2008 Barcelona - European Society of Human Genetics

Clinical genetics
characterized by vermis agenesis or hypoplasia, cystic dilation of the
4 th ventricle and a large posterior fossa. The syndrome is defined by
the presence of these three signs . There are three closely associated
types of DWS: DWS malformation, DWS mega cisterna magna and
DWS variant . OBJECTIVE . Presentation and discussion of three cases
with different morphological and clinical forms of DWS . In all three
cases, diagnosis was reached by incorporation of clinical (macrocephaly,
seizures) and imaging (X-ray, CT, MRI) data . RESULTS . Patient
#1 was diagnosed with Dandy-Walker malformation; he has a sister
with Fraser syndrome . Patient #2 was diagnosed with a posterior fossa
arachnoid cyst, left-sided Claude-Bernard-Horner syndrome, congenital
heart disease (coarctation of the aorta, mitral stenosis) and gastroesophageal
reflux. Patient #3 was diagnosed with Dandy-Walker
variant in a rare association with neurofibromatosis. CONCLUSIONS.
DWS is a malformative association of the central nervous system with
variable phenotype; it is frequently associated with other anomalies
and an uncommon familial genetic load .
P01.275
De morsier syndrome - case presentation
M. Boia, A. Manea, E. S. Boia, I. Cioata, D. Iacob, M. Dima;
University of Medicine and Pharmacy Timisoara, Timisoara, Romania.
Introduction: De Morsier syndrome is an extremely rare affection in
medical practice, its diagnosis in the neonate period is exceptional . It is
characterized by association of structural and functional anomalies of
nervous system and endocrine glands (especially hypothalamus and
hypophysis) . The lesions of nervous system can involve optical nerves
with optical nerve atrophy and agenesis of corpus callosum and cavum
septum pellucidum .
Material and method: The presented patient is a girl with age of 6
month, female gender, held in our Clinics’ evidence for prematurity, extreme
hypotonia, agenesis of corpus callosum , nystagmus, eye disorders
. The clinical - biological evolution was poor, with low level regarding
stature and weight and major delay in psyhomotor acquisitions .
Results: Several investigations and biological explorations were done:
cranial ultrasonography - which shows agenesis of corpus callosum ,
stationary hydrocephaly ; MRI: agenesis of corpus callosum, increased
ventricles dimensions .
Oftalmological examination and eye ultrasound shows optical nerve
atrophy . The presence of the early puberty signs (pubic hair ) and
statural deficit are signs of endocrine disorders without being major
modifications of hormonal doses.
Conclusions: Extremely rare affection in pediatric medical practice .
Positive diagnosis is established based on association of major clinical
signs: eye manifestations (optical atrophy, nystagmus) early puberty,
agenesis of corpus callosum , confirmed by specific investigations:
cranial ultrasonography , MRI, specific blood tests..
P01.276
F142L mutation in GJB2 gene in a patient with uncommon skin
disorder and deafness
I. Barisic 1 , I. Sansovic 1 , S. Murat-Susic 2 , R. L. Alford 3 , G. Minarik 4 , F. Barisic 5 ;
1 Children’s University Hospital Zagreb, Zagreb, Croatia, 2 Department of Dermatology,
Clinical Hospital Centre Salata, Zagreb, Croatia, 3 Bobby R. Alford
Department of Otolaryngology-Head and Neck Surgery , Baylor College of,
Huston, TX, United States, 4 Faculty of Natural Sciences, Comenius University,
Bratislava, Slovakia, 5 Health Care Center Zagreb, Zagreb, Croatia.
Dominant mutations in the human GJB2 gene, which encodes connexin
26 (Cx26) can cause non-syndromic hearing loss, but can also
manifest with various skin disorders including palmoplantar keratosis
(PPK), Vohwinkel syndrome, Bart-Pumphrey syndrome (BPS)
and keratitis-ichthyosis-deafness (KID) syndrome . We present a girl
with congenital hearing impairment, plantar keratosis, extensive skin
changes in form of follicular inflammatory papules, and erythematous,
often scaly patches affecting whole body, including scalp and face .
In addition, she had extensive mucosal involvement including oral
and esophageal mucosa and perigenital region . Her hair was sparse
and thin, she had submucosal cleft palate, and hypodontia . No other
abnormalities were observed . Laboratory studies excluded immune/
autoimmune deficiencies. Karyotype and FISH for 22q11.2 microdeletion
were normal . Sequencing of the coding region of the GJB2 gene
revealed a de novo heterozygous F142L mutation located in the third
transmembrane domain of the Cx26 gene . This mutation has been
reported only once, also in a patient with unusual mucocutaneous findings
and deafness. Our patient confirms the pathogenic nature of this
mutation, delineating associated clinical manifestations . It also points
out at the broad and overlapping nature of ectoderm derived tissue
changes due to the autosomal dominant GJB2 mutations .
P01.277
X-linked deafness type 3 (DFN3) phenotype associated with a
paracentric inversion
J. J. MacKenzie 1,2 , K. McKenzie 1,2 , K. K. Brown 3 , C. C. Morton 3,4 , K. J. Harrison
1,2 ;
1 Queen’s University, Kingston, ON, Canada, 2 Kingston General Hospital,
Kingston, ON, Canada, 3 Harvard Medical School, Boston, MA, United States,
4 Brigham and Women’s Hospital, Boston, MA, United States.
We report a 7 year old male with severe sensorineural hearing loss
diagnosed at 8 months . His features included a round face, hypertelorism,
epicanthic folds and a broad nasal root . Initial developmental
concerns resolved once he was in an appropriate educational program
. Sequencing for GJB2 and GJB6, Fragile X testing, echocardiogram,
and abdominal ultrasound were normal . An ECG revealed an
incomplete RBBB . The CT scan revealed a large fundus of the internal
auditory canals and absence of the bony partition between the fundus
and the adjacent cochlear turns with a widened modiolus bilaterally .
Therefore, he was at risk for a fistulous communication between the
subarachnoid space and inner ear resulting in a perilymphatic gusher
upon stapes manipulation. These findings are consistent with those
described in persons with DFN3 hereditary deafness . His karyotype
was 46,inv(X)(q13q24),Y .ish inv(X)(XIST+) . Successive FISH experiments
refined the breakpoints to inv(X)(q21.1q22.3). The Xq21.1
breakpoint was narrowed to a 25 kb region about 450 kb centromeric
to the DFN3 gene, POU3F4. Other DFN3 patients lacking mutations
within POU3F4 have been reported. Ten had deletions centromeric to
POU3F4, one had an inversion and deletion centromeric to POU3F4
and one had a duplication centromeric to POU3F4 and an inversion
including POU3F4 . In the present case there were no detectabale
deletions or duplications near the Xq21 .1 breakpoint . Thus, we hypothesize
that the hearing loss phenotype in this patient is caused
by dysregulation of POU3F4 due to separation from cis-acting regulatory
elements . The patient’s asymptomatic mother had a karyotype of
46,X,inv(X)(q13q24)[19]/45,X[11] .
P01.278
Polymorphisms in the glucocorticoid receptor in children with
difficult bronchial asthma
M. V. Zhdanova, V. S. Tikhoniva, A. N. Voitovich, M. A. Bogdanova, G. A.
Novik, D. S. Korostovcev, V. I. Larionova;
Saint-Petersburg Pediatric Medical Academy, Saint-Petersburg, Russian Federation.
Objective . We investigated allele and genotype frequencies of the BclI
and Tth111I polymorphisms in the glucocorticoid receptor (GR) gene
among children with difficult bronchial asthma.
Patients and methods . Our study group consisted of 59 children (43
boys and 16 girls) in age of 2-17 suffering from difficult asthma and
control group consisted of 151 healthy children (78 boys and 73 girls)
in age of 4-17 . The BclI and Tth111I polymorphisms were detected
by PCR-RFLP using the primers and methods previously described
(Fleury I . et al ., 2003; Van Rossum EFC . et al ., 2004) . Data were compared
through Chi-square test .
Results . Table 1 . Genotype frequencies in asthma patients and controls
Study group (59) Control group (151)
Genotypes boys girls boys girls
43 (72,9%) 16 (27 .1%) 78 (51,7%) 73 (48,3%)
BclI-CC 39,5 % 37,5 % 32% 34,2%
BclI-CG 48,8 % 50 % 51,3% 52,1%
BclI-GG 11,6 % 12,5 % 16,7% 13,7%
Tth111I-CC 36,6 % 37,5 % 47 .4% 49 .3%
Tth111I-CT 56 % 50 % 43 .6% 39 .7%
Tth111I-TT 7,3 % 12,5 % 9 .0% 11 .0%
Conclusion. Allele and genotype distributions of BclI and Tth111I polymorphisms of
the GR gene were similar in asthma patients and controls and previously reported
populations. There were no significant differences in allele and genotype frequencies
in groups of children with different sex.