2008 Barcelona - European Society of Human Genetics

Prenental diagnostics
etal anomalies (thin ribs, hypoplastic clavicules) and lung hypoplasia .
We report prenatal ultrasound findings and molecular genetic diagnosis
of this disorder in a woman whose first child died a few hours after
birth . From clinical appearance restrictive dermopathy was suspected .
There was distant consanguinity of the parents .
Ultrasound examinations in the 29 th week of a further pregnancy showed
growth retardation, short extremities, reduced fetal movements
and abnormal shrunken amnion membranes. Additional findings of absent
clavicules, thin ribs, an abnormal face with small nose and open
mouth strongly suggested the diagnosis of restrictive dermopathy . The
shrunken and separated amnion membranes seem to be recorded for
the first time in restrictive dermopathy. The child was born in the 32 nd
week of gestation after premature rupture of membranes and died 30
minutes after birth . It showed the expected facial anomalies, a very
tight translucent skin with venal pattern and contractures . Morphology
of the skin revealed typical findings in restrictive dermopathy with absent
rete ridges of the epidermis, hypoplastic appendage structures,
very thin dermis and rarefied elastic fibres.
The assumed diagnosis of restrictive dermopathy was confirmed by
molecular genetic analysis . A homozygous mutation c .1085-1086insT
in the ZMPSTE24 gene was detected . In the following still ongoing
pregnancy early molecular genetic prenatal diagnosis could be offered
after chorionic villi biopsy resulting in an unaffected fetus .
P03.73
Fraser syndrome in two Fetuses: clinical, Radiological And
Pathological Evaluation
F. Ekici, O. Sezer, M. Tosun, F. Karagoz, M. Ceyhan, B. Ozyilmaz, M. Ture, E.
Malatyalioglu, G. Ogur;
Ondokuz Mayis University Medical Faculty, Samsun, Turkey.
Fraser syndrome (FS;OMIM 219000) is an extremely rare autosomal
recessive disorder characterized by cryptophthalmos, cutanaeous syndactyly,
ambiguous genitalia, laryngeal/genitourinary malformations,
craniofacial dysmorphism and mental retardation . Here, we present
two fetuses with FS diagnosed after termination of pregnancy because
of severe fetal abnormalites .
Case1: At the 18th week a cordocentesis was performed to the first
pregnancy of a consanguinous 26 year-old father and 21 year-old
mother because of intraabdominal ascites, unilateral renal agenesis,
and cystic adenomatoid malformation of lung (type3)[CCAML3] . Fetal
karyotype was 46,XY . After genetic counselling, parents decided to terminate
the pregnancy . Fetus presented bilateral cryptopthalmos, hypertelorism,
ear/nose anomalies, tetramelic cutaneous syndactyly, single
artery/vein, small penis, and scrotal hypoplasia . Autopsy revealed
unilateral right renal agenesis, left renal dysgenesis but no CCAML3 .
Case2: Amniocentesis for was performed at 25 +3 th week of gestation of
a 29 year-old father and 26 year-old mother because of ultrasound abnormalities:intraabdominal
ascites, bilateral renal agenesis, CCAML3,
oligo-anhydramnios, nuchal edema, intracardiac hyperechogenic focus,
hyperechogenic bowel . Parents were consanguinous . One previous
pregnancy ended spontaneously; another was medically aborted .
Karyotype was 46,XX . Parents decided to terminate the pregnancy .
Fetus showed facial asymmetry, right sided cryptophthalmos, ear/nose
anomalies, tetramelic cutaneous syndactyly, umbilical hernia, anterior
abdominal wall defect, immature external genitalia, and anal atresia .
X-ray revealed 11 ribs. Autopsy confirmed bilateral renal agenesis; gonads
were immature, undifferentiated .
P03.74
Outcome of fetuses with central nervous system anomalies
detected by ultrasound during pregnancy: clinical, cytogenetic,
radiological and pathological data from 18 fetuses
G. Ogur, M. Tosun, Ö. Sezer, M. Ceyhan, T. Alper, F. Ekici, B. Özyılmaz, O.
Aydın, M. Türe, E. Malatyalioglu;
Ondokuz Mayis University Medical Faculty, Samsun, Turkey.
Fetal brain anomalies constitute a heterogeneous group of disorders
with different prognostic outcome . Affected fetuses mostly come to attention
because of ultrasound (US) and often on indication termination
of pregnancy, before 24th of gestation, and with parental consent, occurs
. Here we report outcome of 18 fetuses with brain malformations
initially seen on routine US screening during pregnancy . After termination
of pregnancy a thorough examination of the fetus, followed by
imaging (X-ray, MRI) and autopsy was done .
Out of 18 fetuses 11 were with chromosomal abnormalities(61%):
der(1) (p36,1;p21,3), mosaic trisomy 8, trisomy 18 (two cases), trisomy
21 (one case), 47,XXX, 45, X, 47,XXY, 49,XXXXY, “de novo”
inv(9)(p11q13), and a homozygous inv(6)(p23q23) . Seven patients
presented monogenic syndromes(39%):skeletal dysplasias(3 cases:
Short-Rib Polydactyly Saldino-Noonan Type, Thanotophoric Dysplasia
San Diego Type and Jarcho-Levin syndrome), alobar holoprosencephaly(2
cases), iniencephaly(one case), Dandy-Walker syndrome(one
case) and cranial teratoma (one case) . The fetus with iniencephaly
showed also paracentric inversion of “both” chromosomes 6 . The
parents, both were carriers for inv(6q) . Following clinical diagnosis all
families received genetic counselling and fetal DNAs were isolated for
possible Gene mutation analysis .
We believe that management of fetal malformations is an extensive,
heavy “team work” yet the best way of structuring bases for phenotype-genotype
correlations .
P03.75
congenital lamellar ichthyosis: tGm1 gene mutation analysis
and prenatal diagnosis of a twin pregnancy
B. Ozyilmaz1 , M. Tosun1 , B. Demir1 , C. Goktas1 , T. Oztas1 , S. Bale2 , G. Ogur1 ;
1 2 Ondokuz Mayis University Medical Faculty, Samsun, Turkey, GeneDx, Gaithersburg,
MD, United States.
Autosomal recessive congenital ichthyosis include several subtypes:
lamellar ichthyosis, Harlequin ichthyosis and non-bullous congenital
ichthyosiform erythroderma . Differential diagnosis of these subtypes
can be obtained with strict clinical criteria which is crutial for gene-mutation
selection . In this report we present prenatal diagnosis of “Congenital
Lamellar Ichthyosis” of a mother with twin pregnancy whose
previous child was diagnosed with lamellar ichthyosis .
The previous affected child had a history of erythroderma and ectropion
since birth . At referral to our center, he presented dry skin with
dark scales over his entire body . Scales were also present over the
cutaneous surfaces of flexural accentuation . Hyperkeratotic fissures
covering palms and soles of the hands and feet were remarkable . Facial
skin under eye level was intact and eyelids exibited mild ectropion .
The patient had no other medical problems, and his growth and development
have been normal .
TGM1 gene analysis of the index patient showed homozygous mutation
at Exon 5, G278R . Amniocentesis was performed for biamniotic
twin pregnacy . TGM1 gene analysis revealed heterozygous TGM1
Exon 5 G278R mutations in both fetuses rendering both fetuses being
clinical carriers . Karyotypes of the fetuses were normal . Family
decided to continue the pregnancy . At birth twins were normal .
P03.76
smith-Lemli-Opitz syndrome, Prenatal Biochemical and
molecular Diagnosis
B. Özyılmaz 1 , G. Celep 1 , L. E. Kratz 2 , M. Witsch-Baumgartner 3 , G. Ogur 1 ;
1 Ondokuz Mayis University Medical Faculty, Samsun, Turkey, 2 Kennedy Krieger
Institute, Baltimore, MD, United States, 3 Department of Medical Genetics, Mol.
Clin. Pharmacology, Innsbruck, Austria.
Introduction: Smith-Lemli-Opitz Syndrome is an autosomal recessive
disorder presented with clinical hallmarks like characteristic facial phenotype,
cleft palate, thumb-toe abnormalities and ambiguous genitalia .
Prenatal and postnatal diagnosis is possible by the detection of low
cholesterol and high 7DHC levels in both serum and amniotic fluid. In
this report we present a 40 day-old baby diagnosed SLOS Type 1 and
prenatal diagnosis in the family’s subsequent pregnancy .
Case Presentation: The case presented with growth retardation, cleft
palate, facial dysmorphism, unilateral oligodactyly, unilateral congenital
cataract and ambiguous genitalia . Biochemical parameters showed
low serum cholesterol and high serum 7DHC levels . The child was diagnosed
as SLOS . Due to family’s demand, prenatal diagnosis during
the subsequent pregnancy was performed; the parents were checked
for DHCR7 gene mutations . c.384-IVS5+4del and p.S397L mutations
were found to be heterozygous in the mother and father respectively .
c.384-IVS5+4del is a previously unidentified mutation for SLOS.
An amniocentesis was performed at 16th week of gestation . Amniotic
fluid showed normal levels of 7-Dehydrocholesterol and molecular
analysis revealed normal DNA results . Cytogenetic analysis revealed
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