2008 Barcelona - European Society of Human Genetics

Cytogenetics
deleted region contains a gene responsible for the cognitive impairment
observed in our patient . 10p15 microdeletions has already been
described in few patients will almost identical symptoms and similar
dysmorphic features. This confirms the existence of a recognizable
albeit rare microdeletion syndrome with HDR and autism .
P02.069
the developing facial phenotype of the 17q21.31 microdeletion
syndrome.
N. Van der Aa 1 , L. Rooms 2 , B. Ceulemans 1 , B. de Vries 3 , F. Kooy 2 ;
1 Antwerp University Hospital, Edegem, Belgium, 2 University of Antwerp, Wilrijk,
Belgium, 3 Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands.
The 17q21 .31 microdeletion syndrome is a new genomic disorder,
characterized
by a 500-650 kb submicroscopic deletion .
Patients have a recognizable phenotype including neonatal hypotonia,
mental retardation and characteristic facial features, most notably a
long face, large prominent ears and a tubular pear-shaped nose .
We present a patient with a de novo 17q21 .31 microdeletion, identified
by multiplex ligation-dependent probe amplification with probes
hybridizing to unique sequences in 2 genes located within this region,
MAPT and CRHR1 .
This boy was born at term with normal growth parameters . There was
marked neonatal
hypotonia with feeding difficulties and necessity of nasogastric tube
feeding .
Early motor milestones were significantly delayed. IQ testing at the
age of 6 revealed mild mental retardation . Dysmorphic facial features
noted in infancy were epicanthic folds, upslanting palpebral fissures,
mild ptosis, low-set ears, a broad nose and prominent philtrum .
As the boy got older, the chin got bigger, there was marked elongation
of the face and the nose became more pronounced . Subsequent
pictures of our patient from age 6 months till 13,5 years illustrate this .
At diagnosis age 13,5 we note a very long narrow face, large ears
and a very prominent tubular pear-shaped nose with broad nasal tip .
The palate is very high and there is dental crowding . We note thoracic
scoliosis, wide-spaced nipples, a right pes cavus, numerous skin
moles and a rather severe ichthyosis on hands and feet . He has nasal
speech and a very friendly nature .
This is the first extensive description of the syndrome’s developing
phenotype .
P02.070
cognitive and behavioral patterns associated with 18p-
L. O’Donnell, B. T. Soileau, C. D. Sebold, J. D. Cody;
Chromosome 18 Clinical Research Center, San Antonio, TX, United States.
Background. While deletions of 18p- are associated with short stature
and minor dysmorphic features, no clear cut cognitive or behavioral
patterns have emerged . Included in our longitudinal study of persons
with chromosome 18 differences is a large cohort of persons with chromosome
18p- . Adaptive behavior assessment measures everyday activities
while cognitive measures assess internal cognitive processes .
Currently no information is available regarding the correspondence
between adaptive behavior and cognitive development for this population
. Methods. The adaptive behavior of 10 individuals with 18p-
were evaluated using the Vineland Adaptive Behavior Scales (Vineland;
Sparrow, Balla & Cicchetti, 1984) and estimates of intellectual
functioning were gathered using either the Differential Abilities Scales
(DAS, Elliott, 1990) or the Bayley Scales of Infant Development-Second
Edition (Bailey-II, Bailey, 1993) . All scores were converted to standard
scores with a mean of 100 and standard deviation of 15 . Results.
Intellectual functioning varied from significant cognitive impairment
(N=3) to low average/average intellectual functioning (N= 3) . Adaptive
behavior skill development was commensurate with estimates of intellectual
functioning in only three of the nine children’s profiles. In the
remaining six cases, estimates of cognitive development were lower
than parental ratings of adaptive behavior . Conclusions. This study
supports previous findings of significant cognitive variability within the
18p- population. It provides evidence of significant adaptive skill variability
and also highlights within subject variability in cognitive and behavioral
development. These findings suggest that for persons with
18p- deletions, it is critical to utilize both cognitive and behavioral mea-
sures to more fully understand development .
P02.071
Endocrine abnormalities in 18p-
D. E. Hale, C. D. Sebold, J. D. Cody;
Chromosome 18 Clinical Research Center, San Antonio, TX, United States.
Background. 18p- syndrome has primarily been described in case reports
and small series . An endocrine abnormality is present in ~20% of
reported cases . The aim of this study was to determine the incidence
and types of endocrine abnormalities in our population . Methods.
Eleven individuals with 18p- underwent an endocrine evaluation at the
Chromosome 18 Clinical Research Center (the “Center”) . This evaluation
included anthropomorphics, bone age studies and growth (growth
factors and stimulation testing) and thyroid hormone testing . In addition,
a review of the available medical records for 20 additional patients
was completed . Results. Five males and 6 females were evaluated at
the Center . The average age was 9 8 / 12 years (range 2 8 / 12 to 18 2 / 12 ) .
Six individuals were