European Human Genetics Conference 2007 June 16 – 19, 2007 ...

Clinical genetics
P0105. APC gene mutations in Polish FAP patients
A. Plawski 1 , M. Podralska 1 , T. Banasiewicz 2 , P. Krokowicz 3 , D. Lipinski 1 , R.
Slomski 1 ;
1 Instytitute of Human Genetics, Poznan, Poland, 2 Department of General,
Gastroenterological and Endocrinological Surgery, University of the Medical
Sciences, Poznan, Poland, 3 Department of Surgery University of the Medical
Sciences, Poznan, Poland.
Familial adenomatous polyposis (FAP) is an autosomal dominant, predisposed
disorder that results in the development of numerous polyps
in the colon and rectum, usually beginning in childhood or adolescence.
Other extracolonic features may include polyps in the upper parts of
the gastroenterological tract, desmoid tumours, ocular lesions, osteomas,
dental abnormalities, and malignancies in other organs. FAP incidence
is estimated at 1:10,000. FAP arises due to germ line mutations
in the adenomatous polyposis coli (APC) gene, consisting of 8.529 bp
open reading frame and encoding a 2.843 amino acid protein.
Seven hundreds DNA samples from persons belonging to 280 Polish
FAP families were collected. 380 patients were diagnosed with FAP.
The entire APC gene was screened for mutations in 240 families. The
APC gene point mutations were identified in 115 FAP families. Thirty of
them have not been described before. Seven mutation types recurred
two or more times. The recurrent mutations were detected in 52% of
diagnosed families. The large rearrangements of the APC gene were
studied in 95 FAP families without the point mutation. In this group we
identified 14 large APC gene rearrangements with two cases of whole
APC gene deletions.
This work was funded by the Ministry of Education and Science, Poland,
grant number 2PO5A10728
P0106. A new familial case of Gollop-Wolfgang syndrome
confirming an Autosomal Recessive mode of inheritance
B. I. Dimitrov1 , A. Debeer2 , L. Johan3 , K. Devriendt1 ;
1Centre for Human Genetics, University Hospital Leuven, Leuven, Belgium,
2 3 Neonatology Unit, University Hospital Leuven, Leuven, Belgium, Department
of Orthopedics, University of Leuven, Leuven, Belgium.
Gollop-Wolfgang syndrome is a rare condition of unknown aetiology
characterized by the presence of femur bifurcation, tibial agenesis and
ectrodactyly. Several additional abnormalities such as congenital heart
defects, vertebral segmentation defects, ribs and CNS anomalies have
been described. Based on an affected child of a consanguineous Arab
family with additionally similarly diseased relatives, an autosomal recessive
type of inheritance was supposed. However the presence of
sporadic cases with unrelated parents as well as an association of a
single case with proximal deletion of chromosome 8p suggests the
existence of a dominant form.
We report on a newborn child of consanguineous Turkish family presenting
unilateral bifid femur and ipsilateral ectrodactyly of the hand
and foot. No additional abnormalities have been observed. Later on
we were able to examine her 13 year old uncle who has similar but bilateral
hand and limb anomalies. Mental development was normal, and
he presented no other anomalies. The present case strongly supports
an autosomal recessive type of inheritance of this condition. A possible
pathway and classification of the femur bifurcation-tibial a/hypoplasia
complex will be discussed.
P0107. Fetal Alcohol Spectrum Disorder - a clinical study and
suggestions for an adapted questionaire concerning fetal
exposure in Romania
R. Popescu 1 , C. Rusu 2 , M. Volosciuc 2 , E. Braha 2 , L. Butnariu 2 , M. Covic 2 ;
1 Children’s Hospital Iasi - Medical Genetics Center, Iasi, Romania, 2 University
of Medicine and Pharmacy- Department of Medical Genetics, Iasi, Romania.
Fetal Alcohol Spectrum Disorder (FASD) refers to disabilities caused
by prenatal exposure to alcohol - fetal alcohol syndrome(FAS), partial
fetal alcohol syndrome(p-FAS) and alcohol related neurodevelopmental
disorders(ARND). FAS is defined by: pre/postnatal growth retardation,
facial dismorphysm and SNC dysfunction.
We have used the Canadian guidelines for FASD to analyze our patients
in order to appreciate their importance in establishing the diagnosis.
This involved evaluation score for upper lip, philtrum, palpebral
fissures, impaired pre/postnatal growth, CNS/neurobehavioural disorders
and gestational exposure to alcohol.
63 children (FASD in observation between 1994-2006) were selected
for the study. Only 47 patients fulfilled the criteria for FASD (25 -definite
FAS, 6 -p-FAS and 5 -ARND). The 11 children left remain in observation
due to young age.
We have analyzed the frequency of defining characteristics for every
category: for FAS children - microcephaly (100%), postnatal growth retardation
(76%), smooth/flattened philtrum rank 5 (56%), thin upper lip
rank 5 (60%), moderate mental retardation (80%), learning difficulties
and attention deficit/hyperactivity disorder (100%). Prenatal alcohol exposure
was confirmed in 44% of cases. Other defects recorded: heart
defects, genitourinary, ocular abnormalities and hernia.
Patients diagnosed with p-FAS and ARND present similar characteristics.
The screening questionaire for maternal alcohol history didn’t fit to
our population and we have adapted it. The detailed protocol as well
as the differential diagnosis will be presented.
In conclusion, we appreciate that the guidelines are very useful for
FASD diagnosis and we have adapted the protocol for our population
in order to optimize FASD diagnosis.
P0108. Clinical features in patients with Opitz-Kaveggia (FG)
syndrome and a recurrent mutation, p.R961W, in the MED12
gene
J. M. Graham 1 , H. Risheg 2 , R. C. Rogers 2 , R. D. Clark 3 , K. Jones 4 , J. B. Moeschler
5 , M. May 2 , S. M. Joseph 2 , J. R. Jones 2 , C. E. Schwartz 2 , M. J. Friez 2 , R.
E. Stevenson 2 ;
1 Cedars Sinai Medical Center, Los Angeles, CA, United States, 2 Greenwood
Genetic Center, Greenwood, SC, United States, 3 Loma Linda University Children’s
Hospital, Loma Linda, CA, United States, 4 USCD School of Medicine,
San Diego, CA, United States, 5 Dartmouth-Hitchcock Medical Center, Lebanon,
NH, United States.
Opitz and Kaveggia (1974) reported a family of 5 affected males with
mental retardation, macrocephaly, imperforate anus and hypotonia,
and Risheg et al. (2007) reported an identical nucleotide substitution
(c.2881C>T) in exon 21 of MED12 causing tryptophan to replace arginine
at amino acid 961 (p.R961W) in 6 families with Opitz-Kaveggia
syndrome (13% of 45 clinically-diagnosed cases), including the only
surviving affected male from the original Opitz-Kaveggia family. Moderately
severe mental retardation with behavioral abnormalities was
present in all males old enough for cognitive assessment. Partial or
complete absence of the corpus callosum was noted in all six cases
in which brain imaging was available, and congenital hypotonia was
noted in all but one case. High prominent forehead and small, low set,
simple ears were the most consistent craniofacial manifestations. Only
one individual had macrocephaly (OFC >97 th centile), although the occipitofrontal
circumference centile was greater than the height centile
in 7 of 9 cases. Imperforate anus and wide flat thumbs and great toes
were present in 7 of 10 cases. Cryptorchidism, inguinal hernia, cardiac
defects, and short stature were noted in less than half of affected
males. Constipation was noted in 5 of 8 cases, one case had dystonia
of the head and neck, one case had sagittal craniosynostosis, and one
case had duplicated great toes with a split right hand. Hyperactivity,
affability, and excessive talkativeness were frequent manifestations,
along with socially-oriented, attention-seeking behaviors.
P0109. Fibrous Dysplasia: report of two portuguese patients
A. M. Fortuna1 , J. Silva1 , M. Barbosa1 , M. Gonçalves2 ;
1 2 Instituto Genetica Medica, Porto, Portugal, Hospital Pedro Hispano, Porto,
Portugal.
Fibrous Dysplasia (McCune-Albright syndrome #MIM 174800), of
bone is characterized by the replacement of bone by dysplastic fibrous
tissue. It is classified on the basis of whether the lesions involve one
bone or more than one bone. The cutaneous lesions consist of brown
flat patches of pigmentation that follow an irregular contour. Sexual
precocity and hyperthyroidism are common features. The condition is
mostly sporadic and usually results from postzygotic activating mutations
in GNAS1.
We present a short review of the McCune-Albright syndrome and two
clinical cases of patients with the clinical diagnosis of this syndrome
from our genetic clinic.
Patient 1, a female, age 17, with vaginal bleeding at age 3, and at
present time with one café-au-lait spot in the dorsal region respecting
the midline and polyostotic fibrous dysplasia affecting the skull causing
facial asymmetry and the long bones of the four members, with
more expressive lesion near the right knee. Patient 2 is a male, age
31, presented at age 25 an expansive and suggestive lesion of two left