2008 Barcelona - European Society of Human Genetics

Clinical genetics
the CL group, while the most common associated anomalies in the
CLP group were musculoskeletal (32 .9%), cardiovascular anomalies
(22 .7%) and anomalies of central nervous system (10 .2%) . There are
also some differences in pairs of associated anomalies with OCs . The
results indicate that CL and CLP could be genetically distinct entities
and should be analyzed separately when possible .
P01.338
Phenotypic diversity of oral-facial-digital syndrome
E. Sukarova-Angelovska, M. Kocova, N. Angelkova, S. Palcevska-Kocevska,
L. Kojic;
Pediatric Clinic, Skopje, The former Yugoslav Republic of Macedonia.
The oral-facial-digital syndromes (OFDS) are variable group of disorders
characterized by malformations in oral cavity, face and digits
on hands and feet . Nine different subgroups are described depending
on the severity of the above mentioned anomalies as well as on
the additional anomalies of the brain, kidneys, limbs, eyes and other
organs . However, overlap between groups occurs frequently in described
cases .
Four patients with different type of oral-facial-digital syndrome (OFD)
have been described . The patients showed variable anomalies on oral
structures, tongue and digits on hands and feet . Anomalies of other
organs and systems were noticed, including brain (1 patient), heart (1
patient) and kidneys (1 patient) . The diagnosis of OFD types I, IV, and
VI (two patients) has been established . Severity of the disease varied
in all of them .
Minor facial anomalies, digital malformations, as well as the existence
of additional malformations of other organs enable classification of the
patients in subgroups. Although there are attempts for classification
according to specific criteria, the diagnosis of the subtype is not always
easy and clear . Many doubtful cases have been reported . The similarity
and diversity of the clinical findings of the above described cases
points out the difficulty in delineation of the subtypes of OFD syndrome
because of the overlapping features between them and with related
syndromes .
P01.339
Randomized dose comparison of pamidronate in children with
types iii and iV Osteogenesis imperfecta: 3 vs 6 month cycles
J. C. Marini 1 , A. A. Obafemi 1,2 , M. K. Abukhaled 1 , H. L. Cintas 3 , J. F. Troendle 4 ,
A. D. Letocha 1 , J. C. Reynolds 5 , S. Paul 3 ;
1 National Institute of Child Health and Human Development, Bethesda, MD,
United States, 2 Clinical Research Training Program-Foundation for NIH and
Pfizer Inc, grant research support, Bethesda, MD, United States, 3 Rehabilitation
Medicine, NIH Clinical Center, Bethesda, MD, United States, 4 Biometry and
Mathematical Statistics Branch, NICHD, NIH, Bethesda, MD, United States,
5 Nuclear Medicine, NIH Clinical Center, Bethesda, MD, United States.
Aim: To determine whether the vertebral benefits of q3m infusion cycles
can be attained on q6m cycles, with a lower cumulative dose .
Methods: Twenty-seven children with types III and IV OI were randomly
assigned to receive 1mg/kg/3d IV pamidronate in q3 or q6 month
cycles . All patients had spine radiographs, L1-L4 DXA, and musculoskeletal
and function testing .
Results: L1-L4 DEXA increased significantly after 1 year of q3m cycles,
with average change in z-score =+1 .41 SD, but did not improve
significantly with further treatment. In the q6m group, the average
change in DEXA was not significant. Repeated measures analysis of
DEXA z-scores yielded a z-score rate change of 0 .064 SD/m for q3 vs
0 .036 SD/m for q6 group (p=0 .13) . T12-L4 vertebral area and central
height were determined from radiographs . Repeated measures analysis
revealed significant improvement of q6m group average LI-L4 and
T12-L2 vertebral height (p=0 .05, 0 .01) and area (p=0 .002, 0 .006) . The
rate of improvement of the q3m and q6m groups did not differ for L1-L4
area or height (p=0 .52, 0 .86) or T12-L2 area or height (p=0 .28, 0 .77) .
The OI children had no significant improvement in fracture incidence,
manual muscle testing or BAMF motor scores in either group . Noteworthy,
response to treatment was highly variable in each treatment
group; improvement in vertebral area did not correlate with change in
DEXA z-score .
Conclusions: Equivalent gains in vertebral height and area are obtained
with q6m and q3m pamidronate cycles . For individual OI children, gain
in DEXA does not correlate with extent of vertebral response .
P01.340
Osteoporosis-Pseudoglioma syndrome in two sisters
G. O. Cetin 1 , F. Duzcan 1 , E. Tepeli 1 , F. S. Kirac 2 ;
1 Pamukkale University School of Medicine, Department of Medical Biology,
Denizli, Turkey, 2 Pamukkale University School of Medicine, Department of
Nuclear Medicine, Denizli, Turkey.
Osteoporosis-Pseudoglioma Syndrome (OPPG) is an autosomal recessive
disorder characterized by congenital blindness and severe
juvenile osteoporosis leading to fragility of long bones . Affected individuals
often have deformed bones due to fractures . The ophthalmologic
findings may include phthisis bulbi, microphthalmia, and some
vitreoretinal changes . The OPPG locus is mapped to 11q12-13 and
mutations that cause OPPG were identified in the LRP5 gene. LRP5
is a member of low density lipoprotein receptors (LDLR) family and a
component of the Wnt pathway . Here, we report two sisters diagnosed
as OPPG who were referred to genetic service with osteogenesis imperfecta,
bilateral congenital nystagmus and microphthalmia . . Their
parents were phenotypically normal first cousins. The older sister was
18 years and the younger was 14 years old . They had congenital blindness
and both had operations due to long bone fractures resulting in
inability to walk. Physical examination findings included microphthalmia,
scleral opacity and skeletal deformities especially in the lower
limbs of both sisters . Tc-99m MDP whole-body scintigraphy showed
deformation and asymmetry of the lower limbs and axial bones of the
older sister while the younger one had normal scintigraphic findings.
Dual-energy X-ray absorptiometry measurements revealed osteoporosis
of both cases. According to these findings OPPG was prediagnosed
and LRP5 gene mutation screening is planned .
P01.341
Overgrowth and X chromosome imbalance: study of two
unrelated females
M. P. Ribate 1 , J. del Valle 2 , I. Bueno 3 , B. Puisac 1 , M. Arnedo 1 , M. C. Gil 1 , J. C.
de Karam 1 , J. Pie 1 , L. A. Pérez-Jurado 2 , F. J. Ramos 1,3 ;
1 University of Zaragoza Medical School, Zaragoza, Spain, 2 University Pompeu i
Fabra, Barcelona, Spain, 3 Hospital Clínico Universitario, Zaragoza, Spain.
In humans, partial X chromosome duplications/deletions are relatively
rare chromosome rearrangements, described predominantly in males
with mental retardation and generally associated with phenotype anomalies
. Nevertheless affected females have also been reported although
most of them do not show abnormal clinical findings, probably due
to skewed, preferential inactivation of dup/del(X) chromosomes, and
subsequent selection against cells with an active abnormal X in carrier
females . However, some females with dup/del(X) chromosomes and
random X-inactivation also exhibit developmental anomalies . Therefore,
females with two X chromosomes and an active duplicated/deleted
segment are functionally disomic/monosomic for genes that are
normally subject to X-inactivation and functionally trisomic/disomic for
those genes that escape X inactivation .
Here, we report on two unrelated females with overgrowth, Sotoslike
phenotype, mental retardation, normal sexual development and
de novo X chromosome anomalies, both originated in the paternal X
chromosome and showed random X-inactivation . Diagnosis was confirmed
by array-CGH and MLPA, and completed by X-inactivation and
microsatellite studies. The first case, a 14 year-old girl with epilepsy
carried a 20.2 Mb Xp duplication (p11.3 → p21.3). The second, a 17
year-old female was found to have a 26 Mb Xq deletion (q24-qter) and
she had idiopathic thrombocytopenic purpura (ITP). These findings
indicate that a gross functional imbalance in the cells with functional
disomy/monosomy due to an active dup(Xp)/del(Xq) chromosome respectively,
may have caused the same effect on prenatal and postnatal
growth in both patients .
P01.342
Vitamin A deficiency in a neonate with PAGOD syndrome
D. Babovic-Vuksanovic, R. Gavrilova, S. Kirmani, A. N. Lteif, T. M. Olson;
Mayo Clinic, Rochester, MN, United States.
PAGOD syndrome is a rare condition characterized by multiple congenital
anomalies . These include pulmonary artery and lung hypoplasia,
agonadism, diaphragmatic abnormalities and congenital cardiac
defects . Omphalocele, various degrees of genital anomalies, cleft palate
and optic nerve hypoplasia have also been described in affected
patients . The etiology of this condition is still unknown . The spectrum of