2009 Vienna - European Society of Human Genetics

Clinical genetics and Dysmorphology
P02.149
A chest tumor in a child with Rubinstein taybi syndrome - case
report
O. D. Marginean, Tamara Marcovici, Ioan Simedrea, Maria Puiu, IlieRodica;
1 Ist Pediatric Clinic, Timisoara, Romania.
Background : Rubinstein Taybi is a rare syndrome caused by genetic
defect.
Matherial and method: D.I, 4 years old, female patient, with particular
phenotype, admitted in our hospital in may 2004, for poliarticular
arthritis.She followed clinical examination, and analisis (blood count,
ESR, rheumathoid factor, immunoglobulins, cariotype, bacteriological
analisis from blood, throut , nose, urine ), NPI, ophtalmological and xray
exams, MRI. was perform.
Results and discutions: The child was diagnosed with Rubinstein-Taybi
syndrome [by facial anormalities, specific digital anormalities, growth
retardation (> 3 SD) and mental retardation, genetic defect on 16p13 ]
and oligoarthritis negative RF. Under steroid therapy the arthritis evolution
was well but the child get a right paracardiac pneumonia - treated
13 days with third generation cephalosporins. The X-ray control exam
shows in a right paracardiac a small tumor (2/2 cm) confirmed by MRI.
The pathological exam indicates a paravertebral rhabdomysaroma
The girl was transferred in the oncology department and received the
standard protocols. The evolution was good she is in the second grade
at school, and there are no malign relapse signs.
Conclusions : • The Rubinstein Taybi syndrome is rare;
• The diagnosis is made by clinical exams and with association of the
high quality (pro) methaphase genetic exams;
• The association of this syndrome with right paravetebral rhabdomysaroma
and paraneoplasic arthritis is rare.
• There is a great need to have more sophisticated methods for investigating
this syndrome in our department.
P02.150
A series of patients with Rubinstein-taybi syndrome: Review of
clinical features
S. Basaran Yilmaz, E. Yosunkaya, K. Ender, G. S. Güven, M. Seven, A. Yuksel;
Cerrahpasa Medical Faculty, Department of Medical Genetics, Istanbul, Turkey.
Rubinstein Taybi Syndrome (RTS) is a rare disorder, characterised
by distinctive facial features, broad and often angulated thumbs and
great toes, short stature, and moderate to severe mental retardation.
Other frequent symptoms include seizures, hypotonia, hyperreflexia,
microcephaly, frontal bossing, down-slanting palpebral fissures, small
mouth, frontal hair-up sweep, ear abnormalities, micrognathia, heavy
eyebrows, long eyelashes, ptosis, epicanthal folds, strabismus, persistent
fetal finger pads, scoliosis, spina bifida occulta, cryptorchidism,
hirsutism, and capillar hemangioma. Cardiac defects and structural
brain abnormalities have also been occasionally reported.Although
RTS is inherited in an autosomal dominant manner, and clinical variability
is common in this mode of inheritance, we did not observe a
remarkable clinical heterogeneity among our series of patients. Here,
we report the clinical features of five RTS patients and compare them
with the anomalies reported in the literature. Mental retardation, hypotonia,
down-slanting palpebral fissures, small opening of mouth,
hypoplastic alae nasi, ear abnormalities, broad toe and thumbs were
evident in all patients, supporting the previously reported high ratios of
these findings. Additionally, optic disc pallor and chorioretinal atrophy
were detected in one of the present cases. We suspect that these are
novel findings, which have not been described in the clinical picture of
RTS up to date.
P02.151
Recurrence of achondrogenesis type ii within the same family
E. Kurvinen 1 , M. Shois 2 , K. Joost 1 , R. Zordania 1 ;
1 Tallinn Children`s Hospital, Tallinn, Estonia, 2 Fertilitas, Tallinn, Estonia.
Achondrogenesis type II (ACG2) is a lethal dysplastic disorder of the
skeleton caused in most cases by a novel dominant mutation in the
type II collagen gene (COL2A1) which is present in the heterozygous
state. ACG2 is characterized micromelia, absent of ossification in the
vertebral column, sacrum and pubic bones. The trunk is short with
prominent abdomen and hydropic appearance.
We report a family where counsulted patient had had severe scoliosis,
body disproportion with short trunk. Her first pregnancy was termi-
nated due to severe patological findings noted on fetal ultrasound investigation.
Clinical picture and radiological investigations of the fetus
showed typical findings of achondrogenesis type II. Molecular analysis
of genomic DNA extracted from fetal cells (Prof. Geert Mortier,Ghent
University) revealed the heterozygosity for c.2473G>T mutation
(p.Gly825Arg) in the COL2A1 gene.
Ultrasound investigations during the second pregnancy revealed fetal
hygroma, severe micromelia suggesting the recurrence of achondrogenesis
type II within this family.
Clinical and radiological findings in mother are not similar to the skeletal
anomalies present in children.
As the family history is complicated with the disorder which affects the
same organsystem in the mother and siblings we suspect that the different
and milder phenotype in mother is due to the somatic mosaicism
of the mutant COL2A1 gene. The molecular analyses of the parents
DNA are in process in the time of abstract submission.
P02.152
Acro-mandibulofacial dysostosis associated with microcephaly
and mental retardation: a new case
C. Nava 1 , V. Abadie 2 , S. Lyonnet 1 , G. Baujat 1 ;
1 Department of medical genetics, Université Paris Descartes, Necker-Enfants
Malades Hospital, Paris, France, 2 Department of paediatrics, Necker-Enfants
Malades Hospital, Paris, France.
Acro-mandibulofacial dysostosis is a rare and heterogeneous group
of conditions, characterized by variable craniofacial features including
malar hypoplasia, micrognathia, external ears defects and limb
abnormalities. Among them, Nager syndrome (preaxial acrofacial dysostosis)
is the most common. Post-axial acrofacial dysostoses include
close entities such as Miller, Wildervanck-Smith, and Genée-Wiedemann
syndromes. Mandibulofacial dysostosis may be also associated
with slit-foot deformity.
In 2000 and 2006, four Brazilian patients were reported with a characteristic
combination of mandibulofacial dysostosis associated with
marked microcephaly, trigonocephaly, preauricular skin tags, cleft palate
and mental retardation. Preaxial polydactyly was observed in two
cases. All cases showed feeding difficulties, post natal growth retardation,
and severe delay in language development.
We report a further patient with the same association of mandibulofacial
dysostosis, pre and post-natal microcephaly on -4 SD, preauricular
skin tags, large ear lobes and abnormal thumbs. The patient, the first
child of unrelated heathy Caribbean parents, also presented with severe
feeding difficulties and severe delay in language development.
In conjunction with the other reported Brazilian cases, our observation
gives support to a novel original phenotype within the complex group
of mandibulofacial dysostosis. The molecular bases of this condition
remains unknown, as genetics investigations, including CGH arrays
in our patient, were normal. Hitherto, all cases are sporadic and an
autosomal recessive inheritance may be considered based on parental
consanguinity in one Brazilian case; however, de novo dominant
mutation at an autosomal locus cannot be excluded.
P02.153
Larsen syndrome: clinical report of a patient with a new de novo
mutation
G. Soares 1 , M. J. Sá 1 , V. Mendonça 2 , N. Alegrete 3 , S. Robertson 4 , A. M. Fortuna
1 ;
1 Centro de Genética Médica Jacinto de Magalhães, Porto, Portugal, 2 Paediatrics
Department - Hospital São João, Porto, Portugal, 3 Orthopaedics Department
- Hospital São João, Porto, Portugal, 4 Department of Paediatrics and
Child Health, Dunedin School of Medicine, Dunedin, New Zealand.
Introduction: Larsen et al. (1950) described one of the original cases
of this bone dysplasia in a patient that in 1972 had an affected child.
Features of Larsen syndrome (MIM: #150250) are dislocations of large
joints and unusual facies. Characteristic radiologic findings are also
present. Larsen syndrome is inherited in an autosomal dominant manner.
It’s a rare disease, around 100 cases have been published. In
2004 de novo missense mutations in the FLNB gene were described.
Here we report a new heterozygous de novo mutation in a patient with
Larsen syndrome.
Case Report: First and only child of non-consanguineous parents. At
birth, he presented with congenital anomalies: cleft palate, bilateral
clubfoot, camptodactily and arthrogryposis.