2008 Barcelona - European Society of Human Genetics

Cytogenetics
3 Paediatrics, Hospital Universitari Son Dureta, Palma de Mallorca, Spain, 4 Genetics,
Hospital Universitario La Paz, Universidad Autónoma de Madrid, Madrid,
Spain, 5 Gynecology, Hospital Universitari Son Dureta, Palma de Mallorca,
Spain, 6 Obstetrics and Gynecology, Hospital Fundació Son Llatzer, Palma de
Mallorca, Spain.
The phenotype of patients with del22q11 .2 is very variable and ranges
from the more severe and complex forms of the DiGeorge and Velocardiofacial
syndromes, to isolated heart defects or isolated mental
disorders . TBX1 and CRKL are genes localized in 22q11 .2 which have
been proposed to cause the associated phenotype . We present here
the results of the characterization of deletions, duplications and mutations
in the TBX1 and CRKL genes in prenatal samples, newborn and
children with compatible malformations or phenotype . Duplications
and deletions were studied by the use of a combination of a homebrew
method based on microsatellites, MLPA (SALSA 23 and 250),
CGH-arrays and FISH . Mutations in TBX1 and CRKL were analysed
by sequencing. In total, we have identified 21 patients with a 22q11.2
deletion (1 .5 and 3 Mb) and one patient with a previously not described
1 Mb duplication . In patients with no deletions or duplications we found
two mutations in TBX1 . The atypical duplication was found in a boy
with a ventricular septal defect (VSD) as the sole phenotypic trait . Neither
his normal parents nor his sister which is also affected by a VSD
are carriers of such duplication . The size of the duplication is approximately
1 Mb and is flanked by LCR22s 3a (B) and 4 (D) a region that
includes the CRKL gene but not TBX1.
This work has been supported by the grant FIS 05-1585 from the Instituto
de Salud Carlos III from the Spanish ministry of Health.
P02.074
clinical and molecular characterization of 7 patients with
22q13.3 deletion syndrome
M. Palomares Bralo 1,2 , L. Fernández 1,2 , P. Lapunzina 1,2 , E. Galán 3 , L. Pérez
Jurado 4,5 , B. Rodríguez Santiago 6,5 , C. Roche 7 , P. O. Ruiz Falló 8 , A. Delicado 1,9 ;
1 Genética Médica, Hospital Universitario La Paz, Madrid, Spain, 2 Centro de
Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid,
Spain, 3 Unidad de Genética. Hospital Materno Infantil Universitario Infanta Cristina,
Badajoz, Spain, 4 Unidad de Genética. Departamento de Ciencias Experimentales
y de la Salud. Universidad Pompeu Fabra., Barcelona, Spain, 5 Centro
de Investigación Biomédica en Red de Enfermedades Raras (CIBERER),
Barcelona, Spain, 6 Unidad de Genética. Departamento de Ciencias Experimentales
y de la Salud. Universidad Pompeu Fabra, Barcelona, Spain, 7 Neurología
Pediátrica, Hospital Universitario La Paz, Madrid, Spain, 8 Neurología, Hospital
Niño Jesús, Madrid, Spain, 9 Centro de Investigación Biomédica en Red de
Enfermedades Raras (CIBERER), Barcelona, Spain, Madrid, Spain.
In recent years the increasing use of telomere screening has provided
evidences of the presence of subtle abnormalities involving telomeres
in around 5% of patients with idiopathic mental retardation . This fact
has allowed the recognition of new distinct clinical entities such as
monsomy 1p, 1q, 2q, 9q, 14q, and 22q . In surveys of subtelomeric
screening, deletion of 22q13 .3 is the second most common subtelomeric
deletion, after deletion 1p36 .3 . The prevalence of 22q13 .3 deletion
is not yet established . Up to the present moment more than 100
cases have been reported, and a common phenotype has emerged
including global developmental delay, hypotonia, absent to severely
delayed speech, autistic-like behavior, normal to accelerated growth,
and dysmorphic facial features . In spite of the increasing number of
cases reported, this syndrome remains underdiagnosed due to the difficulty
to detect the deletion of chromosome 22 in routine cytogenetic
analysis even at the 550-band level of resolution, and to the lack of a
distinct phenotype and the clinical variability observed .
Here we describe the clinical and molecular findings in 7 patients
with monosomy 22q13 . Three of them were detected by subtelomeric
screening, other two were fortuitously discovered when FISH was
used to rule out DGS/VCFS, and two were observed in the karyotype
and subsequently confirmed by FISH.
All of them where further studied in detail by MLPA, using the specific
probe mix P188 for 22q13 deletion syndrome, and arrayCGH at approximately
1 Mb resolution .
P02.075
Phenotype of a patient with pure partial trisomy 2p(p21-->pter)
M. Akbary 1,2 , F. Mahjoubi 3,1 , N. Zolfagary 1 ;
1 Tehran Medical Genetic Laboratory, Taleganee St, Tehran, Iran, Tehran, Islamic
Republic of Iran, 2 Medical Genetic Dept., Tarbiat Modaress University,
Tehran, Iran, Tehran, Islamic Republic of Iran, 3 NIGEB, Tehran, Islamic Republic
of Iran.
We present the case of a 7-year -old boy with additional material on
4q. The father’s karyotype confirmed that the additional segment on 4q
was of chromosome 2p origin, resulting in trisomy 2p21 -->2pter . The
karyotype of the proband was found as 46, XY,der(4)t(2;4)(p21;q33)
pat .
His father’s karyotype was 46, XY, t(2;4)(p21;q33) . The mother had
normal karyotype . The child was found to have dysmorphic facial features,
prominent ears, long fingers, short stature, thenar and hypothenar
atrophy, crowded teeth, high arched palate, prognathism, low
nasal bridge, large testes, developmental delay, speech delay and seizures
. This case will be compared with other reported cases of partial
trisomy/duplication of 2p .
P02.076
47,XYY/48,XXYY karyotype associated with multiple skeletal
abnormalities and congenital heart disease
L. Mutesa1 , G. Pierquin1 , J. Vanbellinghen1 , A. Hellin1 , M. Jamar1 , C. De Beaufort2
, J. Kieffer2 , V. Bours1 ;
1 2 University of Liège, Liège, Belgium, Luxembourg Hospital Center, Luxembourg,
Luxembourg.
We report on a 12-year-old boy with congenital scoliosis due to segmented
hemivertebra between tenth and twelfth thoracic vertebrae . He
had also congenital heart disease (atrial septal defect) and presented
bilateral synostosis of the proximal radius and ulna associated with
dislocation of both radius heads . Physical examination revealed facial
dysmorphism, mild microcephaly, gynecomastia with morbid obesity,
limitation of supination at the elbows, and moderate mental retardation
.
Cytogenetic studies and FISH analysis showed that he had a de novo
47,XYY/48,XXYY karyotype . This case and evidence collected from
the literature suggest that congenital skeletal abnormalities and heart
defect may occur in the 47,XYY/48,XXYY syndrome more frequently
than currently appreciated . The 47,XYY/48,XXYY phenotype may
result from compounding affects of the additional X and Y chromosomes
.
P02.077
severe neurological phenotype in a boy with 48, XXYY karyotype
M. Bordignon, K. Ludwig, L. Salviati, R. Tenconi;
Servizio di Genetica Clinica, Padova, Italy.
A 18 month old boy was seen in our clinical genetics unit for further
evaluation after having been diagnosed with 48, XXYY aneuploidy . He
had a history of epileptic seizures, mental retardation, left cryptorchidism
and a first degree atrio-ventricular block.
A thorough examination of the boy revealed many of the clinical features
characteristically found in patients with gonosomal polysomies,
as for example the truncular obesity, slight hypogenitalism, mental retardation
and facial dysmorphisms (coarse face, mild frontal bossing,
brachycephaly, bilateral epicanthic folds and maxillary hypoplasia .) .
However he also presented generalized hypotonia, epileptic seizures
and paroxysmal sharp-waves and polyspikes in the central occipital
left hemispheral region on EEG analysis; neurological findings which
have rarely described in patients with 48, XXYY karyotype .
The incidence of the 48,XXYY aneuploidy is about 1 in 50,000 newborns
and initially it had been classified as a variant of Klinefelter
Syndrome. Today it is defined as an independent genetic and clinical
entity .
As far as we know, this is the first case report of a boy with the 48,
XXYY chromosomal anomaly presenting epileptic seizures as one of
the major clinical features .