2009 Vienna - European Society of Human Genetics

Cytogenetics
grandmother and 2 maternal aunts with bipolar disorders. Biochemical
and metabolic testing for inborn errors of metabolism and Fragile X
DNA analysis were all normal. Chromosome microarray analysis revealed
an XX female with 0.334 Mb duplication and a 0.984 Mb deletion
at 1q21.1.Her brother with hearing problems who presented 2
months later with aggressive behaviour was shown to carry the same
0.334 Mb duplication and a 1.06 Mb deletion at 1q21.1.(Parental studies
are not available yet).
Identification of 1q21.1 rearrangements should prompt the clinicians to
evaluate the other members of the family and closely follow up the patients
carrying these rearrangements. Given the spectrum of possible
outcomes, there may be cases with subtle, undiagnosed findings (in
our case, psychiatric problems in a brother) and early diagnosis might
improve outcome.
P03.066
cortical dysplasia and craniofacial dysmorphism in a child with
interstitial microdeletion of 7q22.1-7q22.3 detected by array
comparative genomic hybridization
Z. N. Al-Hassnan1,2 , N. Kaya1 ;
1King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia,
2Alfaisal University, Riyadh, Saudi Arabia.
Array comparative genomic hybridization (aCGH) has proved useful
as a diagnostic tool for patients with developmental delay, craniofacial
dysmorphism, and normal karyotyping. Here we report the findings in
a 4 year old boy who was referred to our center for evaluation of developmental
delay and dysmorphic features. He was born at term with
uneventful prenatal and neonatal periods. His parents, who have 4
other normal children, noticed that he had developmental delay since
early infancy. His examination showed that he had macrocephaly, malformed
right ear, retrognathia, hypotnia, and undescended testes. Brain
MR imaging showed hypoplasia of the corpus callosum and thickening
in the cortex of the frontal lobes predominantly in the singulate gyrus
suggestive of cortical dysplasia. MR Spectroscopy was unremarkable.
Karyotyping with 725 band resolution was normal. FISH for subtelomeric
cryptic rearrangements / deletions / duplications was negative.
Array CGH using a custom oligonucleotide microarray revealed an interstitial
microdeletion of 7q22.1 to 7q22.3, spanning approximately
3.5 megabases. The deletion was confirmed by FISH study. To our
knowledge, this particular microdeletion has not been reported in literature
using aCGH. The phenotype we describe here in our patient
may represent a unique genomic syndrome of 7q22.1-q22.3 microdeletion
that could be clinically recognizable. Furthermore, our report
supports the value of incorporating aCGH in the evaluation of patients
with undiagnosed developmental delay and dysmorphism.
P03.067
Recurrence of a de novo 2q22.1q22.3 deletion identified by
array-cGH in two sibling foetuses presenting precocious
lymphoedema and associated malformations
A. Dieux-Coëslier 1 , B. Delobel 2 , P. Deruelle 3 , V. Houfflin-Debarge 3 , S. Manouvrier
1 , J. Andrieux 4 ;
1 Service de Génétique Clinique, Hôpital Jeanne de Flandre, Lille, France,
2 Service de Génétique Chromosomique, Hôpital Saint-Vincent, Lille, France,
3 Service de Gynécologie Obstétrique, Hôpital Jeanne de Flandre, Lille, France,
4 Laboratoire de Génétique Médicale, Hôpital Jeanne de Flandre, Lille, France.
We report on two sibling foetuses presenting major lymphoedema during
the first trimester of pregnancy, associated with several malformations.
They were born from healthy and unrelated young parents. The
first pregnancy was interrupted at 13 weeks of gestation because of
the severity of the lymphoedema. Karyotype on chorionic villus sample
was normal. Pathology revealed in a male foetus the association of a
common mesentery, a unique ectopic testis and small renal cysts.
The second pregnancy was terminated at 15 weeks of gestation. The
female foetus presented a generalized lymphoedema, a single umbilical
artery and bilateral hydronephrosis.
Both foetus and parents had normal conventional chromosomal analysis.
Array-CGH revealed a 6.7 Mb 2q22.1q22.3 deletion encompassing
five genes in the two foetuses. Deleted genes in this region were
LRP1B, KYNU, ARHGAP15, GTDC1 and ZEB2. The latter is known to
be involved in Mowat-Wilson syndrome.
No parental anomaly was detected by array-CGH. In addition, FISH
analysis on both parents confirmed the de novo deletion. Recurrence
was explained by a presumed germline mosaïcism.
Reported cases with identical structural chromosomal aberrations
born to karyotypically normal parents are rare. Gonadal mosaïcism is
well documented for autosomal dominant and X-linked disorders, but
seems to be very rare for this type of chromosomal anomaly. Array-
CGH analysis can therefore be very helpful to identify small structural
chromosomal aberration in foetuses with unusual multiple congenital
anomalies syndromes, and for adequate genetic counselling.
P03.068
De novo 2q36.1-q36.2 including PAX deletion in a patient with
atypical Waardenburg syndrome type 1
S. Lejeune-Dumoulin 1 , J. Andrieux 2,3 , J. Ghoumid 1 , S. Joriot 4 , M. Holder-Espinasse
1,3 , S. Manouvrier-Hanu 1,3 ;
1 Clinical Genetic Department, CHRU Lille, Lille, France, 2 Genetic Department,
CHRU Lille, Lille, France, 3 Lille 2 University, Lille, France, 4 Paediatric Department,
CHRU Lille, Lille, France.
Waardenburg syndrome (WS) accounts for 2% of congenital deafness.
It is a heterogeneous group of diseases divided into 4 subtypes.
WS3 associates hearing impairment, abnormal pigmentation, dystopia
canthorum and limb anomalies. This condition is due to mutations or
deletions of PAX3 gene. Mutations in PAX3 have also been reported in
the craniofacial-deafness-hand syndrome (CDHS), a rare form of WS,
which comprises a flat midface, hypertelorism, a hypoplastic nose and
limb anomalies.
Here we report on a four year-old boy referred to the genetic clinic for
bilateral hand arthrogryposis. He also presented dysmorphic features
such as a flat and asymmetrical face, severe dystopia canthorum and
a small mouth. Neither depigmentation nor gastro-intestinal involvements
were noted.
He was born at 38 WG with the following growth parameters: 1.650
kg (