2009 Vienna - European Society of Human Genetics

Clinical genetics and Dysmorphology
deep sensation. SCA 8 is caused by an expanded (CTG) trinucleotide
repeat on the chromosome 13. Friedreich’s ataxia (FRDA), the
most common subtype of early onset hereditary (SCA), is an autosomal
recessive neurodegenerative disorder caused by unstable GAA
tri-nucleotide expansions in the first intron of FRDA gene located at
9q13-q21.1 position. Clinical findings are characterized by neurologic
signals and symptoms of the dorsal root ganglia, the posterior columns,
and pyramidal and spinocerebellar tracts
Here we reported a family who was affected by SCA 8, FRDA and
Hemoglobine S. Gait ataxia was the first symptom in index cases,
followed by dysarthria, weaknes in lower distal limbs and decreased
deep sensation and deep tendon reflexes respectively. Cerebral MRI
showed pure cerebellar atrophy in patient. An spinocerebellar ataxia
and HbS were diagnosis on the virtue of family history, neurological
examination and laboratory and genetics studies. Genetic studies disclosed
a mutation on the SCA 8 locus and FRDA. Index case was
homozygot for FRDA (675/775), his morther (normal/775) and father
were heterozygot, (normal/675). In additionaly we determined HbS
trait in some person in family.
Spinocerebellary ataxias are a group of disorders classified according
to associating clinical signs and symptoms. To the best of our knowledge,
this unusual finding has not been reported previously in the literature.
P02.110
tongue anomalies in clinical genetics evaluation - iasi medical
genetics center’s experience
E. Braha, C. Rusu, M. Volosciuc, M. Covic;
University of Medicine and Pharmacy, Iasi, Romania.
Traditionally the oral area receives minimal emphasis in the medical
examination. Tongue birth defects are among the most common
anomalies and require a careful clinical evaluation. The purpose of this
study is to facilitate the clinical diagnosis of a syndrome with tongue
anomaly.
We selected 16 patients (8 boys and 8 girls) from the total patients
evaluated in Iasi medical genetics centre during 5 years (2000 - 2004,
8615 patients). We studied all tongue anomalies according dysmophic
terms defined by Carey JC et al, 2009. We selected those anomalies
with a high power to suggest the diagnosis (evocative anomalies):
macroglossia, lobulated tongue, microglossia/ hypoglossia; bifid
tongue, asymmetric tongue, tongue fasciculation. We observe the
preponderance of following traits: macroglossia (10 cases - 62.5%),
Microglossia (2), Lobulated tongue (1), bifid tongue (1), asymmetric
tongue (1), tongue fasciculation (1). The syndromes diagnosed were:
congenital hypothyroidism (7 cases), Down syndrome (1), hypoglossia-hypodactylia
spectrum (3), MEN IIB (1), Opitz G/BBB (1), Werdnig
Hoffmann (1) and multiple anomalies (2). The tongue anomalies were
diagnosed after 2 months age old because of the tongue role in mastication,
deglutition, speech etc. The small number of cases could be
explained by the low frequency of the anomalies or by messing the
diagnosis owing to a facile clinical evaluation.
For accurate assessment, correct diagnosis, and management, the
patients should be dealt with in a team approach. When the genetic
tests are budget limited a clinical proper diagnosis is essential to initiate
the correct treatment and genetic counseling.
P02.111
Tracheoesophageal fistula is not significantly associated with
intestinal malrotation - a study based on the Glasgow Register
of congenital Anomalies and NorcAs database
S. K. Munir;
Western Infirmary (NHS Greater Glasgow & Clyde), Glasgow, United Kingdom.
Numerous and large epidemiological studies have been undertaken
of tracheoesophageal fistula (TOF). Only a single study has been
published specifically looking at the epidemiology of intestinal malrotation
(Forrester and Merz,2003). The Glasgow Register of Congenital
Anomalies was used to study anomalies associated with cases
of intestinal malrotation in babies born between 1997 and 2005 (30
cases, 15 syndromic) in Glasgow,UK, and findings were compared
with a previous study (157 cases, 70 syndromic) (Munir S, Muneer A,
Intestinal malrotation and Hedgehog signaling defects - an epidemiologic
study based on the NorCAS database and London Dysmorphology
Database.[Abstract 631]. Presented at the annual meeting of the
American Society of Human Genetics, Oct 26,2007).
Only 2 cases of TOF (2.8%) were seen in the NorCAS study and none
in the current study or in Forrester and Merz’s study. Moreover, while
17 cases (27%) of syndromic malrotation in the NorCAS study had
features of VACTERL, and 2 cases (13%) in the current study, and 2
cases in Forrester and Merz’s study, none of them exhibited TOF.
Mutant mouse models with Hedgehog signaling defects exhibit intestinal
malrotation and features of VACTERL, including TOF. Whilst it has
yet to be seen whether and what proportion of humans with malrotation
and VACTERL have Hedgehog signaling defects, the striking absence
of TOF from VACTERL in cases of syndromic intestinal malrotation as
seen in these studies, and virtual absence of TOF in known hedgehogopathies
such as Pallister-Hall Syndrome, merits further investigation
for differences between hedgehog signaling in mice and humans.
P02.112
Familial congenital unilateral cerebral ventriculomegaly:
Delineation of a distinct genetic disorder
M. S. Zaki 1 , H. H. Afifi 1 , A. J. Barkovich 2 , J. G. Gleeson 3 ;
1 National Research Centre, Cairo, Egypt, 2 (2) Section of Neuroradiology,
Department of Radiology, University of California, San Francisco, CA, United
States, 3 (3) Neurogenetics Laboratory, Howard Hughes Medical Institute, Department
of Neurosciences, University of California, San Diego, CA, United
States.
We identified 2 female siblings, derived from healthy first cousin parents,
with congenital unilateral cerebral ventriculomegaly detected
prenatally. Patient 1 underwent ventriculoperitoneal shunt operation at
1 week old, while patient 2 was followed without surgical intervention.
Both patients presented with mild developmental delay and hemiparesis
contralateral to the involved hemisphere. Focal seizures were
observed in patient 1, whose neuroimaging revealed posterior insular
polymicrogyria in the normal sized ventricle hemisphere and retrocerebellar
cyst. Both siblings displayed near absence of white matter with
marked thinning of the overlying cortex in the affected hemisphere and
very thin corpus callosum. Investigations revealed no other system
involvement and karyotyping was normal. Normal TORCH screening
in subsequent pregnancies, normal parental coagulation profile and
undetectable maternal autoantibodies suggested against the possible
role of extrinsic factors as an etiological factor for unilateral ventriculomegaly.
Parents had normal brain imaging findings. To our knowledge,
unilateral ventriculomegaly has never been reported with familial
clustering. We suggest delineation of a distinct developmental brain
defect, most likely of autosomal recessive inheritance.
P02.113
clinicil genetic analysis of non system vasculitis of small
vessels in children.
E. Voronina 1 , N. Sokolova 2 , L. Zhukova 1 , M. Bogdanova 3 , V. Chasnyk 1 , A.
Harchev 1 , V. Larionova 3 ;
1 St. Petersburg State Pediatric Medical Academy, St. Petersburg, Russian
Federation., St. Petersburg, Russian Federation, 2 Children municipal hospital
N 1, St. Petersburg, Russian Federation., St. Petersburg, Russian Federation,
3 Laboratory of molecular diagnostics of the Research Center at St. Petersburg
State Pediatric Medical Academy, St. Petersburg, Russian Federation., St.
Petersburg, Russian Federation.
Currently there are no any known specific markers for differential diagnostics
of the majority of vasculites.
Objective: to identify the most informative traits, with the aim to facilitate
classification in two groups vasculites of small vessels in children.
Patients And Methods: 80 children with vasculites of small vessels
aged from 3 to 17 years. Among them, 46 patients suffered from system
vasculitis (purples of Shenlejna-Genoh, PSG) and 34 suffered
from non system vasculitis (purples of Schamberg, PS). Control group
included 144 healthy individuals. Diagnoses were verified by clinical,
laboratory and morphological methods (skin biopsy). 4a/4b, T-786C,
G894T polymorphisms of the gene of endothelial NO synthase (eNOS)
were studied by standard methods.
Results: Two distinct forms of PS were identified: sharp cyclic clinical
course in 12 patients (36 %) and chronic recurrent course in 22
patients (64 %).
Hemosiderin in skin biopsy was found in 5 patients with the sharp
course of the disease and in 6 patients with the chronic form of PS. aa
genotype of 4a/4b polymorphism was found more often in patients with