2009 Vienna - European Society of Human Genetics

Clinical genetics and Dysmorphology
sessment was carried out at 23.3 weeks of gestation, the study revealed
intrauterine growth restriction, ribs with angle grinding, cleft
hands and bowed femurs. An amniocentesis was performed showing
a normal 46, XY karyotype. Physical examination showed wide fontanels
and sutures, broad face, downslanting palpebral fissures, broad
and depressed nasal bridge, anteverted nares, central cleft palate, microretrognathia
and rotated and low implanted ears. Short neck, hands
with digitalization of thumbs,diastasis between first and second finger
bilaterally, clinodactyly of bilateral fifth fingers and cutaneous syndactyly
between third and fourth fingers with hypoplasic, convex nails. Xrays
of the tubular bones showed bowed humerus, femur and tibia,
both fibulas were small.
Results: Molecular analysis of exon 3 of FLNA gene showed and insertion
at codon 209 that generates a frameshift without causing a
premature stop codon in the patient and his mother and has not been
previously reported.
Discussion: A clinical diagnosis of OPD2 was initially suspected in our
patient based on prenatal and postnatal clinical findings. Clinical evolution
and molecular studies confirmed the disease.
P02.089
spectrum of oral clefts in the light of contemporary research
study
A. Matulevičienė1,2 , L. Ambrozaitytė1,2 , E. Preikšaitienė1 , A. Utkus1,2 , L.
Linkevičienė3,4 , B. Aleksiūnienė1,2 , E. Dagytė1,2 , Ž. Čiuladaitė1,2 , V. Šliužas1,2 , V.
Kučinskas1,2 ;
1Department of Human and Medical Genetics, Faculty of Medicine, Vilnius
University, Vilnius, Lithuania, 2Centre for Medical Genetics, Vilnius University
Hospital Santariškių Klinikos, Vilnius, Lithuania, 3Institute of Odontology, Faculty
of Medicine, Vilnius University, Vilnius, Lithuania, 4Vilnius University Hospital
Žalgirio Klinikos, Vilnius, Lithuania.
Aim. To apply contemporary knowledge in genomics, modern techniques
for experimental testing and data analysis in the investigation
of genetic and genomic basis of oral clefts (OCs) and the acquired
knowledge introduced into the practise of Lithuanian health system.
Material and method. The study group consisted of 250 patients with
OCs and one or more major congenital anomalies. According to syndromologic,
cytogenetic and molecular genetic data analysis were categorized
into two groups: recognized conditions (40.8%, 102 cases)
and unknown origin (59.2 %, 148 cases) during the past decade. The
type of cleft was classified according to ICD-10 and LAHSHAL classifications.
Results. 74 patients had recognized syndromes and sequences (20
different units). One of the most common was Pierre Robin sequence
(32 cases), 6 cases of holoprosencephaly, 5 cases of OFD syndrome,
4 of amniotic band sequences. Among the cases with recognized conditions
28 had chromosomal abnormalities: such as trisomy 13 (16
cases), trisomy 21 (1 case) and trisomy 18 (1 case), others were partial
trisomies (46, XY, rec(14) dup(14) inv(14)(p11.2;q32.1); 46, XX, der(1
3)t(13;20)(p11.2;p13)), partial deletions (46,XX, del(18)(q21.32;qter)),
reciprocal translocations (46, XX, t(10;11)(p11.2;q23.3), 46, XX,
t(2;6)(p21;p25), 46, XX, t(8;16)(p21.1;p13.1)) and two mosaic karyotypes
(46, XY [1]/46, XY, r(21) [10]/46, XY, -21, +mar [30]/45, XY, -21
[9] and 47,XX,+mar [17]/46,XX [3]). DNA microarray based on APEX2
technology with 640 SNPs in 43 CLP candidate genes was carried out
for 104 triads.
Conclusion. The obtaining results were relevant to further prophylaxis
of the definite population.
P02.090
search for genomic imbalances in a cohort of 20 patients with
oral-facial-digital syndromes negative for mutations and large
rearrangements in the OFD gene
C. Thauvin-Robinet 1,2 , P. Callier 3 , B. Franco 4,5 , B. Aral 6 , N. Gigot 7 , A. Donzel 7 ,
A. Mosca-Boidron 3 , A. Masurel-Paulet 1,2 , F. Huet 8 , J. Teyssier 6 , F. Mugneret 3 , L.
Faivre 1,2 ;
1 centre de génétique, Dijon, France, 2 Centre de Référence Maladies Rares
- Anomalies du Développement et Syndromes Malformatifs de l’Interrégion Est,
CHU Dijon, Dijon, France, 3 Laboratoire de Cytogénétique, CHU Dijon, Dijon,
France, 4 Telethon Institute of Genetics and Medicine (TIGEM), Napoli, Italy,
5 Medical Genetic Services, Department of Pediatrics, Federico II University
of Naples, Napoli, Italy, 6 Laboratoire de Génétique Moléculaire, CHU Dijon,
Dijon, France, 7 Laboratoire de Génétique Moléculaire, CHU Le Bocage, Dijon,
France, 8 Service de Pédiatrie 1, Hôpital d’Enfants, CHU Dijon, Dijon, France.
Oral-facial-digital syndromes (OFDS) result from the association of
abnormal clinical features affecting almost invariably the face, mouth
and digits. Other organ systems can be involved, defining a complex
nosology including 13 specific subtypes. Some of them have been described
in only one or two reports. Some overlap between subtypes
is suspected. The clarification of this complex nosology could only
come from a better understanding of their molecular bases. However,
only the OFD1 gene responsible for OFD type I is currently known.
Because of the presence of multiple congenital abnormalities (MCA)
and/or mental retardation in some OFDS, we questioned about the
possibility of submicroscopic rearrangements as a cause of OFDS. We
therefore performed high-resolution array-CGH (244 or 105K Agilent)
in a series of 20 OFDS negative for mutations and large rearrangements
in the OFD1 gene, gathered through an international collaboration.
Only seven patients could be assigned to a specific subtype
of OFDS. Three patients had malformations that are not commonly
found in the different OFDS subtypes, including gyration abnormalities,
abnormal lung lobulation, deafness, imperforate anus, and trigonocephaly.
Nine patients had mental retardation. We failed to evidence
submicroscopic chromosomal imbalances in this series. These results
suggest that chromosome imbalances appear rarely involved in OFDS
and that mutations within single genes may be responsible for these
phenotypes. Further work at a molecular level is needed to identify
the causes and allow appropriate counselling for families regarding
specific recurrence risk and prognosis.
P02.091
Confirmatory report of Megarbane autosomal recessive otofacial
syndrome
M. Mathieu 1 , G. Morin 1 , B. Demeer 1 , F. Imestouren-Goudjil 1 , B. Devauchelle 2 ,
C. Kolski 3 , B. Deschepper 4 , T. Attié-Bitach 5 , A. Receveur 6 , H. Copin 6 ;
1 Unité de Génétique Clinique - CHU d’Amiens, Amiens, France, 2 Service de
Chirurgie Maxillo-Faciale - CHU d’Amiens, Amiens, France, 3 Service d’ORL
- CHU d’Amiens, Amiens, France, 4 Service de Radiologie A - CHU d’Amiens,
Amiens, France, 5 Département de Génétique - Hôpital Necker - Enfants Malades,
Paris, France, 6 Laboratoire de Cytogénétique - CHU d’Amiens, Amiens,
France.
In 2005, Megarbane et al reported two sisters from a Libanese consanguineous
family (their parents were first cousins), with a new otofacial
syndrome. These patients presented microcephaly, dysmorphic
features, very dysplastic low-set ears, malformation of the middle ear
and short stature. In addition, one of the patients had a posterior cleft
palate, and the other an oesophageal atresia. Because of the recurrence
in sibs and the parental consanguinity an autosomal recessive
mode of inheritance was suggested.
We report a similar observation concerning an 18-year-old boy. This
patient was the second of three children from non consanguineous
parents. There was no remarkable familial history. He presented a
mandibulo-facial dysostosis with microcephaly, extremely rudimentary
and low-set helix of ears, absence of the external auditory channel,
long nose with low columella, short philtrum, everted lower lip and
small chin. A low implantation of the thumbs, with ankilosis of the right
one, was noticed. The patient also presented a mild mental retardation
and severe conduction deafness. The CT scan revealed hypoplastic
middle ear cavity with absence of aeration and underdeveloped auditory
ossicles. At the age of 18, the microcephaly persisted (-3 SD),
stature was normal (171cm) but stayed inferior to the familial height.
Chromosomal investigations (standard karyotype and array-CGH)
were normal. The molecular screening of the CHD7 gene responsible
of the CHARGE association was negative.
We compare this observation with other known oto-facial syndromes
and especially the familial observation of Megarbane.
P02.092
Phenotypic characterization of PHACE(S) Association, first
italian study based on Eight patients
A. Baban 1,2 , M. Pelegrini 1 , M. T. Divizia 2 , N. Vercellino 1 , L. Bricco 2 , G. Gimelli 2 ,
E. Priolo 3 , A. Rimini 1 , A. Rossi 4 , S. Gimelli 5 , R. Ravazzolo 2,6 , G. Pongiglione 1 , M.
Lerone 2 , P. Dalmonte 1 ;
1 Cardiovascular Department- Gaslini Children Hospital, Genova, Italy, 2 Molecular
and Cytogenetics Unit- Gaslini Children Hospital, Genova, Italy, 3 Ophthalmology
Unit- Gaslini Children Hospital, Genova, Italy, 4 Neuroradiology