2008 Barcelona - European Society of Human Genetics

Clinical genetics
karyotyping . QMF-PCR permitted to detect one large deletion and six
small deletions generating premature stop codons .
The patients with small deletions had characteristic dysmorphic features
. All patients had severe developmental delay, late (after 5 years)
or absent walking, no speech, and microcephaly . We found a high incidence
of myopia in all patients who had undergone eye testing . We
frequently observed a happy disposition, stereotypic movements and
strabismus . In contrast, hyperventilation, epilepsy, constipation were
inconstant, and none of them had Hirschsprung disease or visceral
malformation .
Conclusion: We report 10 novel TCF4 deletions, in patients whose
phenotype strongly overlapped with PHS . However, we observed phenotypic
variations between the small deletions and the large genomic
deletions, which may lay the basis for further genotype-phenotype correlations
at the TCF4 locus . Owing to the large number of deletions
and microdeletions/insertions in TCF4 we would address to start the
molecular study by a QMF-PCR analysis .
P01.347
medical and auxological outcome in seventy 2-year-old
singletons born after embryo biopsy applied in preimplantation
genetic diagnosis or preimplantation genetic screening
S. Desmyttere 1 , J. De Schepper 2 , J. Nekkebroeck 3 , A. De Vos 4 , M. De Rijcke 1 ,
C. Staessen 1 , I. Liebaers 1 , M. Bonduelle 1 ;
1 UZBrussel, Centre for Medical Genetics, Brussels, Belgium, 2 UZBrussel,
Department of Pediatric Endocrinology, Brussels, Belgium, 3 VUB, Department
of Developmental- and Lifespan Psychology, Brussels, Belgium, 4 UZBrussel,
Centre for Reproductive Medicine, Brussels, Belgium.
Introduction: Limited data are available on the growth and clinical outcome
of children born after embryo biopsy . Embryo biopsy is an invasive
procedure to perform preimplantation genetic diagnosis (PGD)
or screening (PGS) . The objective was to determine if embryo biopsy
might cause prenatal and/or postnatal growth restriction and induce
congenital malformations .
Materials and methods: In this study we compared growth and physical
findings between seventy 2- year -old singletons born after PGD/
PGS compared to intracytoplasmatic sperm injection (ICSI) and spontaneous
conception (SC) . Children were matched for gender, maternal
educational level, mother tongue and birth order .
Results: No differences were found regarding weight, height and headcircumference
standard deviation scores at birth and at age two years .
Body Mass Index standard deviation score in PGD/PGS children at age
two years was lower compared to SC children (p = 0 .05) . PGD/PGS
children were more frequently born after caesarian section but had no
more congenital malformations, hospital admissions and surgical interventions
. Growth parameters within the PGD/PGS group of children
born after biopsy of one or two blastomeres were comparable .
Conclusions: Singleton children born after embryo biopsy applied in
PGD/PGS present a similar prenatal and early postnatal linear growth
compared to ICSI children and SC children . PGD/PGS singletons appear
not at higher risk for congenital malformations and surgical interventions
. Body Mass Index standard deviation score was slightly
lower in PGD/PGS children compared to SC children . There are no
observable detrimental effects of the PGD/PGS procedure on children
during the first years of life.
P01.348
Primary hyperoxaluria in italy
A. Robbiano 1 , G. Mandrile 1 , M. Petrarulo 2 , D. Pirulli 3 , C. Zadro 3 , D. Giachino 1 ,
M. Marangella 2 , A. Amoroso 4 , M. De Marchi 1 ;
1 Medical Genetics, University of Torino, Torino, Italy, 2 Renal Stone Centre,
Mauriziano Hosp., Torino, Italy, 3 University of Trieste, Trieste, Italy, 4 Dept. of
Genetics, Biology and Biochemistry, University of Torino, Torino, Italy.
Primary Hyperoxaluria (PH) is a rare autosomal recessive disease
with impaired hepatic detoxification of glyoxylate, due to AGT (PHI)
or GRHPR (PHII) enzyme deficiency. Oxalate overproduction in turn
causes nephrolithiasis, end-stage renal failure, systemic oxalosis and
multi-tissue damage . In responsive subjects an early biochemical and
genetic diagnosis can address to treatment with vitamin B6 (the AGT
cofactor) . In many cases liver or combined liver/kidney transplant is
necessary to correct the metabolic defect .
In a cohort of 47 PHI and 2 PHII Italian patients we identified the pathogenic
mutation of 90/94 PHI and 4/4 PHII alleles (96% mutation detec-
tion) using DHPLC and DNA sequencing .
Age at presentation varied from 1 month to 49 years (median 6 y) .
AGT residual activity in liver biopsies is available for 34 subjects . In
33 it was possible to define B6 responsiveness by comparing plasma
oxalate before and after oral supplementation .
23 different mutations were found (6 unpublished); missense mutations
affect evolutionary conserved residues and are absent in 160
chromosomes of healthy ethnically matched controls .
Genotype-phenotype correlations show an important role of non-genetic
factors as diet or delayed diagnosis, and confirm in our population
that the most frequent mutation G170R, causing mitochondrial
mistargeting, is associated with a mild phenotype (residual enzymatic
activity, late onset and responsiveness to B6) . For missense (G116R)
and insdel inframe (c .283dupGAG) mutations we presume an antimorphic
effect as they were found only in patients with a severe phenotype
despite the presence of a mild mutation on the other allele .
P01.349
Wiedemann-Rautenstrauch syndrome:case report
A. Laku (Babameto) 1 , V. Mokin 1 , L. Grimci 2 ;
1 University Hospital Center”Mother Theresa”, Service of Medical Genetics, Tirana,
Albania, 2 University Hospital Center”Mother Theresa”, Service of Pediatric
Endocrinology, Tirana, Albania.
Wiedemann-Rautenstrauch syndrome or neonatal progeroid syndrome
is a rare autosomal recessive disorder, with few published case
reports . WRS is characterized by progeroid appearance at birth, lipoatrophy,
slow growth .
We report a 8 months old female, the fourth child of a healthy nonconsanguineous
couple . The pregnancy was unremarkable . The birth was
at term with prenatal hypoplasia and aged signs present at birth . (BW
2500 g, BL 47 cm) . At age of 8 months old progeroid appearance became
more pronounced . The patient showed growth delay (W=3,9kg;
L=60cm,), muscle hypotrophy, psychomotor retardation and typical
progeroid features; senile-appearing triangular face, beak-shaped
nose, microstomia, micrognathia, congenital incisors, hidrocephaloid
cranium, widened fontanelles and sutures, prominent veins on scalp,
hypotrichosis, relatively large fingers and toes, wrinkled skin, lipoatrophy
with scleroderma-like changes of skin on the buttocks . She had
feeding problems .
Congenital cataract and glaucoma were revealed . Ultrasound examination
of brain, heart and abdomen did not reveal any abnormalities .
Chromosomal and biochemical analyses were normal . Clinical features
of our patient were compared with published data of WR syndrome,
other premature aging syndromes, nonclassified progeroid conditions.
We have established “neonatal progeroid Wiedemann-Rautenstrauch
syndrome” based on association of characteristic aging appearance
present at birth, failure to thrive, deficient growth and development, hypotrichosis,
signs of generalized lypoatrophy, scleroderma-like changes
of skin on the buttocks and congenital incisors . The parents were
informed about the genetic risk of recurrence .
P01.350
A case report of proteus syndrome
I. Chelly, F. Maazoul, L. Kraoua, I. Ouertani, M. Chaabouni, L. Ben Jemaa, R.
Mrad, H. Chaabouni;
department of heridatary and congenital disorders, Tunis, Tunisia.
Proteus Syndrome (PS) was initially described in 1979 by Cohen and
Hayden and assigned its name several years later in 1983 by Wiedemann
. This is a relatively recently delineated syndrome, probably
because it is so rare and because it overlaps with a number of other
asymmetric overgrowth syndromes .
The disorder primarily manifests as postnatal overgrowth, with irregular,
distorting and progressive overgrowth that can include many tissues
essentially connective tissue, bone, skin, central nervous system,
and the eye .
The overgrowth of PS is progressive and can be difficult to manage. It
can cause severe orthopaedic complications .
One of the most common complications in patients with PS is deep
venous thrombosis and pulmonary embolism, which can cause premature
death .
The management of this syndrome requires knowledge of the wide array
of manifestations and complications and a multidisciplinary approach .
Patients with PS have an increased risk of developing tumours .