2009 Vienna - European Society of Human Genetics

Clinical genetics and Dysmorphology
the amelogenesis imperfecta appearance is similar in all examined
patients and could be considered as a real diagnostic marker for this
rare disease.
P02.027
congenital ichthyosis - case study
A. Manea1,2 , M. Boia3 , D. Iacob1 , C. Budisan1 , M. Dima1 ;
1University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania,
2Clinical Emergency Hospital for Children “L. Turcanu”, Timisoara, Romania,
3University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania.
Introduction: Congenital Ichthyosis is a rare disorder in medical practice.
It is characterized by a profound thickening of the keratin layer in
fetal skin.
Material and Methods:
We are presenting a case of a premature newborn, female, hospitalized
in our Department at the age of six days.
Results: Clinical and paraclinical examination are leading us to congenital
ichthyosis. From personal history we found out the gestational
age of 37 weeks, birth weight of 2430 g, Apgar score 7, born through
cesarean section, oligoamnios. Mother presented urinary tract infection
during the pregnancy, fever at 5 month of pregnancy.
Clinical examination emphasize: dry, fissured teguments, generalized
exfoliation, bilateral ectropion, upper and lower limbs with retractions
at the level of fingers, finger lypoplasia at the level of lower limbs.
There were monitorized urea, serum protein level, levels of creatinine,
hemoglobin , serum electrolyte, WBC count, blood cultures. Skin cultures
was positive with E. Coli with favorable evolution under antibiotic
therapy. Transfontanelar ultrasonography revealed a picture of intrauterine
chronic affection.
Conclusions: There is a high risk of systemic infection in congenital
ichthyosis; this is the main cause of death.
Under the set therapy the evolution was slowly favorable.
Congenital Ichthyosis is a rare disorder in medical practice and needs
cooperation between neonatologist, dermatologist and medical geneticist.
P02.028
Clinical findings, MR imagings and cytogenetic studies in a
series of 45 corpus callosum dysgenesis patients, born to
consanguineous parents
A. Yuksel, E. Karaca, E. Yosunkaya, S. Basaran Yılmaz, G. S. Güven, M.
Seven;
Istanbul University, Cerrahpasa Medical Faculty, Department of Medical Genetics,
Istanbul, Turkey.
We report 45 corpus callosum dysgenesis patients (from 42 families),
born to consanguineous parents. These patients were referred to our
clinic because of neurodevelopmental delay and/or multiple congenital
anomalies. We classified the patients according to their clinical picture
(facial dysmorphism, cognitive functions, seizures..etc ), cranial MRI,
and cytogenetic findings. Among 45 patients, 4 had total agenesis of
corpus callosum, and the rest had hypogenesis or hypoplasia of corpus
callosum. Addition to collasal dysgenesis, cranial MR imaging of
the patients revealed periventricular leukomalasia, delayed myelinisation,
gray matter pathologies (eg. pacygyria, heterotropia), Dandy
Walker malformation and encephalomalasia. All patiens had neurodevelopmental
delay or mental retardation, and nearly half of them
had seizures. Cytogenetic studies revealed 46,XY,+(21q) karyotype in
one patient with corpus callosum agenesis, characterized by epileptic
seizures and he also had severe neurodevelopmental delay. As genetic
etiology of corpus callosum dysgenesis is not clear, categorizing
patients according to genotype and phenotype, would greatly help
in research studies for etiological background. We conclude that this
categorisition would probably lead to further genetical studies, such
as array CGH and linkage analysis, ultimately aiding in finding out the
responsible gene(s), and genetic mechanisms underlying corpus callosum
dysgenesis.
P02.029
congenital craniolacunia without any associated developmental
defect
B. Tumiene 1,2 , N. Drazdiene 3 , V. Kucinskas 1,2 , B. Dallapiccola 4 ;
1 Department of Human and Medical Genetics, Faculty of Medicine, Vilnius
University, Vilnius, Lithuania, 2 Centre for Medical Genetics, Vilnius University
Hospital Santariskiu Clinics, Vilnius, Lithuania, 3 Centre for Neonatology, Vilnius
University Children’s Hospital, Vilnius, Lithuania, 4 Department of Experimental
Medicine, “Sapienza” University, Mendel Institute, Rome, Italy.
Congenital craniolacunia is a rare calvarial ossification defect characterized
by multiple,‘soap-bubble’ areas of bone rarefactions, resulting
in the faulty impression of abnormal calvarial openings. Lacunar skull
develops during fetal life, becomes manifest at birth, and usually disappears
by the 5th month of postnatal life. The mechanism underlying
craniolacunia is only partially understood, and it is generally related
to dysplastic bone formation associated with focal dural defects. Craniolacunia
can occur in patients with spinal or cranial dysraphism and
Arnold-Chiari malformation type II. Only a few cases of isolated craniolacunia
have been reported.
We investigated a 6-month-old male born to healthy parents of Lithuanian
origin. He was born at term of an uneventful pregnancy. Mild
cranial asymmetry was noticed at birth prompting to an X-ray, which
disclosed pronounced lacunar skull defects in the absence of any associated
additional anomaly. Plain X-rays of the whole skeleton, neurosonoscopic,
cardiosonoscopic, abdominal sonoscopic, ocular fundus
evaluation were unremarkable. Psychomotor development was
normal and craniolacunia was vanishing by 6 months of life.
In conclusion, isolated congenital craniolacunia is considered a rare
calvarial ossification defect. However, since this defect dissapears with
age it is likely overlooked.
P02.030
mixed maternal iso- and Hetero-disomy for chromosome 7
manifesting as Silver-Russell-like phenotype with cystic fibrosis
A. Karalis1 , R. Drouin2 , L. Lands1 , L. Russell1 ;
1 2 McGill University Health Centre, Montreal, QC, Canada, Université de Sherbrooke,
Sherbrooke, QC, Canada.
Maternal UPD7 accounts for 5-10% of cases of Silver-Russell syndrome
(SRS) but is a rare cause of cystic fibrosis (CF). To date, only 5
cases of CF due to matUPD7 have been published. We report a sixth
case that resulted from crossing over, followed by nondisjunction during
meiosis II, resulting in mixed maternal iso- and heterodisomy for
chromosome 7. A one-year-old male child was referred for evaluation
of failure to thrive, global developmental delay and mild hypotonia. The
physical examination revealed features suggestive of Silver-Russell
Syndrome (SRS). Routine investigations yielded normal results, except
for an elevated sweat chloride. Molecular testing demonstrated
that the child was homozygous for the ΔF508 mutation. Parental testing
showed that only the mother carried this mutation. Because of features
suggestive of SRS, testing for UPD 7 was undertaken. Maternal
UPD of the entire chromosome 7 was demonstrated: 32 of 47 microsatellite
markers were informative. No paternal alleles were detected.
Two regions of maternal heterodisomy were identified (7p14.3-pter
and 7q22.1-q22.2) and, and by 9 markers between 7q22.1 and 7q22.2.
The 13 remaining markers were suggestive of maternal isodisomy at
the peri-centromeric region of the short arm (centromere to p14.1) and
both the proximal portion long arm (q11.21 to q21.3) and its terminal
portion (q22.3 to qter). These results are compatible with crossing
over, followed by nondisjunction during meiosis II, resulting in mixed
maternal iso- and heterodisomy for chromosome 7. Isodisomy at the
CFTR locus resulted in homozygosity for the ΔF508 mutation.
P02.031
convergence of molecular genetics and modern cytogenetics in
clinical diagnosis
M. Abdo, E. Edkins;
PathWest, Subiaco, Australia.
Increasingly the scale or resolution of investigations through cytogenetics
and molecular genetics are converging; driven by the elucidation
of more complex rearrangements involved in human disease and the
available technology. Recently the cytogenetics and molecular genetics
departments made changes to clinical practice whereby patients
were screened for several disorders using MLPA, prior to further studies
and / or confirmation using cytogenetics methodologies (primarily
Fluorescent In-Situ Hybridisation). Analysis for a range of disorders
including general screening for microdeletions and duplications across
all chromosomes through to specific deletions associated with phenotypes
such as Smith-Magenis, Cri du Chat and DiGeorge Syndrome
was performed using one or more multiplex probe ligation-dependent
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