2008 Barcelona - European Society of Human Genetics

Clinical genetics
P01.270
Genetic study of chromosome 5 aberrations
L. A. Hosny, S. Hammad, M. Shihab;
National Research Centre, Cairo, Egypt.
This work presents clinical picture of 12 cases having chromosome 5
aberrations .
Material & Methods:- 6 children, a couple seeking premarietal genetic
counselling and 5 couples seeking advice for, intrauterine and neonatal
deaths .Chromosomal study of the children, their parents and the
couples was per formed
Results & discussion: 5p- in 4 children diagnosed as cri du chat
syndrome,three with normal karyotype of both parents . in the
fourth child , the mother was a balanced translocation carrier
t(5;22)(P14;P11 .2) , sister was unbalanced carrier t(5;22)(P14;P11 .2)
, 5p+ and the aunt had 5p- . Fifth child had 46 , xy , del (5)P15 .2 , inv
(9)(P11;q12) showing features of both cri du chat and Goldenhar syndromes
. The sixth child had 5p+ and his father was a balanced translocation
carrier t(3;5)(P22;P15) . 5 paracentric inversion was found in
the mother in a couple ,the other 5 couples showed chromosome 5
balanced translocation .
In one couple, the father was a balanced carrier t(5;7)(P15;P15) having
a normal son with a balanced translocation and daughter with
multiple congenital anomalies and a normal karyotype . The present
study illustrates that chromosome 5 inversion or balanced translocation
in one of the parents results in chromosome 5 aberrations in the
offspring leading to intrauterine and neonatal deaths as well as genetic
syndromes .
CONCLUSION:-Cytogenetic study of parents of children with chromosome
5 aberrations , couples seeking premarietal genetic counseling
or having repeated abortions, intrauterine and neonatal deaths is of
considerable value to give a proper genetic counseling for next generations
.
P01.271
Expanding the mutational spectrum of cRLF1 in crisponi
syndrome.
L. Crisponi1 , A. Meloni1 , F. Chiappe1,2 , G. Zampino3 , I. Okur4 , S. Danda5 , G.
Crisponi6 , F. Rutsch7 ;
1Istituto di Neurogenetica e Neurofarmacologia, Consiglio Nazionale delle
Ricerche, Monserrato, Italy, 2Università degli Studi di Cagliari, Cagliari, Italy,
3 4 Departments of Paediatrics, Catholic University, Rome, Italy, Gazi University
Medical School, Department of Pediatric Nutrition and Metabolism, Ankara,
Turkey, 5Clinical Genetics Unit, Department of Gastrointestinal Sciences, Christian
Medical College, Vellore, India, 6Casa di cura Sant’ Anna, Cagliari, Italy,
7Department of General Pediatrics, University Children’s Hospital, Muenster,
Germany.
Crisponi syndrome (CS) is a severe autosomal recessive disorder
manifesting in infancy, characterized by contractions of facial muscles,
dysmorphic features, camptodactyly, feeding and respiratory difficulties
. Characteristic hyperthermic crisis frequently lead to death within
the first months of life. Surviving patients usually develop a severe
progressive kyphoscoliosis requiring corset therapy or corrective surgery
. We have also observed paradoxical sweating after exposure to
low ambient temperature in some affected adolescents . We found that
mutations in the CRLF1 gene are associated with CS, showing allelism
with Cold Induced Sweating syndrome type 1 (CISS1) . We are
currently expanding the mutational analysis of CRLF1 gene on more
cases, which have been referred to our group . Up to now we found
four different novel mutations; two missense mutations in an Italian
patient, c .[338A>T;341T>C], p .[N113I;L114P]; one nonsense mutation
in a Turkish patient, c .829C>T, p .R277X; the deletion of the entire exon
1 in an Indian patient . All these mutations are present on both alleles in
the patients . CS and CISS1 belong to a group of conditions with overlapping
phenotypes, also including Cold-Induced Sweating syndrome
type 2 (CISS2) and Stüve-Wiedemann syndrome (SWS)/Schwartz-
Jampel syndrome type 2 (SJS2), all caused by mutations of genes
in the ciliary neurotrophic factor receptor (CNTFR) pathway . We are
currently characterizing in details the clinical phenotype of all the patients
collected with CS and CISS1 to establish a genotype/phenotype
correlation . These studies may yield valuable information for prospective
investigations of sweating disorders, thermoregulatory alterations
and bone development .
P01.272
Neonatal outcome of 937 children born after transfer of
cryopreserved embryos obtained by icsi and iVF and
comparison with data of fresh cycles
F. Belva1 , E. Van den Abbeel2 , M. Camus2 , P. Devroey2 , J. Van der Elst2 , I.
Liebaers1 , M. Bonduelle1 ;
1 2 Medical Genetics, UZ Brussel, Brussel, Belgium, Centre for Reproductive
Medicine, UZ Brussel, Brussel, Belgium.
Background To evaluate the safety of cryopreservation in combination
with IVF or ICSI, prenatal diagnosis and neonatal outcome were investigated
in children conceived from frozen-thawed ICSI embryos (cryo
ICSI) and frozen-thawed IVF embryos (cryo IVF) . Data were also compared
with earlier published results from fresh ICSI and IVF embryos .
Methods Questionnaire data and results of physical examination at
2 months of age of 547 cryo ICSI children and 390 cryo IVF children
were also compared with those of infants born after transfer of fresh
embryos .
Results Birth characteristics were comparable for cryo ICSI and cryo
IVF . Cryo singletons showed a trend towards higher mean birthweight
compared to fresh singletons, in ICSI and IVF, reaching significance
when all cryo (ICSI plus IVF) singletons were considered . Low birthweight
rate according to multiplicity was comparable between fresh
and cryo, in ICSI and IVF . Comparable rates of de-novo chromosomal
anomalies (3 .2%) were found in cryo ICSI fetuses/children versus the
fresh ICSI group (1 .7%) (Relative Risk 1 .93; 95% CI 0 .93-3 .99) . Major
malformations were more frequently observed at birth in cryo ICSI liveborns
(6 .4%) than in cryo IVF liveborns (3 .1%) (RR 2 .08; 95% CI 1 .09-
3 .95) and fresh ICSI liveborns (3 .4%) (RR 1 .89; 95% CI 1 .30-2 .76) .
Conclusion In cryo ICSI versus cryo IVF, prenatal and neonatal outcome
results were comparable besides a higher major malformation
rate in cryo ICSI . In the total cryo group versus the total fresh group,
we found a higher mean birthweight in singletons and a higher major
malformation rate in liveborns .
P01.273
Autosomal Recessive cutis Laxa syndrome revisited
E. Morava 1 , U. Kornak 2 , D. Lefeber 1 , Z. Urban 3 , S. Mundlos 2 , R. Wevers 1 ;
1 UMC Nijmegen, Nijmegen, The Netherlands, 2 Institute for Medical Genetics,
Charité Universitaetsmedizin Berlin, Berlin, Germany, 3 Wahington University,
StLouis, MO, United States.
The clinical spectrum of the autosomal recessive cutis laxa syndromes
is highly heterogeneous, both with respect to organ involvement and
severity . One of the major diagnostic criteria for cutis laxa is to detect
abnormal elastin fibers in skin biopsy. In several other, clinically similar
autosomal recessive syndromes, however, the classic histological
anomalies are not present, and the clinical diagnosis remains uncertain
. In some children with cutis laxa mutations have been demonstrated
in the elastin and fibulin genes, but the underlying genetic etiology
is still unknown in the majority of patients . Recently, mutations were
discovered in the ATP6V020 gene in several consanguineous families
with autosomal recessive cutis laxa . This genetic defect is associated
with abnormal glycosylation in the Golgi apparatus, leading to a distinct
combined N- and O-linked glycosylation disorder . Interestingly, similar
mutations were also confirmed in patients with wrinkly skin syndrome,
without the presence of severe skin symptoms with elastin deficiency.
These findings suggest that the cutis laxa and wrinkly skin syndromes
are phenotypic variants of the same disorder . The variable presence
of protein glycosylation disorders in patients with diverse phenotype in
the wrinkled skin-cutis laxa spectrum necessitates revisiting the definition
of clinical diagnostic criteria in order to offer adequate prognosis
assessment and counselling . Hereby we describe the spectrum of
clinical features of the various forms of ARCL syndrome . Based on the
recently unravelled novel disease entity we review the genetic aspects
including genotype-phenotype relations and suggest a practical diagnostic
approach .
P01.274
Unusual malformative association in Dandy-Walker syndrome
C. Jurca, M. Bembea, C. Skrypnyk, K. Kozma, A. Jurca, S. Bembea, S.
Costea;
Clinical Municipal Hospital “dr. G. Curteanu”, Oradea, Romania.
INTRODUCTION . Dandy-Walker syndrome (DWS) or Dandy-Walker
complex (DWC) is a rare congenital anomaly (1:25000 live births)