2009 Vienna - European Society of Human Genetics

Clinical genetics and Dysmorphology
and research scientists to assess training needs. Furthermore, we
have also developed courses in biobanking which are emerging as
important resources for translating knowledge of the human genome
into real benefits for health.
Courses launched in 2007 for clinical cytogeneticists and genetic counsellors
have become well-established, receiving excellent appraisal
from both delegate and professional bodies alike. The reputation of
our courses in bioinformatics for cytogeneticists and molecular geneticists
has led to them being repeatedly over-subscribed. More recent
courses in Real-Time PCR and biobanking have attracted delegates
from around the world and in 2009 we are launching courses in micro
RNA analysis and array CGH.
To date, over 400 genetics professionals have attended our courses.
These are part of a broader training programme at Nowgen that has
attracted over 1,500 delegates in the past 5 years. We will continue to
monitor emerging training needs of research and clinical scientists, to
update existing courses and to develop fresh initiatives.
P02. clinical genetics and Dysmorphology
P02.001
3-m syndrome: A report of three Egyptian cases
A. M. Ashour, S. A. Temtamy, M. S. Aglan;
National Research Centre, Clinical Genetics Dept., Cairo, Egypt.
The 3-M syndrome is a rare autosomal recessive disorder. It is characterized
by prenatal and postnatal growth retardation associated with
characteristic features. We report on three patients from two unrelated
families, including two male sibs, with the characteristic features and
radiological findings of the 3-M syndrome. The main features in our
cases were low birth weight, short stature, malar hypoplasia, prominent
premaxilla, anteverted nostrils with a fleshy nasal tip, long philtrum,
thick patulous lips, high arched palate, pointed full chin, short
broad neck, broad chest with transverse grooves of anterior thorax,
hyperlordosis, brachydactyly of hands and feet and prominent heels.
Radiographic studies showed slender long bones and ribs, a narrow
pelvis and foreshortened vertebral bodies. Our reported cases are the
offspring of healthy consanguineous parents confirming the autosomal
recessive pattern of inheritance in the syndrome. These are the first
reported Egyptian patients with this rare disorder.
P02.002
Parental origin and distinct mechanism of formation of the
48,XXYY karyotype, molecular characterization
R. Rodríguez-López, M. Núñez, J. Sáenz, C. Corral, E. Sánchez-Gutiérrez, P.
Méndez, M. Garcia de Cáceres, T. Herrera, M. González-Carpio, E. Doblaré, J.
M. Carbonell;
Extremeño Health System, Badajoz, Spain.
Among sex chromosomal aneuploidies, the addition of more than one
extra X and/or Y chromosome are less frequent. We report a child
with karyotype 48,XXYY. Molecular analyses are essential in order
to determine the parental origin and mode of formation of the additional
chromosomes. Quantitative fluorescent PCR (QF-PCR) was
used including the amplification of amelogenin, which is present on
both sex chromosomes in a biallelic form, SRY gene, a polymorphic
short tandem repeat (STR) on the pseudoautosomal region of X and
Y (X22), five polymorphic X-specific STRs, and a Y-specific marker
(G10_STS47). Molecular investigations were compatible with the described
48,XXYY karyotype. Ratio 2:1 corresponding to the peaks in
the detected fluorescence signal of the X22 marker revealed the existence
of the 47,XYY syndrome in the father (Karyotype pending).
Molecular investigations of X STR markers indicated paternal origin of
the additional X chromosome and, consequently an error in paternal
meiosis I.
The QF-PCR technique resulted extremely sensitive to detect X chromosome
anomalies also in postnatal diagnosis and evidenced an infrequent
parental/meiotic origin of the 48,XXYY syndrome. Additional
evidence came from molecular data and gained increased importance
in this variant of Klinefelter’s syndrome, in which distinct patterns of Xinactivation
could play a role in the observed differences in the degree
of clinical manifestations of patients.
Molecular and cytogenetic characterization
PATIENT FATHER MOTHER
KARYOTYPE 48,XXYY XYY (QF-PCR) XX (QF-PCR)
AMEL (Xp22.31-Xp22.1/Yp11.2) XY XY X
SRY (Yp11.31) PRESENT PRESENT NO
X22 (Xq28Yq) 199/225/241pb(2:1:1) 199/225pb(2:1) 220/241pb
DXS6854 (Xq26.1) 110/110pb 110pb 106/110pb
XHPRT (X26.1) 274/285pb 285pb 274/281pb
DXS6803 (Xq21.31) 110/120pb 110pb 120/120pb
DXS8377 (Xq28) 250/262pb 250pb 253/262pb
DXS6809 (Xq21.33) 263/271pb 263pb 267/271pb
G10_STS47 (Yq11.222) PRESENT PRESENT NO
P02.003
A review of congenital abdominal wall defects
E. S. Boia, R. Colta, C. Popescu, C. M. Popoiu, M. Boia;
University of Medicine &Pharmacy, Timisoara, Romania.
Aim: The pathology of umbilical region- middle celosomies-have different
embryology, clinical aspects, treatment and outcomes.Middle
celosomies still represent a significant cause of morbidity and mortality
in neonates.
Material and methods: This is a 9 years period retrospective review of
patients whom were presented to the Pediatric Surgery Department
with gastroschisis, omphalocele and umbilical hernia. Patient’s personal
data, positive diagnosis, presence of other congenital malformations
and outcomes were recorded.
Main results: There were 72 patients (12 presented omphalocele, 24
gastroschisis and 36 umbilical hernia).The omphalocele and gastroschisis
were more often observed to boys ( 58.33%) and umbilical hernia
was more to girls (61,11%). Omphalocele type I Aitken occurred
to 9 cases, type II to 3 cases,embrionar gastroschisis occurred to 15
patients and fetal gastroschisis to 9 cases.Other congenital malformations
( digestive- 12, cardiac and vascular anomalies-7, genitor-urinary-2,
lungs-1 and locomotors anomalies-8) were presented in omphalocele
and gastroschisis and no one in umbilical hernia.Pre-term
neonates were more often in gastroschisis (18 cases -81.82% ) then
to gastroschisis ( 4 cases -18.18%).Surgical treatment was applied in
all cases. Mortality was 16 percents in gastroschisis and zero in omphalocele
and umbilical hernia.
Conclusions: Middle celosomies have requested surgical treatment.
Outcomes are different according to stage of illness, gestational age
and other anomalies associated. Total parentheral nutrition in postoperative
period in gastroschisis and ompalocele increased the prognostic.
P02.004
Array-cGH analysis in a patient with Acrocallosal syndrome
E. F. Belligni1 , G. B. Ferrero1 , A. Vetro2 , N. Chiesa1 , E. Biamino1 , C. Molinatto1 ,
G. Baldassarre1 , O. Zuffardi2 , M. Silengo1 ;
1 2 Department of Pediatrics, University of Torino, Torino, Italy, University of Pavia,
Pavia, Italy.
We present a patient aged 3 years with a clinical diagnosis of acrocallosal
syndrome (ACS) and a complex chromosomal rearrangement
(CCR). Pregnancy was unremarkable, except for the detection of corpus
callosum agenesis in the second trimester. At birth, weight, length,
OFC and Apgar scores were all within normal limits. Severe hypotonia,
hypertelorism, strabismus and nystagmus, short philtrum, micrognathia,
broad thumbs and toes associated with absence of intermediate
and distal phalanges of fifth finger, talipes varus and micropenis were
noted. Abdominal ultrasound examination detected bilateral kidney
malrotation and bilateral vescico-ureteral reflux. Agenesis of corpus
callosum was subsequently confirmed by cerebral MRI. Karyotype
was 46,XY; Prader-Willi syndrome and mithocondrial disorders were
ruled out. A complex chromosomal rearrangement consisting with a
deletion (12)(p12.2p2.1) and a duplication (16)(q23.3) was detected
by a-CGH analysis. Interestingly, the deletion and the duplication have
been inherited from the phenotypically normal mother and father respectively
and they are not described as polymorphic variants. The
CCR detected in our patient has never been associated with ACS, but
being inherited by phenotypically normal parents, its pathogenetic role
is not clear and it is open to speculation.