2009 Vienna - European Society of Human Genetics

Clinical genetics and Dysmorphology
The incidence in Western Europe has been recently reevaluated to
2.7 per million. The main clinical features are progressive cachectic
dwarfism, mental retardation with cerebral leukodystrophy, microcephaly,
progressive pigmentary retinopathy, neurosensorial deafness and
photosensitivity. CS is caused by mutations in ERCC8 (at 5q12) for
CSA and in the ERCC6 genes (at 10q11) for CSB with no genotype/
phenotype correlations so far. However other genes like XPB, XPD,
XPG are causative.
Caries are considered as a minor diagnostic criteria by Nance and
Berry, 1992. Other orodental features like delayed deciduous teeth
eruption, malocclusion, absent/hypoplastic teeth are also described in
the literature.
The aim of the present study, was to investigate the orodental findings
in a series of 10 CS patients included within the PHRC 2005
“Clinical and Molecular study of Cockayne syndrome”. The phenotype
was documented using the D[4]/phenodent registry (www.phenodent.
org). Anomalies of teeth number (missing teeth), shape, structure with
enamel hypoplasia, eruption and position (crowding) were found. The
dental caries diagnostic criteria was correlated to the presence of large
enamel defects prominent in severely affected patients and the subsequent
difficulties in maintaining appropriate oral hygiene. Cephalometric
data and analysis demonstrate a transverse hypodevelopment of
the craniofacial region as well as a class II skeletal profile with vertical
growth and posterior rotation of the mandible inducing an increase of
the lower face height and a retrusive chin. No specific genotype/phenotype
correlations were elicited.
P02.023
cockayne syndrom, case Report
F. Hadipour, Z. Hadipour, Y. Shafeghati;
Medical Genetics Department, Sarem Woman Hospital, Tehran, Islamic Republic
of Iran.
Back ground: Cockayne syndrome is a very rare genetic disorder with
a recessive autosomal inheritance characterized by dwarfism, microcephaly,
mental retardation, deafness, a photosensive dermatitis and
a peculiar form of retinal pigmentation..
Case report: We report a case of cockayne syndrome in four year old
Iranian female child. She was born of a nonconsanguinous marriage.
She is mental retard and dysmorphic, Cachexia (height and weight
both were below the 5 th percentile).
She has failure to thrive, short staure, premature aging, microcephally,
dysarthic speech , photosensivity, and sunken eyes, dental caries.
There was no blindness or deafness, and the fundus examination was
showed Tape to Retinal degeneration. The karyotype was normal .Metabolic
screening was normal.The Radiologic examanination (x- ray)
was showed biconvex flattening of vertebrae and kyphosis.The results
of DNA- repair analysis is strongly reduced DNA- synthesis after UV
indicates Cockaynes syndrome in this patient.
P02.024
Fourth case of cerebral, Ocular, Dental, Auricular, skeletal
syndrome (cODAs), description of new features and molecular
analysis
S. Marlin1 , H. Ducou Le Pointe1 , M. Le Merrer2 , M. Portnoï1 , S. Chantot1 , A.
Mantel3 , J. Siffroi1 , N. Garabedian1 , F. Denoyelle1 ;
1 2 Hôpital Armand Trousseau, Paris, France, Hôpital Necker, Paris, France,
3Hôpital, Kremlin Bicêtre, France.
Cerebral, Ocular, Dental, Auricular, Skeletal Syndrome (CODAS, MIM
600373) syndrome is a very rare congenital malformation syndrome.
This clinical entity is highly distinctive with mental retardation, cataract,
enamel anomalies, malformations of the helix, epiphyseal and vertebral
malformations and characteristic dysmorphic features. To date,
three affected children have been reported since 1991. The aetiology
and pattern of inheritance of CODAS syndrome is still unknown. We
report a new sporadic case presenting with all the characteristic features
of CODAS syndrome associated with undescribed malformations
including heart, laryngeal and liver malformations. All investigations
such as karyotype, metabolic screening and CGH array were normal.
We discuss and investigate differential diagnosis.
P02.025
mLPA analysis detects an high percentage of mutated alleles in
patients affected by cohen syndrome
V. Parri 1 , E. Katzaki 1 , V. Uliana 1 , F. Scionti 1 , I. Longo 1 , R. Vijzelaar 2 , R. Boschloo
2 , A. Selicorni 3 , F. Brancati 4 , B. Dallapiccola 4,5 , L. Zelante 6 , C. P. Hamel 7 , S.
R. Lalani 8 , R. Grasso 9 , S. Buoni 10 , F. Mari 1 , A. Renieri 1 ;
1 Medical Genetics, University of Siena, Siena, Italy, 2 MRC Holland, Amsterdam,
The Netherlands, 3 Pediatric Unit, University of Milan, Milan, Italy, 4 IRCSS
CSS, Mendel Institute, Rome, Italy, 5 Department of Experimental Medicine and
Pathology, La Sapienza University, Rome, Italy, 6 IRCSS CSS, S. Giovanni Rotondo,
Italy, 7 Centre Hospitalier Régional et Universitaire, Centre de Référence
Maladies Sensorielles Génétiques, Montpellier, France, 8 Department of Molecular
and Human Genetics, Baylor College of Medicine, Houston, TX, United
States, 9 IRCSS MEDEA, Bosisio Parini, Lecco, Italy, 10 Child Neuropsychiatric
Unit, University of Siena, Siena, Italy.
Cohen syndrome is a rare autosomal recessive disorder with variability
in the clinical manifestations. It is characterized by mental retardation,
postnatal microcephaly, facial dysmorphisms, ocular abnormalities,
and intermittent neutropenia. Mutations in the COH1 gene have been
found in patients with Cohen syndrome from different ethnic origins.
In a cohort of 19 patients, we previously identified 11 mutations by the
combined use of DHPLC, sequencing analysis and Real Time PCR
probes covering the entire length of COH1 gene (Katzaki E, 2007
J.Hum.Genet. and unpublished data). The use of an MLPA probemix
for COH1 was crucial in identifying missing mutated alleles and in
defining the extension of the rearrangements. Thus, we were able to
identify the second mutated allele in 2 unrelated patients and in 2 affected
sisters. We also found 2 intragenic duplications spanning from
exons 4 to 13 and from exons 21 to 29, respectively. This is the first
time that duplications are reported in Cohen syndrome patients. MLPA
was also implemental in defining the extent of 4 deletions already detected
by Real Time PCR. Although in our small cohort of patients, we
can consider that MLPA is able to detect 24% of mutated alleles. In
conclusion, MLPA demonstrated to be an essential tool for the detection
of microdeletions/microduplications within the COH1 gene at relatively
low cost. For this reason we consider that it could be used as an
initial screening method for the molecular analysis of patients affected
by Cohen syndrome.
P02.026
Amelogenesis imperfecta and cone Rod Dystrophy cORD
A. M. Bloch-Zupan 1,2 , A. J. Mighell 3,4 , D. A. Parry 4 , W. El-Sayed 3 , R. C. Shore 3 ,
I. K. Jalili 4 , M. Michaelides 5 , A. T. Moore 5 , C. F. Inglehearn 4 , H. Dollfus 6 ;
1 Faculty of Dentistry, University of Strasbourg, Strasbourg, France, 2 Reference
Centre for OroDental Manifestations of Rare Diseases, Hôpitaux Universitaires
de Strasbourg, Strasbourg, France, 3 Leeds Dental Institute, Leeds, United
Kingdom, 4 Leeds Institute of Molecular Medicine, University of Leeds, Leeds,
United Kingdom, 5 Institute of Ophthalmology UCL, London, United Kingdom,
6 Centre de reference pour les affections ophtalmiques héréditaires CARGO,
Hôpitaux Universitaires de Strasbourg; Avenir INSERM, Strasbourg, France.
The recessively inherited association of CORD with amelogenesis imperfecta
(AI) or Jalili syndrome (OMIM 217080) was first reported in
a large consanguineous Arabic family from the Gaza strip (Jalili and
Smith, J Med Genet. 1988;25:738-740). Recently the causative gene
CNNM4 (2q11), encoding a putative metal transporter, has been identified
in a pooled cohort of 7 unrelated families. We report and compare
here the orodental phenotype, analyzed using the Diagnosing Dental
Defects Database D[4]/phenodent system, in 4 individuals belonging to
2 distinct pedigrees: a two generation Kosovan family (1) and a Turkish
family (2). The identified mutations were c1312dupC; Leu438ProfsX9
(1) and c.586T>C; Ser196Pro (2).
The retinal dystrophy was of early-onset, presenting in the first few
years of life with photophobia and nystagmus. Visual acuity was severely
reduced in childhood and there was complete absence of color
vision. The dental phenotype co-segregating with the CORD was
that of hypoplastic/hypomineralised AI affecting both the primary and
permanent dentitions. The teeth looked dysplastic and yellow/brown
with almost no visible enamel leading to severe teeth erosion/abrasion.
Radiographic examination revealed absence of distinct contrast
between enamel and dentine, taurodontic first permanent molars and
root formation anomalies. Dentin formation seems also to be altered
with the following defects (intrapulpal calcification of primary molars,
bulbous appearance of permanent teeth crowns, thin roots). Strikingly