2009 Vienna - European Society of Human Genetics

Clinical genetics and Dysmorphology
P02.018
cherubism- case report‘
F. F. Cionca1 , L. Cionca2 , C. Vizitiu2 , C. Ardeleanu1 ;
1 ”Victor Babes” National Institute for Research and Development in Pathology
and Biomedical Sciences, Bucharest, Romania, 2 ”Prof. Dr. Dan Teodorescu”
Clinical Hospital of Oro-Maxilo-Facial Surgery, Bucharest, Romania.
Introduction: Cherubism is a rare autosomal dominant inherited disease
with variable penetrance and expressivity, characterized by a benign
self-limited bone dysplasia of almost exclusively the lower and the
upper jaw. Patients present bilateral, painless, generally symmetrical
swelling of the jaws, caused by the replacement of normal bone with
pseudocystic osteolytic lesions. The disease affects pediatric population,
frequently below five years of age, with slow progression of the
lesions until puberty, followed by their gradual remission in early adulthood,
with rare cases of residual jaw deformity. The diagnosis implicates
clinical findings, associated with radiographic and histological
manifestations, and is confirmed by the molecular genetic testing of
SH3BP2 gene, located on 4p16.3 and affected by mutations in 80% of
the patients with cherubism.
Case presentation: A 9 years old girl presented with mild, bilateral,
progressive, painless and a little asymmetrical enlargement of the
mandible. There were no other clinical findings in physical examination
excepting abnormal teeth implantation on the lower jaw. Radiological
examination revealed bilateral multicystic lesions of the lower jaw and
abnormal teeth implantation. Histological examination demonstrated
the presence of numerous multinucleated acidophilic giant cells randomly
distributed in a fibrovascular stroma of mononuclear spindleshaped
cells. Family history identified no other members with similar
lesions.
Conclusion: Clinical findings and radiographic and histological aspects
of this case plead for the diagnosis of cherubism. In the future, the patient
will require molecular genetic testing for confirming the diagnosis,
long -term follow-up and treatment of manifestations if necessary.
P02.019
Reno-urinary anomalies and ciliopathies: a new approach
c. daescu 1,2 , i. maris 1,2 , i. sabau 1,2 , c. duncescu 2 , a. chirita-emandi 2 , i. simedrea
1,2 , m. puiu 1 , t. marcovici 1,2 , a. craciun 1,2 , o. belei 1,2 ;
1 “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania,
2 “Louis Turcanu” Emergency Hospital for Children, Timisoara, Romania.
Introduction: In the last ten years there has been significant breakthrough
in understanding cilia and the pathology associated with cilia
malfunction. Objective: The authors present 10 cases with reno-urinary
anomalies which we believe are ciliopathies. Material: 10 patients
with anomalies of the renal system admitted in our clinic, Nephrology
Department between 01 January 2006 - 31 Dec 2008, median age was
8.9+/-7.12 years (range 1.5 to 20 years), 5 girls and 5 boys. Method:
In order to establish the diagnosis we used the following imaging studies:
renal and bladder ultrasonography, intravenous urography, voiding
cystourethrography, magnetic resonance imaging. Results: 6 patients
were diagnosed with polycystic kidney disease, 2 of them suffered
nephrectomies, 3 developed renal failure and 1 presented recurrent
respiratory infections (bronchiolitis). 3 patients have neural tube defects
associated with urinary anomalies and 2 of them developed renal
failure. 1 case associated situs inversus, hydrocephaly and vesicoureteral
reflux. Discussions: Half of these children present renal failure,
one girl deceased because of renal failure complications. The quality
of life of the three adolescents with neural tube defects is poor. Conclusions:
It is important to recognize and if it’s possible to genetically
diagnose ciliopathies for a better management and for improving the
quality of life of these children
P02.020
the msX1 allele 4 homozygous child exposed to smoking at
periconception is most sensitive in developing nonsyndromic
orofacial clefts.
M. H. van den Boogaard 1 , D. de Costa 1,2 , I. P. C. Krapels 3 , F. Liu 4 , C. van
Duijn 4 , R. J. Sinke 1 , D. Lindhout 1 , R. P. M. Steegers-Theunissen 4 ;
1 University Medical Center Utrecht, Utrecht, The Netherlands, 2 Erasmus MC,
University Medical Center, Rotterdam, The Netherlands, 3 Academic Hospital
Maastricht, 6202AZ Maastricht, The Netherlands, 4 Erasmus MC, University
Medical Center Rotterdam, Rotterdam, The Netherlands.
Nonsyndromic orofacial clefts (OFC) are common birth defects caused
by certain genes interacting with environmental factors. Mutations and
association studies indicate that the homeobox gene MSX1 plays a
role in human clefting. In a Dutch case-control triad study (mother,
father, and child), we investigated interactions between MSX1 and the
parents’ periconceptional lifestyle in relation to the risk of OFC in their
offspring. We studied 181 case- and 132 control mothers, 155 case-
and 121 control fathers, and 176 case- and 146 control children, in
which there were 107 case triads and 66 control triads. Univariable
and multivariable logistic regression analyses were applied, and odds
ratios (OR), 95% confidence intervals (CI) were calculated. Allele 4
of the CA marker in the MSX1 gene, consisting of nine CA repeats,
was the most common allele in both the case and control triads. Significant
interactions were observed between allele 4 homozygosity of
the child with maternal smoking (OR 2.7, 95% CI 1.1-6.6) and with
smoking by both parents (OR 4.9, 95% CI 1.4-18.0). Allele 4 homozygosity
in the mother and smoking showed a risk estimate of OR 3.2
(95% CI 1.1-9.0). If allele 4 homozygous mothers did not take daily
folic acid supplements in the recommended periconceptional period,
this also increased the risk of OFC for their offspring (OR 2.8, 95% CI
1.1-6.7). Our findings show that, in the Dutch population, periconceptional
smoking by both parents interacts with a specific allelic variant of
MSX1 to significantly increase OFC risk for their offspring. The article
has been published in Hum Genet. 2008 Dec;124(5):525-34.
P02.021
A new case of early-onset cockayne/cOFs syndrome in a
spanish child with mutations in the CSB gene.
B. Gener 1 , A. García 2 , C. Dalloz 3 , F. Sauvanaud 3 , A. Sarasin 4 , D. Pham 4 , V.
Laugel 3 ;
1 Clinical Genetics-Pediatric Department. Hospital de Cruces, Baracaldo, Spain,
2 Neuropediatrics Unit. Pediatrics Department.Hospital de Cruces, Baracaldo,
Spain, 3 Laboratory of Medical Genetics. Faculte de Medecine, Strasbourg,
France, 4 FRE 2939.Institut Gustave Roussy, Villejuif, France.
Cockayne syndrome (CS) is a severe neurodegenerative condition
with multisystemic involvement which belongs to the family of DNA
repair and transcription disorders. Cerebro-oculo-facio-skeletal syndrome
(COFS) has been proved to be allelic to CS but a very limited
number of COFS cases have been clarified at the molecular level so
far. We report on a 20-month-old female, second child of a healthy and
non consanguineous family. IUGR was evident at 30 wks of gestation.
The patient was born at term. She had severe congenital microcephaly
and developed failure to thrive soon after birth. She had bilateral
microphtalmia and congenital cataract. Clenched fingers and lower
limbs rigidity were observed. Bone X-Ray showed mild platyspondyly.
Her neurological development is severely retarded. She has bilateral
neurosensorial deafness. Brain CT scan and MRI were normal at 4
months of age. No retinopathy is present. Extensive metabolic survey
and congenital infections were ruled out. In this context, minor senilelike
dysmorphic features and the presence of photosensitivity suggested
the diagnosis of CS at the age of 13 months. In accordance with the
clinical picture the studies on skin fibroblasts of the recovery of RNA
synthesis after UV exposure showed a high deficiency and two different
mutations in CSB gene (p.Leu871Pro and p.Lys1172X) were found
in this patient. Very few patients have been described worldwide with
these particular mutations. In our opinion this case shares similarities
with CS and COFS, confirming that both entities should be considered
as different parts of the same clinical spectrum.
P02.022
craniofacial and Orodental Features and Phenotype/Genotype
correlations in cockayne syndrome
M. Rousseaux 1 , M. Schmittbuhl 1,2 , R. Mathis 1,2 , M. Koob 3 , H. Dollfus 4,5 , C. Dalloz
5 , V. Laugel 4,5 , A. M. Bloch-Zupan 1,2 ;
1 Faculty of Dentistry, University of Strasbourg, Strasbourg, France, 2 Reference
Centre for Orodental Manifestations of Rare Diseases, Hopitaux Universitaires
de Strasbourg, Strasbourg, France, 3 Department of Radiology, Hôpitaux Universitaires
de Strasbourg, Strasbourg, France, 4 Department of Medical Genetics,
Hôpitaux Universitaires de Strasbourg, Strasbourg, France, 5 Laboratory of
Medical Genetics, EA 3949, Faculty of Medicine, Strasbourg, France.
Cockayne Syndrome is a rare autosomal recessive neurological disease
caused by defects in DNA repair via nucleotide excision repair.