2009 Vienna - European Society of Human Genetics

Cytogenetics
bridization) techniques.
In 25 peripheral blood samples were applied conventional cytogenetic
techniques and FISH with the use of probes specific for the subtelomeric
chromosomes regions.
The authors present the results, comparing them with those described
in the literature.
Supported by the Commission for Promotion of Research in Health
Care: Research Project in Applied Health Care - Nº 5/2007
P03.170
clinical features in 102 patients with Angelman syndrome
W. Tan 1 , C. A. Bacino 2 , S. A. Skinner 3 , S. A. Skinner 3 , I. Anselm 1 , R. Barbieri-Welge
4 , A. Baeur-Carlin 3 , A. L. Beaudet 2 , T. Bichell 5 , J. K. Gentile 1 , D. G.
Glaze 2 , L. T. Horowitz 3 , H. Lee 6 , M. P. Nespeca 4 , S. U. Peters 2 , T. Sahoo 2,7 , D.
Sarco 1 , S. E. Waisbren 1 , L. M. Bird 4 ;
1 Children’s Hospital Boston, Boston, MA, United States, 2 Baylor College of
Medicine, Houston, TX, United States, 3 Greenwood Genetic Center, Greenwood,
SC, United States, 4 Rady Children’s Hospital San Diego, San Diego, CA,
United States, 5 Vanderbilt University, Kennedy Center, Nashville, TN, United
States, 6 Data Technology Coordinating Center, University of South Florida,
Tampa, FL, United States, 7 Signature Genomic Laboratories, Spokane, WA,
United States.
Background: Angelman syndrome (AS) is a neurodevelopmental disorder
caused by a lack of expression of the maternal copy of UBE3A.
We are conducting a 5-year longitudinal study on the natural history
of AS, to improve our understanding of the complications, morbidity
and neurodevelopment in AS. We present the baseline clinical data
that describes characteristics of the first 102 subjects enrolled in our
study.
Methods: All subjects were between 5 months and 26 years old. Subjects
were evaluated by detailed history, physical examination, standardized
neurodevelopmental assessments, and electroencephalograms
(EEG). Deletions were sized using a chromosome 15-specific
comparative genomic hybridization microarray.
Results: The median age of the 102 subjects was 36 months (80%
were between 17 months and 60 months). 74% of subjects had deletions,
15% had either imprinting defects or uniparental disomy, and
12% had UBE3A mutations. The most common findings were mouthing
behavior in 93%, short attention span in 91%, microcephaly in 81%,
sleep difficulties in 79%, ataxic or broad-based gait in 78%, fascination
with water in 75%, and inappropriate laughter was observed in 62% of
subjects. Clinical seizures were reported in 69% of subjects, although
all EEGs were abnormal. Data on the variations in these characteristics
by molecular subtype will be presented.
Conclusions: In children with AS, it is the neurobehavioral phenotype,
rather than the dysmorphic features or seizures, that is most characteristic.
The “classic” AS phenotype is more frequently observed in
those with deletions or UBE3A mutations, and not as evident in those
with UPD or imprinting defects.
P03.171
Particular forms of Prader Willi syndrome - clinical and genetic
study
C. Rusu1 , C. Vulpoi1 , E. Braha1 , M. Volosciuc2 , V. Gorduza1 , C. Gorduza3 , M.
Covic1 ;
1 2 3 University of Medicine, Iasi, Romania, Children’s Hospital, Iasi, Romania, ”Sf
Spiridon” Hospital, Iasi, Romania.
Prader-Willi syndrome (PWS) is a relatively common disorder due to
abnormalities in the 15q11.2-q13 region. Major manifestations include
hypotonia with poor suck and poor weight gain in infancy, early childhood-onset
hyperphagia and obesity, characteristic appearance, hypogonadism,
growth hormone insufficiency causing short stature, mild
mental retardation and characteristic behaviour.
We present 3 particular cases of PWS recorded in the files of Iasi Medical
Genetics Center in order to illustrate some special features and
to discuss the diagnosis and management strategy. In all 3 cases the
suspicion of diagnosis was based on actualized diagnostic criteria.
Case 1: 10 years old girl with typical neonatal hypotonia and poor
weight gain in infancy followed by marked hyperphagia and obesity,
acromicria and hypogonadism, but with tall stature, multiple severe
allergies, severe mental retardation and seizures. Genetic defect: microdeletion
identified by FISH;
Case 2: 6 years old girl with neonatal hypotonia and feeding difficulties
followed by marked obesity, but with macrocephaly, inexpressive face
and severe tibia vara. Genetic defect: imprinting defect;
Case 3: 20 years old boy with typical neonatal hypotonia and poor
weight gain in infancy followed by mild obesity and relatively normal
apetite, acromicria (but with shortening of the 4 th metacarpal) and a
particular psychological profile. Genetic defect: 15q deletion identified
on the karyotype.
Clinical features, diagnosis and management will be illustrated in detail.In
conclusion, we present 3 particular cases of PWS in order to
illustrate some special features and to discuss the diagnosis and management
strategy.
P03.172
Oro-dental phenotypic spectrum of patients with PWs
C. Bortun1 , L. Ardelean1 , M. Puiu2 ;
1 2 Faculty of Dental Medicine, Timisoara, Romania, University of Medicine and
Pharmacy V. Babes, Timisoara, Romania.
Background. Prader-Willi Syndrome (PWS) is a rare genetic disorder
caused by genetic defects in certain regions of chromosome 15q11-
13. Commonly associated characteristics of this disorder include hypotonia,
obesity, mental retardation, short stature, hypogonadotropic hypogonadism,
small hands and feet, facial dysmorphy, learning and behavioural
difficulties, and dental abnormalities (thick viscous saliva).
Aim. To describe the oro-dental phenotypic spectrum of patients with
PWS.
Design. Five PWS patients (5-22 years of age) being followed at the
Emergency Children Hospital L. Turcanu, Timisoara were examined at
the dental clinic of the same institution. Medical information collected
included all clinical manifestation, body mass index (BMI), level of cognitive
functioning, genetic investigations. Oral and radiological evaluations
were performed.
Results. All 5 patients had caries experience, dental erosion and salivary
flow rates were assessed.
Conclussion. The clinical implications of the dental anomalies, with
genetically controlled patterns are important in establishment of early
diagnosis and appropriate orthodontic care and collaboration between
dentist, geneticist and pediatrician ensure a formula of a correct diagnosis
and in giving an adequate therapeutical advice.
P03.173
contributions to expanding the concept genetic-epigenetic and
the correlation phenotype-genotype in Prader-Willi/Angelman
syndromes
M. Stoian1 , V. Belengeanu1 , N. Cucu2 , M. Puiu1 ;
1University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania,
2Faculty of Biology, University of Bucharest, Bucharest, Romania.
Prader-Willi and Angelman syndromes are two distinct neurodevelopmental
disorders, caused by several genetic/epigenetic mechanisms
involving chromosome 15. Recent studies revealed differences in
different classes of PWS/AS against previous ones. This aspect supports
the requirement of extending the investigation protocols for the
patients in order to acquire an early diagnosis, an accurate etiological
subtype that will support an adequate genetic counseling and an
efficient management of the disease. We initiated a project and we
propose to identify possible factors involved in etiology of altering of
the imprinting process, by applying adapted surveys for the families of
the patients, including many generations. Applications of genetic and
epigenetic testing relevant for subtypes of PWS/AS and the introduction
of chromatin remodeling tests by chromatin inmmunoprecipitation
assay and possibility of TOF mass spectrometry are original and complex
aspects that this study has as objectives. In the first three months
from the start off of this project we investigated the first four patients (1
boy and 3 girls) that were included in the study. The phenotype of the
patients allowed as according to clinical criteria to set the PWS diagnose.
For all patients FISH analysis was performed using Vysis Prader-Willi/Angelman
Region Probe - LSI SNRPN SpectrumOrange/CEP
15 (D15Z1) SpectrumGreen/LSI PML SpectrumOrange probe. For one
of the patients the deletion was positive and for the rest the result was
negative. The complex epigenetic analysis is to be performed remaining
that the results to be included in the presentation.