous (PHPV). A presumptive diagnosis of Walker-Warburg
syndrome was made. The information was used to treat this patient in
her immediate postnatal life. This case, being the second in the literature
with persistent hyperplastic primary vitreus (PHPV) detected by
prenatal USG, demonstrates the importance of antenatal diagnosis in
this condition.
P05.42
sex reversal and growth retardation : two case reports with
partial Xp duplication analyzed by array-cGH
E. LANDAIS1 , F. SCHNEIDER1 , F. CARRE-PIGEON1 , E. ALANIO2 , O.
NOIZET3 , S. AKHAVI3 , C. SOMMER3 , D. GAILLARD1 , M. DOCO-FENZY1 ;
1Service de Génétique, CHRU de Reims, UFR de Médecine, IFR53, EA 3001,
Reims, France, 2Laboratoire Pol Bouin du CHRU de Reims, Reims, France,
3Service de Réanimation Infantile et Pédiatrique du CHRU de Reims, Reims,
France.
Transcription factors such as SRY, SOX9, DAX1, WT1, SF1 and WNT4
are involved in many genital development. Segmental duplication of
the X chromosome can interfere with the testis differentiation in 46,XY
subjects. The Xp region causing sex reversal is designated Dosage
Sensitive Sex reversal and contains the DAX1 gene (Xp21.2).
We report two cases of females with growth retardation, facial dysmorphism,
46,XY karyotype and partial Xp duplication due to autosomal
translocation. Such observations have been rarely reported. In both
cases, Y chromosome and SRY gene were normal as ascertained by
FISH and molecular biology.
Case 1 : cytogenetic analysis was motivated by growth retardation and
hydramnios. Xp disomy was derived from a translocation with the 1
chromosome : 46,XY,der(1)t(1;X)(p36;p21). Fetal postmortem showed
female external and internal genital tract with hypoplastic ovaries and
hypoplastic adrenals. Under microscope, no tunica albuginea could be
seen and the sex cords were dysgenetic. No primordial follicle were
differentiated.
Case 2 : the female infant was born with severe growth retardation and
ambiguous genitalia. She died of meningitis at 18 days of life. A Xp
disomy was detected derived from a translocation with the 14 chromosome
: 46,XY,der(14)t(14;X)(q32;p21).
Array-CGH analysis characterized the length of Xp duplications : 33.88
+/- 1.40Mb and 28.68 +/- 0.25Mb (case 1 and 2 respectively).
According to these results, two copies of DAX1 were present in case 1
and could explain the fetal sex reversion, but there was only one copy
in case 2. Other genes than DAX1 could be implicated.
P05.43
Extreme nephromegaly: an unusual antenatal presentation of
Zellweger syndrome
L. Pinson1 , N. Bigi1 , A. Couture2 , C. Rouleau3 , P. Blanchet1 , F. Deschamps4 , A.
Schneider5 , P. Boulot4 , G. Lefort5 , M. Zabot6 , C. Vianey-Saban6 , P. Sarda1 , D.
Geneviève1 ;
1Service de Génétique Médicale et de Foetopathologie, Hôpital Arnaud de
Villeneuve, Université Montpellier 1, CHRU de Montpellier, Montpellier, France,
2Service de Radiologie Pédiatrique, Hôpital Arnaud de Villeneuve, CHRU de
Montpellier, Montpellier, France, 3Service d’Anatomo-Pathologie, Hôpital Lapeyronie,
CHRU de Montpellier, Montpellier, France, 4Maternité, Hôpital Arnaud de
Villeneuve, CHRU de Montpellier, Montpellier, France, 5Service de Cytogénétique,
Hôpital Arnaud de Villeneuve, CHRU de Montpellier, Montpellier, France,
6Centre de Biologie et de Pathologie Est, hospices Civils de Lyon, Montpellier,
France.
Zellweger syndrome (ZS) is a rare severe autosomal recessive disorder,
characterized by the reduction or absence of peroxisomes in liver,
kidneys, and brain. ZS patients display dysmorphic features, severe
neurological dysfunction, hepatic and renal failure, and rarely survive
their first year.
Because of genetic heterogeneity, ZS diagnosis is usually based on
biochemical investigation characterized by elevated plasma verylong-chain
fatty acids (VLCFA), pipecolate and bile acid intermediates
contrasting with low plasma plasmalogens. Some impaired enzymatic
activity, such as dihydroacetone-phosphate acyltransferase deficiency
(DHAP-AT) can also be detected in fibroblasts of ZS patients.
Here, we report on major and evolutive nephromegaly in a fetus with
ZS. This was the first pregnancy for the healthy unrelated parents.
Isolated nephromegaly (39mm, normal: 26mm) was observed at 22
weeks’gestation (WG). Clinical course was marked by a rapid increase
in kidney size at 28 WG (68mm, normal: 32mm) with multiple cortical
microcysts.
Diagnosis was performed after termination of pregnancy based on
dysmorphic features (high forehead, macroglossia), nephromegaly
without hepatomegaly and stippling of patella and hips.
Neuropathological findings included cortical polymicrogyria, cerebellar
and bulbar heterotopias.
Biochemical investigations confirmed the deficit of the beta-oxydation
of VLCFA and impairment of DHAP-AT enzymatic activity in cultured
amniocytes.
To our knowledge, this is the first report of prenatal evolutive nephromegaly
leading to diagnosis of Zellweger syndrome. We suggest that
ZS should be considered as a possible diagnosis in evolutive nephromegaly.
P05.44
Growth and medical outcome of hundred and two 2-year-old
children conceived after preimplantation genetic diagnosis or
screening
S. Desmyttere, J. De Schepper, I. Liebaers, M. Bonduelle;
UZBrussel, Jette, Belgium.
Objective: In preimplantation genetic diagnosis (PGD) or preimplantation
genetic screening (PGS), embryo biopsy is an invasive essential
procedure. The major objective of this study was to determine if the
embryo biopsy might cause growth restriction and/or affect health outcome
of children.
Study design: In this prospective study, 102 children (70 singletons
and 32 twins) born after PGD/PGS were compared with a matched
group for gender, maternal educational level, mother tongue and birth
order of 102 children (70 singletons and 32 twins) born after intracytoplasmatic
sperm injection (ICSI). Auxological data at birth and 2 years,
physical findings, data on sociodemographic parameters, medical history
of the pregnancy and the child were compared for both groups.
Results: No statistically significant differences regarding weight, height
and head circumference standard deviation scores (SDS) at birth and
at age two years were observed. At two years of age the mean body
mass index SDS tended to be lower in PGD/PGS children (p=0.058).
PGD/PGS babies had been more often breastfed (p=0.013), but mostly
during a shorter time.